Non-peptidic somatostatin type 5 receptor agonists and uses thereof

Abstract

Described herein are compounds that are somatostatin modulators, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds to treat conditions, diseases, or conditions that would benefit from modulation of somatostatin activity.

Description

[0001] This application is a divisional application of the Chinese patent application with the application date of August 10, 2020, application number 202080072298.0, and invention name “Non-peptide somatostatin type 5 receptor agonists and their uses” (the application date of the corresponding PCT application is August 10, 2020, and the application number is PCT / US2020 / 045610).

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims the benefit of U.S. Provisional Patent Application No. 62 / 886,764, filed August 14, 2019, which is incorporated herein by reference in its entirety. Technical Field

[0004] Described herein are compounds that are somatostatin modulators, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat conditions, diseases, or disorders that would benefit from modulation of somatostatin activity. Background Art

[0005] Somatostatin is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation by interacting with G protein-coupled somatostatin receptors and inhibiting the release of many secondary hormones. Six subtypes of somatostatin receptor proteins (SSTR1, SSTR2a, SSTR2b, SSTR3, SSTR4, SSTR5) have been identified, which are encoded by five different somatostatin receptor genes. Modulating specific subtypes of somatostatin receptors or combinations thereof is attractive for treating conditions, diseases, or disorders that would benefit from modulation of somatostatin activity. Summary of the Invention

[0006] The compounds described herein are somatostatin modulator compounds. In some embodiments, the compounds described herein modulate one or more of the subtypes of somatostatin receptor proteins. In some embodiments, the compounds described herein modulate a subtype of somatostatin receptor. In some embodiments, the compounds described herein modulate the SST5 receptor. Somatostatin peptide analogs formulated as reservoir injections, such as octreotide, lanreotide, and pasireotide, are conventionally used to normalize hormone levels for the treatment of growth hormone (GH)-secreting adenomas, pancreatic neuroendocrine tumors, and carcinoid tumors. Octreotide is also reportedly used to treat congenital hyperinsulinemia (CHI, sometimes referred to as congenital hyperinsulinemia of infancy, or persistent hyperinsulinemic hypoglycemia of infancy), a condition that causes abnormally high insulin levels in individuals, which in turn leads to frequent episodes of low blood sugar (hypoglycemia). Depot formulations of these peptide drugs are very expensive and require frequent trips to the doctor's office for painful injections, which can lead to injection site reactions. The compounds described herein are structurally distinct molecules from peptide analogs. The compounds described herein are somatostatin modulators that selectively activate somatostatin receptor subtype 5 (SSTR5), which in turn inhibits insulin secretion, promotes glucose release, and also inhibits GH secretion.

[0007] In one aspect, described herein are compounds of formula (I), or a pharmaceutically acceptable salt, or pharmaceutically acceptable solvate thereof:

[0008]

[0009] in:

[0010] Ring A is a carbocyclic ring or a heterocyclic ring;

[0011] X is N or C–R a ; Y is N or C–R b ; Z is N or C–R c ;

[0012] R a 、R b and R c are independently hydrogen, halogen, –CN, –N(R 9 )2. –OR f , –CO2R 9 、–C(=O)N(R 9)2, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 fluoroalkoxy, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted monocyclic carbocycle, or substituted or unsubstituted monocyclic heterocycle;

[0013] R f -L 1 -R g ;

[0014] L 1 is absent, C1-C6 alkylene, C1-C6 fluoroalkylene, or C1-C6 heteroalkylene;

[0015] R g is hydrogen, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, -CO2R 9 、-C(=O)N(R 9 ) 2, or substituted or unsubstituted monocyclic heterocycle;

[0016] R 1 and R 2 are independently hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C6 cycloalkyl, or substituted or unsubstituted C3-C5 heterocycloalkyl;

[0017] R 3 For hydrogen, -CN, –CO2R 9 、–C(=O)N(R 9 )2, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl;

[0018] R 4 and R 5 are independently hydrogen, halogen, –OR 9 ,–N(R 9 )2, –CN, –CO2R 9 、–C(=O)N(R 9 )2, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl;

[0019] R 6is substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C1-C8 fluoroalkyl, substituted or unsubstituted C1-C8 heteroalkyl, or -L 2 -R 6a ;

[0020] L 2 is absent, substituted or unsubstituted C1-C8 alkylene, or -CHR 6b -;

[0021] R 6a is substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted C2-C 10 Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl;

[0022] R 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl;

[0023] R 7 is hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted C2-C 10 Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl;

[0024] or R 6 and R 7 together with the nitrogen to which they are attached, form a substituted or unsubstituted N-containing heterocyclic ring;

[0025] Each R 8 、R 11 and R 12 are independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted monocyclic carbocycle, substituted or unsubstituted monocyclic heterocycle, -CN, -OR 9 、–C(=O)R 10 , –CO2R 9 、–C(=O)N(R 9 )2, –N(R 9 )2, –NR 9 C(=O)R 10 ,–NR 9 C(=O)OR10 ,–NR 9 C(=O)N(R 9 )2, –C(R 9 )=N-OR 9 ,–SR 9 、–S(=O)R 9 ,–SO2R 9 , or –SO2N(R 9 )2;

[0026] or R 11 With adjacent R 8 And R 11 and adjacent R 8 The linked atoms together form a fused substituted or unsubstituted carbocyclic ring, or a fused substituted or unsubstituted heterocyclic ring;

[0027] Each R 9 are independently hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted monocyclic heteroaryl;

[0028] or two R on the same N atom 9 together with the nitrogen atom to which they are attached, form a substituted or unsubstituted N-containing heterocyclic ring;

[0029] Each R 10 are independently substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted monocyclic heteroaryl; and

[0030] n is 0-3.

[0031] Any combination of the groups described above for the various variables is contemplated herein. Throughout the specification, groups and substituents thereof are chosen by one skilled in the art to provide stable moieties and compounds.

[0032] Also described herein is a pharmaceutical composition comprising a compound as described herein, or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical composition is formulated for administration to a mammal by intravenous administration, subcutaneous administration, oral administration, inhalation, nasal administration, dermal administration, or ophthalmic administration. In some embodiments, the pharmaceutical composition is formulated for administration to a mammal by oral administration. In some embodiments, the pharmaceutical composition is in the form of a tablet, pill, capsule, liquid, suspension, gel, dispersion, solution, emulsion, ointment, or lotion. In some embodiments, the pharmaceutical composition is in the form of a tablet, pill, or capsule.

[0033] Also described herein is a method for treating a disease or condition in a mammal that would benefit from modulation of somatostatin receptor activity, the method comprising administering a compound as described herein or a pharmaceutically acceptable salt or solvate thereof to a mammal in need thereof. In some embodiments, the compound as described herein or a pharmaceutically acceptable salt or solvate thereof is administered orally. In some embodiments, the disease or condition is persistent or recurrent hyperinsulinemia, hypoglycemia, acromegaly, neuroendocrine tumors, insulinomas, Cushing's disease, ophthalmic diseases or conditions, cancer, pain, neurodegenerative diseases or conditions, inflammatory diseases or conditions, mental illnesses or conditions, or a combination thereof. In some embodiments, the disease or condition is hyperinsulinemic hypoglycemia. In some embodiments, the disease or condition is hypoglycemia due to endogenous insulin, drug-induced hyperinsulinemia, or hypoglycemia due to exogenous insulin.

[0034] Any of the above aspects is a further embodiment, wherein an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof is: (a) administered systemically to a mammal; and / or (b) administered orally to a mammal; and / or (c) administered intravenously to a mammal; and / or (d) administered by inhalation; and / or (e) administered by nasal administration; and / or (f) administered by injection to a mammal; and / or (g) administered topically to a mammal; and / or (h) administered by ocular administration; and / or (i) administered rectally to a mammal; and / or (j) administered non-systemically or topically to a mammal.

[0035] Any of the above aspects are further embodiments comprising a single administration of an effective amount of the compound, including further embodiments wherein the compound is administered to a mammal once daily or the compound is administered to a mammal multiple times over a one-day period. In some embodiments, the compound is administered according to a continuous dosing regimen. In some embodiments, the compound is administered according to a continuous daily dosing regimen.

[0036] In any of the embodiments disclosed herein, the mammal is a human.

[0037] In some embodiments, the compounds provided herein are administered orally to a human.

[0038] An article of manufacture is provided that includes packaging material, a compound of formula (I) or a pharmaceutically acceptable salt thereof within the packaging material, and a label indicating that the compound or composition, or a pharmaceutically acceptable salt, tautomer, pharmaceutically acceptable N-oxide, pharmaceutically active metabolite, pharmaceutically acceptable prodrug, or pharmaceutically acceptable solvate thereof, is used to modulate one or more subtypes of somatostatin receptor proteins, or to treat, prevent, or ameliorate one or more symptoms of a disease or condition that would benefit from modulation of one or more subtypes of somatostatin receptor proteins.

[0039] Other objects, features and advantages of the compounds, methods and compositions described herein will become apparent from the following detailed description. However, it should be understood that the detailed description and specific examples, while indicating specific embodiments, are given by way of illustration only, as various changes and modifications within the spirit and scope of the present disclosure will become apparent to those skilled in the art from this detailed description. DETAILED DESCRIPTION

[0040] Somatostatin (SST), also known as somatostatin release inhibitory factor (SRIF), was originally isolated from the sheep hypothalamus as a 14 amino acid peptide (Brazeau et al., Science 179, 77-79, 1973). Subsequently, a 28 amino acid peptide with an N-terminal extension was isolated, which has similar biological activity to the 14 amino acid somatostatin (Pradayrol et al., FEBS Letters, 109, 55-58, 1980; Esch et al., Proc. Natl. Acad. Sci. USA, 77, 6827–6831, 1980). SST is a regulatory peptide produced by several cell types in response to other neuropeptides, neurotransmitters, hormones, cytokines and growth factors. SST acts through endocrine and paracrine pathways to affect its target cells. Many of these effects are related to the inhibition of the secretion of other hormones, the most notable being growth hormone (GH). They are produced by various cell types in the central nervous system (CNS) and intestine and have multiple functions, including regulating the secretion of growth hormone (GH), insulin, glucagon, and many other antiproliferative hormones.

[0041] These pleiotropic effects of somatostatin are mediated by six somatostatin receptor proteins (SSTR1, SSTR2a, SSTR2b, SSTR3, SSTR4, SSTR5). These six somatostatin receptor proteins are encoded by five different somatostatin receptor genes (Reisine and Bell, Endocr Rev. 16, 427-442, 1995; Patel and Srikant, Trends Endocrinol Metab 8, 398-405, 1997). All of these receptors are members of the class A subgroup of the GPCR superfamily.

[0042] Any one or a combination of somatostatin receptor subtypes can be selectively modulated. In some embodiments, selectively modulating any one somatostatin receptor subtype relative to other somatostatin receptor subtypes reduces undesirable side effects in various clinical applications.

[0043] In one aspect, the compounds described herein are modulators of SSTR5. In some embodiments, the compounds described herein selectively modulate the activity of SSTR5 relative to other somatostatin receptors. In some embodiments, the compounds described herein selectively modulate the activity of SSTR5 relative to SSTR2.

[0044] In some embodiments, the compounds described herein are suitable for oral administration to a mammal in need of treatment with a somatostatin modulator.

[0045] In some embodiments, the somatostatin receptor modulators described herein are used for a wide range of therapeutic applications. In some embodiments, the somatostatin receptor modulators described herein are used to treat a variety of diseases or conditions, such as, but not limited to, acromegaly, neuroendocrine tumors, and hyperinsulinemia. In some embodiments, the somatostatin receptor modulators described herein are used to treat hyperinsulinemia in mammals.

[0046] In some embodiments, the somatostatin receptor modulators described herein inhibit the secretion of various hormones and nutritional factors in mammals. In some embodiments, the compounds are used to inhibit certain endocrine secretions, such as, but not limited to, GH, IGF-1, and insulin. The inhibition of certain endocrine secretions can be used to treat conditions such as acromegaly, hyperinsulinemia, endocrine tumors such as carcinoids, VIPomas, insulinomas, and glucagonomas. In some embodiments, the somatostatin receptor modulators described herein are used to inhibit exocrine secretions in the pancreas, stomach, and intestines for the treatment of conditions associated with diseases such as AIDS or cholera, such as pancreatitis, fistulas, bleeding ulcers, and diarrhea. Conditions involving the autocrine or paracrine secretion of trophic factors such as IGF-1 (as well as some endocrine factors) that may be treated by administration of the compounds described herein include breast, prostate, and lung cancer (small cell and non-small cell epidermoid carcinomas), as well as hepatoma, neuroblastoma, insulinoma, colon and pancreatic adenocarcinoma (ductal type), chondrosarcoma, and melanoma, as well as atherosclerosis associated with restenosis after vascular grafting and angioplasty.

[0047] In some embodiments, the somatostatin receptor modulators described herein are used to inhibit mediators of neurogenic inflammation (e.g., substance P or tachykinins) and are useful in treating rheumatoid arthritis; psoriasis; localized inflammation, such as that associated with sunburn, eczema, or other sources of itching; inflammatory bowel disease; irritable bowel syndrome; allergies, including asthma and other respiratory diseases. In some other embodiments, the somatostatin receptor modulators described herein act as neuromodulators in the central nervous system and are useful in treating Alzheimer's disease and other forms of dementia, pain, and headaches. In some embodiments, the somatostatin receptor modulators described herein provide cytoprotection in conditions involving splanchnic blood flow, including cirrhosis of the liver and esophageal varices.

[0048] In some embodiments, the somatostatin receptor modulators described herein are used to treat hyperinsulinemia in a mammal. Hyperinsulinemia can lead to several conditions, such as, but not limited to, hypoglycemia or low blood sugar, diabetes or uncontrolled blood sugar that fluctuates between high and low levels, increased risk of polycystic ovary syndrome (PCOS), increased production of very low-density lipoprotein (VLDL) (called hypertriglyceridemia), cardiovascular disease or heart disease, coronary artery disease (high insulin levels damage the endothelial cells lining the coronary arteries), hypertension or high blood pressure, hypothyroidism, weight gain, and increased risk of lethargy.

[0049] Hyperinsulinemia refers to higher-than-normal levels of insulin in a person or animal's blood. Normal insulin secretion and blood levels are closely related to blood glucose levels, so a given insulin level may be normal for one blood glucose level but low or high for another. Hyperinsulinemia can be associated with several types of medical problems, which can be roughly divided into two major, largely non-overlapping categories: those that tend to have decreased sensitivity to insulin and high blood glucose levels (hyperglycemia) and those that tend to have excessive insulin secretion and low glucose levels (hypoglycemia).

[0050] Hyperinsulinemic hypoglycemia (HH) is one of the most common causes of persistent hypoglycemia in infants. It is a heterogeneous condition caused by increased insulin secretion from the pancreatic beta cells. HH can lead to respiratory arrest, seizures, developmental delays, learning disabilities, epilepsy, and even death. The most severe form of HH is inherited and is called congenital hyperinsulinemia (CHI). As with many rare diseases, while there are currently no medications specifically for patients with CHI, some medications have been adapted for use, including but not limited to diazoxide and octreotide.

[0051] The pancreas is the primary site of somatostatin's action, where it inhibits the synthesis and secretion of two major hormones that control glucose homeostasis: glucagon and insulin. Different somatostatin receptor subtypes control these important processes: the SST2 receptor inhibits glucagon, while both SST2 and SST5 are responsible for inhibiting insulin.

[0052] Hypoglycemia due to excess endogenous insulin may be congenital or acquired, becoming apparent in the neonatal period or many years later. Hypoglycemia may be severe and life-threatening or mild and occasionally troublesome. By far, the most common type of severe but transient hyperinsulinemic hypoglycemia occurs incidentally in patients with type 1 diabetes taking insulin.

[0053] Hypoglycemia caused by endogenous insulin includes, but is not limited to, congenital hyperinsulinemia, transient neonatal hyperinsulinemia, focal hyperinsulinemia (KATP channel disorders), diffuse hyperinsulinemia, acquired forms of hyperinsulinemia, insulinoma (insulin-secreting tumor), adult islet cell hyperplasia, autoimmune insulin syndrome, non-insulinoma pancreatic hypoglycemia, reactive hypoglycemia, side effects of gastric bypass surgery, or gastric dumping syndrome.

[0054] Drug-induced hyperinsulinemia results from exposure to certain drugs such as, but not limited to, sulfonylureas, aspirin, pentamidine, quinine, disopyramide, Bordetella pertussis vaccine or infection, D-chiro-inositol, and myo-inositol.

[0055] Hypoglycemia results from exogenous (injected) insulin, including but not limited to self-injected insulin for the treatment of diabetes (i.e., diabetic hypoglycemia), surreptitious self-injection of insulin (e.g., Munchausen syndrome), self-injection of insulin during attempted or successful suicide, insulin potentiation therapy, and insulin-induced coma for the treatment of depression.

[0056] Compound

[0057] The compounds of formula (I), including their pharmaceutically acceptable salts, prodrugs, active metabolites and pharmaceutically acceptable solvates, are somatostatin receptor modulators. In some embodiments, the compounds of formula (I), including their pharmaceutically acceptable salts, prodrugs, active metabolites and pharmaceutically acceptable solvates, are SST5 receptor modulators.

[0058] In some embodiments, the compounds described herein are SST5 selective modulators. In some embodiments, the compounds described herein are at least 10-fold, at least 15-fold, at least 20-fold, at least 30-fold, at least 40-fold, at least 50-fold, at least 100-fold, at least 200-fold, at least 300-fold, at least 400-fold, or greater than 500-fold more selective for modulating SST5 receptor activity than for modulating SST1, SST2, SST3, and / or SST4 receptor activity. In some embodiments, the compounds described herein are at least 10-fold, at least 15-fold, at least 20-fold, at least 30-fold, at least 40-fold, at least 50-fold, at least 100-fold, at least 200-fold, at least 300-fold, at least 400-fold, or greater than 500-fold more selective for modulating SST5 receptor activity than for modulating SST2 receptor activity.

[0059] In one aspect, provided herein is a compound of formula (I), or a pharmaceutically acceptable salt, or a pharmaceutically acceptable solvate thereof:

[0060]

[0061] in:

[0062] Ring A is a carbocyclic ring or a heterocyclic ring;

[0063] X is N or C–R a ; Y is N or C–R b ; Z is N or C–R c ;

[0064] R a 、R b and R c are independently hydrogen, halogen, –CN, –N(R 9 )2. –OR f , –CO2R 9 、–C(=O)N(R 9 )2, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 fluoroalkoxy, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted monocyclic carbocycle, or substituted or unsubstituted monocyclic heterocycle;

[0065] R f -L 1 -R g ;

[0066] L 1 is absent, C1-C6 alkylene, C1-C6 fluoroalkylene, or C1-C6 heteroalkylene;

[0067] R g is hydrogen, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, -CO2R 9 、-C(=O)N(R 9 ) 2, or substituted or unsubstituted monocyclic heterocycle;

[0068] R 1 and R 2 are independently hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C6 cycloalkyl, or substituted or unsubstituted C3-C5 heterocycloalkyl;

[0069] R 3 For hydrogen, -CN, –CO2R 9 、–C(=O)N(R 9)2, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl;

[0070] R 4 and R 5 are independently hydrogen, halogen, –OR 9 ,–N(R 9 )2, –CN, –CO2R 9 、–C(=O)N(R 9 )2, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl;

[0071] R 6 is substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C1-C8 fluoroalkyl, substituted or unsubstituted C1-C8 heteroalkyl, or -L 2 -R 6a ;

[0072] L 2 is absent, substituted or unsubstituted C1-C8 alkylene, or -CHR 6b -;

[0073] R 6a is substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted C2-C 10 Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl;

[0074] R 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl;

[0075] R 7 is hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted C2-C 10 Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl;

[0076] or R 6 and R7 together with the nitrogen to which they are attached, form a substituted or unsubstituted N-containing heterocyclic ring;

[0077] Each R 8 、R 11 and R 12 are independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted monocyclic carbocycle, substituted or unsubstituted monocyclic heterocycle, -CN, -OR 9 、–C(=O)R 10 , –CO2R 9 、–C(=O)N(R 9 )2, –N(R 9 )2, –NR 9 C(=O)R 10 ,–NR 9 C(=O)OR 10 ,–NR 9 C(=O)N(R 9 )2, –C(R 9 )=N-OR 9 ,–SR 9 、–S(=O)R 9 ,–SO2R 9 , or –SO2N(R 9 )2;

[0078] or R 11 With adjacent R 8 And R 11 and adjacent R 8 The linked atoms together form a fused substituted or unsubstituted carbocyclic ring, or a fused substituted or unsubstituted heterocyclic ring;

[0079] Each R 9 are independently hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted monocyclic heteroaryl;

[0080] or two R on the same N atom 9 together with the nitrogen atom to which they are attached, form a substituted or unsubstituted N-containing heterocyclic ring;

[0081] Each R 10are independently substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted monocyclic heteroaryl; and

[0082] n is 0-3.

[0083] For any and all embodiments, the substituents are selected from a subset of the listed alternatives. For example, in some embodiments, R 1 and R 2 is independently hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl. 1 and R 2 is independently hydrogen or substituted or unsubstituted C1-C6 alkyl. 1 and R 2 are independently hydrogen or C1-C6 alkyl. 1 is hydrogen and R 2 is hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl. 1 is hydrogen and R 2 R is hydrogen or substituted or unsubstituted C1-C6 alkyl. 1 is hydrogen and R 2 is hydrogen or C1-C6 alkyl. 1 and R 2 Each is hydrogen.

[0084] In some embodiments, R 3 is hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl. 3 For hydrogen, -CN, –CO2R 9 、–C(=O)N(R 9 )2, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 fluoroalkyl or substituted or unsubstituted C1-C4 heteroalkyl. In some embodiments, R 3 is hydrogen, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 fluoroalkyl, or substituted or unsubstituted C1-C4 heteroalkyl.3 For hydrogen, -CN, –CO2R 9 、–C(=O)N(R 9 )2, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl. In some embodiments, R 3 is hydrogen, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl. 3 For hydrogen, -CN, –CO2R 9 、–C(=O)N(R 9 ) 2, or substituted or unsubstituted C1-C6 alkyl. In some embodiments, R 3 is hydrogen, or substituted or unsubstituted C1-C6 alkyl. 3 is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 alkoxy, C1-C6 fluoroalkoxy, or C1-C6 heteroalkyl. 3 For hydrogen, -CN, –CO2R 9 、–C(=O)N(R 9 )2, C1-C4 alkyl, C1-C4 fluoroalkyl or C1-C4 heteroalkyl. In some embodiments, R 3 is hydrogen, C1-C4 alkyl, C1-C4 fluoroalkyl or C1-C4 heteroalkyl. 3 For hydrogen, -CN, –CO2R 9 、–C(=O)N(R 9 )2, C1-C6 alkyl, or C1-C6 fluoroalkyl. In some embodiments, R 3 is hydrogen, C1-C6 alkyl, or C1-C6 fluoroalkyl. 3 is hydrogen or C1-C6 alkyl. 3 For hydrogen, -CN, –CO2R 9 、–C(=O)N(R 9 )2, or C1-C6 alkyl. In some embodiments, R 3 is hydrogen, -CN, -CO2CH3, -CO2CH2CH3, -C(=O)NH2, -C(=O)NHCH3, -C(=O)N(CH3)2, -CH3, -CH2OH, -CH2OCH3, -CH2CH2F, -CH2CHF2, or -CH2CF3. In some embodiments, R 3is hydrogen, -CN, -CO2CH3, -CO2CH2CH3, -C(=O)NH2, -C(=O)NHCH3, -C(=O)N(CH3)2, -CH3, -CH2OH, -CH2OCH3, or -CH2CHF2. In some embodiments, R 3 is hydrogen, -CH3, -CH2OH, -CH2OCH3, -CH2CH2F, -CH2CHF2, or -CH2CF3. In some embodiments, R 3 is hydrogen, -CH3, -CH2OH, -CH2OCH3, or -CH2CHF2. In some embodiments, R 3 is hydrogen or -CH3. In some embodiments, R 3 In some embodiments, R 3 is -CH3.

[0085] In some embodiments, R 4 and R 5 are independently hydrogen, halogen, –OR 9 ,–N(R 9 )2, –CN, –CO2R 9 、–C(=O)N(R 9 )2, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl. In some embodiments, R 4 and R 5 are each independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl. 4 and R 5 are each independently hydrogen, halogen, C1-C6 alkyl, or C1-C6 fluoroalkyl. 4 and R 5 Each is independently hydrogen or halogen. In some embodiments, R 4 and R 5 are each independently hydrogen or -F.

[0086] In some embodiments, R 1 is hydrogen; R 2 is hydrogen or C1-C6 alkyl; R 3 is hydrogen, C1-C6 alkyl, or C1-C6 fluoroalkyl; and R 4 and R 5 are each independently hydrogen, halogen, C1-C6 alkyl, or C1-C6 fluoroalkyl. 1 and R 2 Each is hydrogen; R 3 is hydrogen or -CH3; and R 4and R 5 In some embodiments, R 1 is hydrogen; R 2 is hydrogen or C1-C6 alkyl; R 3 is hydrogen, C1-C6 alkyl, or C1-C6 fluoroalkyl; R 4 is hydrogen, halogen, C1-C6 alkyl, or C1-C6 fluoroalkyl; and R 5 is hydrogen, halogen, C1-C6 alkyl, or C1-C6 fluoroalkyl. 1 is hydrogen; R 2 is hydrogen; R 3 is hydrogen, -CH3, -CH2OH, -CH2OCH3, -CH2CH2F, -CH2CHF2, or -CH2CF3; R 4 is hydrogen or F; and R 5 is hydrogen or F. In some embodiments, R 1 is hydrogen; R 2 is hydrogen or C1-C6 alkyl; R 3 is hydrogen, C1-C4 alkyl, C1-C4 fluoroalkyl or C1-C4 heteroalkyl; R 4 is hydrogen, halogen, C1-C4 alkyl, or C1-C4 fluoroalkyl; and R 5 is hydrogen, halogen, C1-C4 alkyl, or C1-C4 fluoroalkyl.

[0087] In some embodiments, the compound has the structure of Formula (Ia) or (Ib), or a pharmaceutically acceptable salt or solvate thereof:

[0088]

[0089] In some embodiments, the compound has the structure of Formula (Ia) or a pharmaceutically acceptable salt or solvate thereof:

[0090]

[0091] In some embodiments, the compound has the structure of Formula (Ib) or a pharmaceutically acceptable salt or solvate thereof:

[0092]

[0093] In some embodiments, X is C-R a ; Y is N; and Z is C–R c ; or X is CH; Y is N; and Z is C–R c ; or X is C–R a ; Y is N; and Z is CH; or X is N; Y is C–R b ; and Z is C–R c; or X is C–R a ; Y is C–R b ; and Z is N; or X is N; Y is N; and Z is C–R c ; or X is C–R a ; Y is N; and Z is N. In some embodiments, X is C—R a ; Y is N; and Z is C–R c In some embodiments, X is CH; Y is N; and Z is C-R c In some embodiments, X is C-R a ; Y is N; and Z is CH. In some embodiments, X is N; Y is C—R b ; and Z is C–R c In some embodiments, X is C-R a ; Y is C–R b ; and Z is N. In some embodiments, X is N; Y is N; and Z is C-R c In some embodiments, X is C-R a ; Y is N; and Z is N.

[0094] In some embodiments, X is N or CH; Y is N or CH; and Z is N or C-R c .

[0095] In some embodiments, R a 、R b and R c are independently hydrogen, halogen, –CN, –N(R 9 )2. –OR f , substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted monocyclic carbocycle, or substituted or unsubstituted monocyclic heterocycle. In some embodiments, R a 、R b and R c are independently hydrogen, halogen, –CN, –OR f , substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 fluoroalkoxy, or substituted or unsubstituted monocyclic carbocycle. In some embodiments, R a 、R b and R c are independently hydrogen, halogen, –CN, –OR f , C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, or a monocyclic carbocycle. a 、Rb and R c are independently hydrogen, halogen, –CN, –N(R 9 )2. –OR f , C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl. In some embodiments, R a 、R b and R c are independently hydrogen, halogen, –CN, –N(R 9 )2. –OR f , –CO2R 9 、–C(=O)N(R 9 ) 2、 C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, substituted or unsubstituted monocyclic C3-C6 cycloalkyl, or substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl.

[0096] In some embodiments, R a 、R b and R c are independently hydrogen, halogen, –CN, –N(R 9 )2. –OR f , –CO2R 9 、–C(=O)N(R 9 ) 2、 C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted monocyclic C3-C6 cycloalkyl, substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl; R f -L 1 -R g ;L 1 is absent, or C1-C6 alkylene; and R g is hydrogen, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, -CO2R 9 、-C(=O)N(R 9 ) 2. substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl. In some embodiments, R a 、R b and R c are independently hydrogen, halogen, –CN, –N(R 9 )2. –OR f , C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl; R f -L 1 -R g;L 1 is absent or C1-C6 alkylene; and R g is hydrogen, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, or -CO2R 9 .

[0097] In some embodiments, R a 、R b and R c Each is independently hydrogen, -F, -Cl, -CN, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH2CH2CH3, -CH2CH(CH3)2, -CH(CH3)(CH2CH3), -C(CH3)3, -CH2F, -CHF2, -CF3, -CH2CF3, -OCH3, -OCH2CH3, -OCF3, -OCH2CHF2, -OCH2CF3, -OCH2CH2OCH3, -O-(cyclopropyl), -O-CH2-(cyclopropyl), -O-CH2-(phenyl), -OCH In some embodiments, R a 、R b and R c Each is independently hydrogen, -F, -Cl, -CN, -CH3, -CF3, -OCH3, -OCH2CH3, -OCH2CHF2, -OCH2CF3, -OCH2CH2OCH3, -O-(cyclopropyl), -O-CH2-(cyclopropyl), -O-CH2-(phenyl), -OCH2CO2H, -OCH2CH2CO2H, -OCH2CH2CH2CO2H, -OCH2CO2CH3, -OCH2CH2CO2CH3, -OCH2CH2CO2CH3, -OCH2CH2CH2CO2CH3, -OCH2CO2CH2CH3, -OCH2CH2CO2CH2CH3, or -OCH2CH2CH2CO2CH2CH3. In some embodiments, R a 、R b and R care each independently hydrogen, -CN, -CH3, -CF3, -OCH3, -OCF3, -CO2CH3, -C(=O)NH2, -CONHCH3, or -C(=O)N(CH3)2. In some embodiments, R a 、R b and R c Each is independently hydrogen, -CN, -CH3, -CF3, -OCH3, -OCF3, -CO2CH3, -C(=O)NH2, -CONHCH3, or -C(=O)N(CH3)2, or cyclopropyl. In some embodiments, R a 、R b and R c are each independently hydrogen or -CN.

[0098] In some embodiments, the compound has the structure of Formula (II), or a pharmaceutically acceptable salt or solvate thereof:

[0099]

[0100] In some embodiments, the compound has the structure of Formula (IIa) or (IIb), or a pharmaceutically acceptable salt or solvate thereof:

[0101]

[0102] In some embodiments, the compound has the structure of Formula (IIa), or a pharmaceutically acceptable salt or solvate thereof:

[0103]

[0104] In some embodiments, the compound has the structure of Formula (IIb), or a pharmaceutically acceptable salt or solvate thereof:

[0105]

[0106] In some embodiments, the compound has the structure of Formula (IX), or a pharmaceutically acceptable salt or solvate thereof:

[0107]

[0108] In some embodiments, the compound has the structure of Formula (IIa) or (IIb), or a pharmaceutically acceptable salt or solvate thereof:

[0109]

[0110] In some embodiments, the compound has the structure of Formula (X), or a pharmaceutically acceptable salt or solvate thereof:

[0111]

[0112] In some embodiments, the compound has the structure of Formula (Xa) or (Xb), or a pharmaceutically acceptable salt or solvate thereof:

[0113]

[0114] In some embodiments, Ring A is phenyl, monocyclic heteroaryl, or bicyclic heteroaryl.

[0115] In some embodiments, Ring A is phenyl.

[0116] In some embodiments, Ring A is a monocyclic heteroaryl; and n is 0, 1, or 2. In some embodiments, Ring A is pyrrolyl, furanyl, thiophenyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, or triazinyl. In some embodiments, Ring A is pyrazolyl, thiazolyl, isoxazolyl, pyridinyl, or pyrimidinyl. In some embodiments, Ring A is pyridinyl.

[0117] In some embodiments, Ring A is phenyl or a monocyclic heteroaryl. In some embodiments, Ring A is phenyl; or Ring A is pyridinyl; or Ring A is pyrazolyl, thiazolyl, isoxazolyl, or pyrimidinyl. In some embodiments, Ring A is phenyl or pyridinyl.

[0118] In some embodiments, the compound has the structure of Formula (III), or a pharmaceutically acceptable salt or solvate thereof:

[0119]

[0120] In some embodiments, the compound has the structure of Formula (IIIa) or (IIIb), or a pharmaceutically acceptable salt or solvate thereof:

[0121]

[0122] In some embodiments, the compound has the structure of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof:

[0123]

[0124] in:

[0125] A 1 and A 2 Each independently is C–R 8 or N; and

[0126] A3 C–R 12 or N.

[0127] In some embodiments, the compound has the structure of Formula (IVa) or (IVb), or a pharmaceutically acceptable salt or solvate thereof:

[0128]

[0129] In some embodiments, A 1 C–R 8 ; A 2 C–R 8 , and A 3 C–R 12 ; or A 1 N; A 2 C–R 8 , and A 3 C–R 12 ; or A 1 C–R 8 ; A 2 is N, and A 3 C–R 12 ; or A 1 C–R 8 ; A 2 C–R 8 , and A 3 is N. In some embodiments, A 1 C–R 8 ; A 2 C–R 8 , and A 3 C–R 12 In some embodiments, A 1 N; A 2 C–R 8 , and A 3 C–R 12 In some embodiments, A 1 C–R 8 ; A 2 is N, and A 3 C–R 12 In some embodiments, A 1 C–R 8 ; A 2 C–R 8 , and A 3 is N.

[0130] In some embodiments, the compound has the structure of Formula (IVa-1) or (IVb-1), or a pharmaceutically acceptable salt or solvate thereof:

[0131]

[0132] in:

[0133] A 1 C–R 8 ; and A 2 C–R 8 ;or

[0134] A 1 is N; and A 2 C–R 8 ;or

[0135] A 1 C–R 8 ; and A 2 is N.

[0136] In some embodiments, the compound has the structure of Formula (IVa-2), (IVb-2), (IVa-3), (IVb-3), (IVa-4), (IVb-4), (IVa-5), or (IVb-5), or a pharmaceutically acceptable salt or solvate thereof:

[0137]

[0138] In some embodiments, the compound has the structure of Formula (V), or a pharmaceutically acceptable salt or solvate thereof:

[0139]

[0140] in:

[0141] A 2 C–R 8 or N.

[0142] In some embodiments, the compound has the structure of Formula (Va) or (Vb), or a pharmaceutically acceptable salt or solvate thereof:

[0143]

[0144] In some embodiments, the compound has the structure of Formula (Va-1), (Vb-1), (Va-2), or (Vb-2), or a pharmaceutically acceptable salt or solvate thereof:

[0145]

[0146] In some embodiments, each R 8are independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted monocyclic carbocycle, -CN, -OR 9 , –CO2R 9 、–C(=O)N(R 9 )2, –N(R 9 )2, –NR 9 C(=O)R 10 ,–SO2R 9 , or –SO2N(R 9 )2. In some embodiments, each R 8 are independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, -CN, -OR 9 , –CO2R 9 、–C(=O)N(R 9 )2, –N(R 9 )2, or –NR 9 C(=O)R 10 In some embodiments, each R 8 R is independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl. 8 is independently hydrogen, halogen, C1-C6 alkyl, or C1-C6 fluoroalkyl. 8 is independently hydrogen or halogen. In some embodiments, each R 8 are independently hydrogen, -F or -Cl.

[0147] In some embodiments, the compound has the structure of Formula (Va-3) or (Vb-3), or a pharmaceutically acceptable salt or solvate thereof:

[0148]

[0149] In some embodiments, R 11 and R 12 Each is independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted monocyclic carbocycle, substituted or unsubstituted monocyclic heterocycle, -CN, -OR 9 , –CO2R 9 、–C(=O)N(R 9 )2, –N(R 9 )2, –NR 9 C(=O)R 10 ,–NR 9C(=O)OR 10 ,–NR 9 C(=O)N(R 9 )2, –C(R 9 )=N-OR 9 ,–SR 9 、–S(=O)R 9 ,–SO2R 9 or –SO2N(R 9 )2. In some embodiments, R 11 and R 12 Each is independently hydrogen, halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, -CN, -OR 9 , –CO2R 9 、–C(=O)N(R 9 )2, –N(R 9 )2, or –NR 9 C(=O)R 10 , substituted or unsubstituted monocyclic C3-C8 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl, or substituted or unsubstituted monocyclic C1-C5 heteroaryl. In some embodiments, R 11 and R 12 are each independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, -CN, -OR 9 , –CO2R 9 、–C(=O)N(R 9 )2, –N(R 9 )2, or –NR 9 C(=O)R 10 , or a substituted or unsubstituted monocyclic carbocyclic ring. In some embodiments, R 11 and R 12 are each independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, -CN, -OR 9 , –CO2R 9 、–C(=O)N(R 9 )2, –N(R 9 )2, or –NR 9 C(=O)R 10 , or substituted or unsubstituted monocyclic C3-C8 cycloalkyl. In some embodiments, R 11 and R 12 are each independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, -CN, -OR 9, or substituted or unsubstituted monocyclic cycloalkyl. In some embodiments, R 11 and R 12 are each independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, -CN, -OR 9 , or substituted or unsubstituted monocyclic C3-C8 cycloalkyl. In some embodiments, R 11 and R 12 Each is independently hydrogen, halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, -CN, -OR 9 , or substituted or unsubstituted monocyclic C3-C8 cycloalkyl. In some embodiments, R 11 and R 12 are each independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, -CN, -OR 9 In some embodiments, R 11 and R 12 Each is independently hydrogen, halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, -CN, or -OR 9 In some embodiments, R 11 and R 12 are each independently hydrogen, -F, -Cl, -CN, -CH3, -CF3, -OCH3, -OCF3, or -OCHF2. In some embodiments, R 11 and R 12 are each independently halogen. In some embodiments, R 11 and R 12 Each is independently -F or -Cl. In some embodiments, R 11 and R 12 Each is -F.

[0150] In some embodiments, R 11 With adjacent R 8 And R 11 and adjacent R 8 The atoms joined together form a fused substituted or unsubstituted carbocyclic ring, or a fused substituted or unsubstituted heterocyclic ring. 11 With adjacent R 8 And R 11 and adjacent R 8 The atoms connected together form a fused substituted or unsubstituted C3-C8 cycloalkyl, or a fused substituted or unsubstituted C2-C5 heterocycloalkyl. 11 With adjacent R 8 And R 11 and adjacent R8 The atoms connected together form a fused substituted or unsubstituted C2-C5 heterocycloalkyl. 11 With adjacent R 8 And R 11 and adjacent R 8 The linked atoms are taken together to form a fused substituted or unsubstituted dioxolane or a fused substituted or unsubstituted dioxane.

[0151] In some embodiments, each R 8 are independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, -CN, -OR 9 , –CO2R 9 、–C(=O)N(R 9 )2, –N(R 9 )2, or –NR 9 C(=O)R 10 ; and R 11 and R 12 Each is independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted monocyclic carbocycle, substituted or unsubstituted monocyclic heterocycle, -CN, -OR 9 , –CO2R 9 、–C(=O)N(R 9 )2, –N(R 9 )2, –NR 9 C(=O)R 10 ,–NR 9 C(=O)OR 10 ,–NR 9 C(=O)N(R 9 )2, –C(R 9 )=N-OR 9 ,–SR 9 、–S(=O)R 9 ,–SO2R 9 , or –SO2N(R 9 )2. In some embodiments, each R 8 are independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl; and R 11 and R 12 are each independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, -CN, -OR 9 , –CO2R 9 、–C(=O)N(R9 )2, –N(R 9 )2, or –NR 9 C(=O)R 10 , or a substituted or unsubstituted monocyclic carbocyclic ring. In some embodiments, each R 8 are independently hydrogen or halogen; and R 11 and R 12 are each independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, -CN, -OR 9 , or substituted or unsubstituted monocyclic cycloalkyl. In some embodiments, each R 8 are independently hydrogen or halogen; and R 11 and R 12 are each independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, -CN, -OR 9 , or substituted or unsubstituted monocyclic cycloalkyl. In some embodiments, each R 8 are independently hydrogen, -F or -Cl; and R 11 and R 12 Each is independently hydrogen, -F, -Cl, -CN, -CH3, -CF3, -OCH3, -OCF3 or -OCHF2.

[0152] In some embodiments, the compound has the structure of Formula (VI), or a pharmaceutically acceptable salt or solvate thereof:

[0153]

[0154] In some embodiments, R 3 is hydrogen or -CH3; R 8 is hydrogen or halogen; R 11 and R 12 are each independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, -CN, -OR 9 ; R c For hydrogen, halogen, –CN, –N(R 9 )2. –OR f , –CO2R 9 、–C(=O)N(R 9 )2, C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted monocyclic C3-C6 cycloalkyl, or substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl; R f -L 1 -R g ;L1 is absent or C1-C6 alkylene; and R g is hydrogen, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, -CO2R 9 、-C(=O)N(R 9 )2. Substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl.

[0155] In some embodiments, the compound has the structure of Formula (VIa) or (VIb), or a pharmaceutically acceptable salt or solvate thereof:

[0156]

[0157] In some embodiments, R 3 is hydrogen or -CH3; R 8 is hydrogen or halogen; R 11 and R 12 are each independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, -CN, -OR 9 ; R c For hydrogen, halogen, –CN, –N(R 9 )2. –OR f , –CO2R 9 、–C(=O)N(R 9 )2, C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted monocyclic C3-C6 cycloalkyl, or substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl; R f -L 1 -R g ;L 1 is absent or C1-C6 alkylene; and R g is hydrogen, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, -CO2R 9 、-C(=O)N(R 9 ) 2. substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl. In some embodiments, R c For hydrogen, halogen, –CN, –N(R 9 )2. –OR f , C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl; R f -L 1 -R g ;L 1 is absent or C1-C6 alkylene; and R gis hydrogen, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, or -CO2R 9 .

[0158] In some embodiments, R 8 is hydrogen, -F or -Cl; R 11 and R 12 are each independently hydrogen, -F, -Cl, -CN, -CH3, -CF3, -OCH3, -OCF3 or -OCHF2; and R c For hydrogen, -F, -Cl, -CN, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH2CH2CH3, -CH2CH(CH3)2, -CH(CH3)(CH2CH3), -C(CH3)3, -CH2F, -CHF2, -CF3, -CH2CF3, -OCH3, -OCH2CH3, -OCF3, -OCH2CHF2, -OCH2CF3, -OCH2CH2OCH3, -O-(cyclopropyl), -O-CH2-(cyclopropyl), -O-CH2-(phenyl), -OCH2C O2H, -OCH2CH2CO2H, -OCH2CH2CH2CO2H, -OCH2CO2CH3, -OCH2CH2CO2CH3, -OCH2CH2CH2CO2CH3, -OCH2CO2CH2CH3, -OCH2CH2CO2CH2CH3, -OCH2CH2CO2CH2CH3, -OCH2CH2CH2CO2CH2CH3, -CO2CH3, -CO2CH2CH3, -C(=O)NH2, -CONHCH3, -C(=O)N(CH3)2, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, pyrrolidinyl, piperidinyl or morpholinyl. In some embodiments, R c R is hydrogen, -F, -Cl, -CN, -CH, -CF, -OCH, -OCHCH, -OCHCHF, -OCHCF, -OCHCHOCH, -O-(cyclopropyl), -O-CH-(cyclopropyl), -O-CH-(phenyl), -OCHCOH, -OCHCHCOH, -OCHCHCHCOH, -OCHCOCH, -OCHCHCOCH, -OCHCHCOCH, -OCHCHCOCH, -OCHCHCOCHCH, -OCHCOCHCH, -OCHCOCHCH, -OCHCOCHCH, -OCHCOCHCH, or -OCHCHCHCOCHCH. In some embodiments, R cis hydrogen, -CN, -CH3, -CF3, -OCH3, -OCF3, -CO2CH3, -C(=O)NH2, -CONHCH3, or -C(=O)N(CH3)2, or cyclopropyl. In some embodiments, R c It is hydrogen, -CN, -CH3, -CF3, -OCH3, -OCF3, -CO2CH3, -C(=O)NH2, -CONHCH3, or -C(=O)N(CH3)2.

[0159] In some embodiments, the compound has the structure of Formula (VIa-1) or (VIb-1), or a pharmaceutically acceptable salt or solvate thereof:

[0160]

[0161] In some embodiments, R 3 is hydrogen or -CH3; and R c is hydrogen, -CN, -CH3, -CF3, -OCH3, -OCF3, -CO2CH3, -C(=O)NH2, -CONHCH3, or -C(=O)N(CH3)2. In some embodiments, R 11 and R 12 Each is independently hydrogen, halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, -CN, or -OR 9 In some embodiments, R 11 and R 12 are each independently hydrogen, -F, -Cl, -CN, -CH3, -CF3, -OCH3, -OCF3, or -OCHF2. In some embodiments, R 11 and R 12 are each independently halogen. In some embodiments, R 11 and R 12 Each is independently -F or -Cl. In some embodiments, R 11 and R 12 Each is -F.

[0162] In some embodiments, Ring A is a bicyclic heteroaryl. In some embodiments, Ring A is a 9-membered or 10-membered bicyclic heteroaryl. In some embodiments, Ring A is an indolyl, isoindolyl, indazolyl, benzimidazolyl, azaindolyl, benzisoxazolyl, benzoxazolyl, benzoisoxazolyl, benzothiazolyl, benzoxadiazolyl, benzothiadiazolyl, quinolinyl, isoquinolinyl, quinoxalinyl, or quinazolinyl. In some embodiments, Ring A is a benzimidazolyl, indazolyl, or benzoxadiazolyl. In some embodiments, Ring A is a benzimidazolyl.

[0163] In some embodiments, the compound has the structure of Formula (VII), or a pharmaceutically acceptable salt or solvate thereof:

[0164]

[0165] in:

[0166] R 8 is hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl.

[0167] In some embodiments, the compound has the structure of Formula (VIIa) or (VIIb), or a pharmaceutically acceptable salt or solvate thereof:

[0168]

[0169] In some embodiments, R c For hydrogen, halogen, –CN, –N(R 9 )2. –OR f , C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl; R f -L 1 -R g ;L 1 is absent or C1-C6 alkylene; and R g is hydrogen, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, or -CO2R 9 In some embodiments, R 8 is hydrogen, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH2CH2CH3, -CH2CH(CH3)2, -CH(CH3)(CH2CH3), or -C(CH3)3; and R cFor hydrogen, -F, -Cl, -CN, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH2CH2CH3, -CH2CH(CH3)2, -CH(CH3)(CH2CH3), -C(CH3)3, -CH2F, -CHF2, -CF3, -CH2CF3, -OCH3, -OCH2CH3, -OCF3, -OCH2CHF2, -OCH2CF3, -OCH2CH2OCH3, -O-(cyclopropyl), -O-CH2-(cyclopropyl), -O-CH2-(phenyl), -OCH2C O2H, -OCH2CH2CO2H, -OCH2CH2CH2CO2H, -OCH2CO2CH3, -OCH2CH2CO2CH3, -OCH2CH2CH2CO2CH3, -OCH2CO2CH2CH3, -OCH2CH2CO2CH2CH3, -OCH2CH2CO2CH2CH3, -OCH2CH2CH2CO2CH2CH3, -CO2CH3, -CO2CH2CH3, -C(=O)NH2, -CONHCH3, -C(=O)N(CH3)2, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, pyrrolidinyl, piperidinyl or morpholinyl. In some embodiments, R 8 is hydrogen, -CH3, -CH2CH3; and R c R is hydrogen, -F, -Cl, -CN, -CH, -CF, -OCH, -OCHCH, -OCHCHF, -OCHCF, -OCHCHOCH, -O-(cyclopropyl), -O-CH-(cyclopropyl), -O-CH-(phenyl), -OCHCOH, -OCHCHCOH, -OCHCHCHCOH, -OCHCOCH, -OCHCHCOCH, -OCHCHCOCH, -OCHCHCOCH, -OCHCHCOCHCH, -OCHCOCHCH, -OCHCOCHCH, -OCHCOCHCH, -OCHCOCHCH, or -OCHCHCHCOCHCH. In some embodiments, R c is hydrogen, -CN, -CH3, -CF3, -OCH3, -OCF3, -CO2CH3, -C(=O)NH2, -CONHCH3, or -C(=O)N(CH3)2, or cyclopropyl. In some embodiments, R c It is hydrogen, -CN, -CH3, -CF3, -OCH3, -OCF3, -CO2CH3, -C(=O)NH2, -CONHCH3, or -C(=O)N(CH3)2.

[0170] In some embodiments, n is 0, 1, 2, or 3. In some embodiments, n is 0, 1, or 2. In some embodiments, n is 1, 2, or 3. In some embodiments, n is 2 or 3. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3.

[0171] In some embodiments, for or Among them A 1 and A 2 Each independently is C–R 8 or N; and A 3 C–R 12 Or N. In some embodiments, for Among them A 2 C–R 8 Or N. In some embodiments, for In some embodiments, for In some embodiments, for In some embodiments, for In some embodiments, for In some embodiments, for where R 8 is hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl.

[0172] In some embodiments, R 7 is hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C3-C4 cycloalkyl, or substituted or unsubstituted C2-C3 heterocycloalkyl. 7 is hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C3-C4 cycloalkyl, or substituted or unsubstituted 3-membered or 4-membered heterocycloalkyl. 7 is hydrogen, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl. 7 is hydrogen or C1-C6 alkyl. 7is hydrogen or -CH3. In some embodiments, R 7 In some embodiments, R 7 is -CH3.

[0173] In some embodiments, R 6 is substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C1-C8 fluoroalkyl, substituted or unsubstituted C1-C8 heteroalkyl, or -L 2 -R 6a ;L 2 is absent, substituted or unsubstituted C1-C8 alkylene, or -CHR 6b -;R 6a is substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted C2-C 10 Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl; R 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl.

[0174] In some embodiments, R 6 is a substituted or unsubstituted C1-C8 alkyl, a substituted or unsubstituted C1-C8 fluoroalkyl, or a substituted or unsubstituted C1-C8 heteroalkyl. 6 is C1-C8 alkyl, C1-C8 fluoroalkyl, or substituted or unsubstituted C1-C8 heteroalkyl. 6 is C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C1-C6 heteroalkyl. 6 is C1-C6 alkyl, C1-C6 fluoroalkyl, or C1-C6 heteroalkyl. 6 is a substituted or unsubstituted C1-C8 alkyl group, or a substituted or unsubstituted C1-C8 fluoroalkyl group. 6 is a substituted or unsubstituted C1-C6 alkyl group, or a substituted or unsubstituted C1-C6 fluoroalkyl group. 6 is C1-C6 alkyl or C1-C6 fluoroalkyl. 6 In some embodiments, R 6 is C1-C6 fluoroalkyl. 6is -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH2CH2CH3, -CH2CH(CH3)2, -CH(CH3)(CH2CH3), -CH(CH2CH3)(CH2CH3), -CH(CH2CH2CH3)(CH2CH3), -C(CH3)(CHCH3)2, -C(CH3)3, -CH2F, -CHF2, -CF3, -CH2CF3, -CH(CF3)(CH3), -CH(CF3)(CH2CH3), -CH2CF2CH3, or -CH(CH3)(CH2CF3). In some embodiments, R 6 is -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH(CH3)2, -CH(CH3)(CH2CH3), -CH(CH2CH3)(CH2CH3), -CH2CF3, -CH(CF3)(CH3), or -CH(CF3)(CH2CH3).

[0175] In some embodiments, R 6 -L 2 -R 6a .

[0176] In some embodiments, L 2 is absent, substituted or unsubstituted C1-C8 alkylene, or -CHR 6b -. In some embodiments, L 2 is absent, substituted or unsubstituted C1-C6 alkylene, or -CHR 6b -. In some embodiments, L 2 is absent, C1-C6 alkylene, or -CHR 6b -. In some embodiments, L 2 is absent, C1-C4 alkylene, or -CHR 6b -. In some embodiments, L 2 is absent, -CH2-, -CH2CH2-, -CH2CH2CH2-, or -CHR 6b -. In some embodiments, L 2 is -CH2-, -CH2CH2-, -CH2CH2CH2-, or -CHR 6b -. In some embodiments, L 2 -CH2- or -CHR 6b -. In some embodiments, L 2 It is -CH2-, -CH(CH3)- or -CH(CF3)-.

[0177] In some embodiments, R 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl. 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C4 cycloalkyl. 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or C3-C4 cycloalkyl. 6b is hydrogen, C1-C4 alkyl, C1-C4 fluoroalkyl, or C3-C4 cycloalkyl. 6b is hydrogen, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CHF2, -CH2F, -CF3, cyclopropyl or cyclobutyl. In some embodiments, R 6b is hydrogen, -CH3, -CHF2, -CF3, cyclopropyl or cyclobutyl. In some embodiments, R 6b is hydrogen, -CH3, -CF3, or cyclopropyl. 6b is hydrogen, -CH3, or -CF3.

[0178] In some embodiments, R 6a is a substituted or unsubstituted monocyclic C3-C8 cycloalkyl, a substituted or unsubstituted polycyclic C5-C 10 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted indanyl, substituted or unsubstituted tetrahydronaphthyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl, substituted or unsubstituted polycyclic C5-C 10 In some embodiments, R 6a is a substituted or unsubstituted monocyclic C3-C6 cycloalkyl, a substituted or unsubstituted bridged C5-C 10 Cycloalkyl, substituted or unsubstituted spiro C5-C 10 In some embodiments, R 6a is a substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl, a substituted or unsubstituted bridged C5-C 10 Heterocycloalkyl, substituted or unsubstituted spiro C5-C 10 heterocycloalkyl, substituted or unsubstituted monocyclic C1-C5 heteroaryl, or substituted or unsubstituted bicyclic C6-C9 heteroaryl.

[0179] In some embodiments, R 6a is a substituted or unsubstituted monocyclic C3-C4 cycloalkyl, a substituted or unsubstituted monocyclic or bicyclic C5-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted monocyclic C2-C3 heterocycloalkyl, substituted or unsubstituted monocyclic or bicyclic C4-C 10 In some embodiments, R 6a is a substituted or unsubstituted monocyclic 3-membered or 4-membered monocyclic cycloalkyl, a 3-membered or 4-membered monocyclic heterocycloalkyl, a substituted or unsubstituted monocyclic or bicyclic C5-C 10 cycloalkyl, or substituted or unsubstituted 5- to 10-membered heteroaryl.

[0180] In some embodiments, R 6a is a substituted or unsubstituted C3-C4 cycloalkyl, or a substituted or unsubstituted 3-membered or 4-membered C2-C3 heterocycloalkyl. 6a In some embodiments, R 6a is a substituted or unsubstituted C3-C4 cycloalkyl. 6a is substituted or unsubstituted cyclopropyl, or substituted or unsubstituted cyclobutyl. 6a is a substituted or unsubstituted cyclopropyl. In some embodiments, R 6a is a substituted or unsubstituted cyclobutyl group.

[0181] In some embodiments, L 2 is absent, substituted or unsubstituted C1-C8 alkylene, or -CHR 6b -;R 6a is substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted C2-C 10 heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl; and R 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl. 2 is absent, C1-C6 alkylene, or -CHR 6b -;R 6ais a substituted or unsubstituted monocyclic C3-C8 cycloalkyl, a substituted or unsubstituted polycyclic C5-C 10 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted indanyl, substituted or unsubstituted tetrahydronaphthyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl, substituted or unsubstituted polycyclic C5-C 10 heterocycloalkyl, substituted or unsubstituted monocyclic C1-C5 heteroaryl, or substituted or unsubstituted bicyclic C6-C9 heteroaryl; and R 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl.

[0182] In some embodiments, L 2 is absent, C1-C4 alkylene, or -CHR 6b -; and R 6b is hydrogen, C1-C4 alkyl, C1-C4 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl. 6a is a substituted or unsubstituted monocyclic C3-C6 cycloalkyl, a substituted or unsubstituted bridged C5-C 10 Cycloalkyl, substituted or unsubstituted spiro C5-C 10 In some embodiments, R 6a is a substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl, a substituted or unsubstituted bridged C5-C 10 Heterocycloalkyl, substituted or unsubstituted spiro C5-C 10 heterocycloalkyl, substituted or unsubstituted monocyclic C1-C5 heteroaryl, or substituted or unsubstituted bicyclic C6-C9 heteroaryl.

[0183] In some embodiments, R 6a is a substituted or unsubstituted C3-C4 cycloalkyl group, or a substituted or unsubstituted 3-membered or 4-membered C2-C3 heterocycloalkyl group; and R 6b L is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C4 cycloalkyl. 2 is absent, -CH2-, -CH2CH2-, -CH2CH2CH2-, or -CHR 6b -;R 6a is substituted or unsubstituted cyclopropyl, substituted or unsubstituted cyclobutyl, substituted or unsubstituted azetidinyl, or substituted or unsubstituted oxetanyl; and R 6bIt is hydrogen, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CHF2, -CH2F, -CF3, cyclopropyl or cyclobutyl.

[0184] In some embodiments, R 6 and R 7 Together with the nitrogen to which they are attached, they form a substituted or unsubstituted N-containing heterocyclic ring. In some embodiments, R 6 and R 7 Together with the nitrogen to which they are attached, they form a substituted or unsubstituted N-containing heterocyclic ring that is monocyclic, bicyclic, or polycyclic. 6 and R 7 Together with the nitrogen to which they are attached, they form a substituted or unsubstituted N-containing heterocycloalkyl. In some embodiments, R 6 and R 7 Together with the nitrogen to which they are attached, they form a substituted or unsubstituted monocyclic N-containing heterocycloalkyl, or a substituted or unsubstituted polycyclic N-containing heterocycloalkyl. 6 and R 7 Together with the nitrogen to which they are attached, they form a substituted or unsubstituted monocyclic N-containing heterocycloalkyl group containing 1-2 N atoms, 0-2 O atoms, and 0-1 S. In some embodiments, R 6 and R 7 Together with the nitrogen to which they are attached, they form a substituted or unsubstituted bicyclic N-containing C5-C 10 Heterocycloalkyl, wherein the bicyclic N-containing C5-C 10 Heterocycloalkyl is a fused bicyclic C5-C 10 Heterocycloalkyl, bridged bicyclic C5-C 10 Heterocycloalkyl, or spirobicyclic C5-C 10 Heterocycloalkyl.

[0185] In certain embodiments,

[0186] R 7 is hydrogen, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl; and

[0187] R 6 is substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C1-C8 fluoroalkyl, substituted or unsubstituted C1-C8 heteroalkyl, or -L 2 -R 6a ;

[0188] L 2 is absent, substituted or unsubstituted C1-C8 alkylene, or -CHR 6b -;

[0189] R 6a is substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted C2-C 10 Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl;

[0190] R 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl;

[0191] or R 6 and R 7 Together with the nitrogen to which they are attached they form a substituted or unsubstituted N-containing heterocycloalkyl.

[0192] In some embodiments,

[0193] X is N or CH;

[0194] Y is N or CH;

[0195] Z is N or C–R c ;

[0196] R c For hydrogen, halogen, –CN, –N(R 9 )2. –OR f , C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl;

[0197] R f -L 1 -R g ;

[0198] L 1 is absent, C1-C6 alkylene, or C1-C6 fluoroalkylene;

[0199] R g is hydrogen, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, -CO2R 9 , or -C(=O)N(R 9 )2;

[0200] R 1 is hydrogen;

[0201] R 2 is H or C1-C6 alkyl;

[0202] R 3 is hydrogen, C1-C6 alkyl or C1-C6 fluoroalkyl;

[0203] R 4 is hydrogen, halogen, C1-C6 alkyl or C1-C6 fluoroalkyl;

[0204] R 5 is hydrogen, halogen, C1-C6 alkyl or C1-C6 fluoroalkyl;

[0205] R 6 is C1-C8 alkyl, C1-C8 fluoroalkyl, or -L 2 -R 6a ;

[0206] L 2 is absent, C1-C6 alkylene, or -CHR 6b -;

[0207] R 6a is substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted C2-C 10 Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl;

[0208] R 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl;

[0209] R 7 is H or C1-C6 alkyl;

[0210] or R 6 and R 7 Together with the nitrogen to which they are attached they form a substituted or unsubstituted heterocyclic ring.

[0211] In some embodiments, X is N or CH;

[0212] Y is N or CH;

[0213] Z is N or C–R c ;

[0214] R c is hydrogen, -CN, -CH3, -CF3, -OCH3, -OCF3, -CO2CH3, -C(=O)NH2, -CONHCH3, or -C(=O)N(CH3)2;

[0215] R 1 is hydrogen;

[0216] R 2 is hydrogen;

[0217] R 3is hydrogen, -CH3, -CH2OH, -CH2OCH3, -CH2CH2F, -CH2CHF2, or -CH2CF3;

[0218] R 4 is hydrogen or F;

[0219] R 5 is hydrogen or F;

[0220] R 6 is C1-C6 alkyl, C1-C6 fluoroalkyl, or -L 2 -R 6a ;

[0221] L 2 is absent, C1-C6 alkylene or -CHR 6b -;

[0222] R 6a is a substituted or unsubstituted monocyclic C3-C4 cycloalkyl, a substituted or unsubstituted monocyclic or bicyclic C5-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted monocyclic C2-C3 heterocycloalkyl, substituted or unsubstituted monocyclic or bicyclic C4-C 10 Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl;

[0223] R 6b is hydrogen, C1-C4 alkyl, C1-C4 fluoroalkyl, or substituted or unsubstituted monocyclic C3-C4 cycloalkyl;

[0224] R 7 is H or C1-C6 alkyl;

[0225] or R 6 and R 7 Together with the nitrogen to which they are attached they form a substituted or unsubstituted heterocyclic ring.

[0226] In some embodiments, the compound has the structure of Formula (VIII) or a pharmaceutically acceptable salt or solvate thereof:

[0227]

[0228] in:

[0229] Ring A is phenyl or pyridyl;

[0230] R a and R c are independently hydrogen, halogen, –CN, –N(R 9 )2. –OR f , –CO2R9 、–C(=O)N(R 9 )2, C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, substituted or unsubstituted monocyclic C3-C6 cycloalkyl, or substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl;

[0231] R f -L 1 -R g ;

[0232] L 1 is absent, or C1-C6 alkylene;

[0233] R g is hydrogen, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, -CO2R 9 , or -C(=O)N(R 9 )2, or substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl;

[0234] R 1 is hydrogen;

[0235] R 2 is H or C1-C6 alkyl;

[0236] R 3 is hydrogen, C1-C4 alkyl, C1-C4 fluoroalkyl or C1-C4 heteroalkyl;

[0237] R 4 is hydrogen, halogen, C1-C4 alkyl or C1-C4 fluoroalkyl;

[0238] R 5 is hydrogen, halogen, C1-C4 alkyl or C1-C4 fluoroalkyl;

[0239] R 6 is C1-C6 alkyl, C1-C6 fluoroalkyl, or -L 2 -R 6a ;

[0240] L 2 is absent, C1-C6 alkylene or -CHR 6b -;

[0241] R 6a is a substituted or unsubstituted monocyclic C3-C4 cycloalkyl, a substituted or unsubstituted monocyclic or bicyclic C5-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted monocyclic C2-C3 heterocycloalkyl, substituted or unsubstituted monocyclic or bicyclic C4-C 10Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl;

[0242] R 6b is hydrogen, C1-C4 alkyl, C1-C4 fluoroalkyl, or substituted or unsubstituted monocyclic C3-C4 cycloalkyl;

[0243] R 7 is H or C1-C6 alkyl;

[0244] Each R 8 are independently hydrogen, halogen, C1-C6 alkyl, or C1-C6 fluoroalkyl;

[0245] R 11 and R 12 Each is independently hydrogen, halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, -CN, -OR 9 , –CO2R 9 、–C(=O)N(R 9 )2、–N(R 9 )2, or –NR 9 C(=O)R 10 , or substituted or unsubstituted monocyclic C3-C8 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl, or substituted or unsubstituted monocyclic C1-C5 heteroaryl;

[0246] Each R 9 are independently hydrogen, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl;

[0247] or two R on the same N atom 9 together with the nitrogen atom to which they are attached, form a substituted or unsubstituted nitrogen-containing heterocyclic ring;

[0248] Each R 10 are independently substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl; and

[0249] n is 0-3.

[0250] In some embodiments, the compound has the structure of Formula (VIIIa) or (VIIIb) or a pharmaceutically acceptable salt or solvate thereof:

[0251]

[0252] In some embodiments, the compound has the structure of Formula (VIIIa-1) or (VIIIb-1) or a pharmaceutically acceptable salt or solvate thereof:

[0253]

[0254] In some embodiments, R 3 is hydrogen or -CH3; R 4 and R 5 Each is hydrogen; each R 8 are independently hydrogen or halogen; and R 11 and R 12 are each independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, -CN, -OR 9 .

[0255] In some embodiments, R 6 is C1-C6 alkyl, C1-C6 fluoroalkyl, or -L 2 -R 6a ;L 2 is absent, C1-C6 alkylene or -CHR 6b -;R 6a is a substituted or unsubstituted monocyclic 3-4 membered C3-C4 cycloalkyl, a substituted or unsubstituted monocyclic or bicyclic 5-10 membered C5-C 10 Cycloalkyl, substituted or unsubstituted 6-10 membered C6-C 10 Aryl, substituted or unsubstituted monocyclic 3-4 membered C2-C3 heterocycloalkyl, substituted or unsubstituted monocyclic or bicyclic 5-10 membered C4-C 10 Heterocycloalkyl, or substituted or unsubstituted 5-10 membered C1-C9 heteroaryl; R 6b is hydrogen, C1-C4 alkyl, C1-C4 fluoroalkyl, or substituted or unsubstituted monocyclic C3-C4 cycloalkyl; R 7 is hydrogen or C1-C6 alkyl.

[0256] In some embodiments, R 6 is C1-C6 alkyl, C1-C6 fluoroalkyl, or -L 2 -R 6a ;L 2 is absent, C1-C4 alkylene or -CHR 6b -;R 6a is substituted or unsubstituted cyclopropyl, substituted or unsubstituted cyclobutyl, substituted or unsubstituted azetidinyl, substituted or unsubstituted aziridine, substituted or unsubstituted oxetanyl, or substituted or unsubstituted theitanyl; R 6b is hydrogen, C1-C4 alkyl, C1-C4 fluoroalkyl, or substituted or unsubstituted monocyclic C3-C4 cycloalkyl; R 7 is hydrogen or C1-C6 alkyl.

[0257] In some embodiments, the compound has the structure of Formula (IX) or a pharmaceutically acceptable salt or solvate thereof:

[0258]

[0259] in:

[0260] A 1 C–R 8 ; and A 2 C–R 8 ;or

[0261] A 1 is N; and A 2 C–R 8 ;or

[0262] A 1 C–R 8 ; and A 2 is N;

[0263] R a and R c are independently hydrogen, halogen, –CN, –N(R 9 )2. –OR f , –CO2R 9 、–C(=O)N(R 9 )2, C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, substituted or unsubstituted monocyclic C3-C6 cycloalkyl, or substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl;

[0264] R f -L 1 -R g ;

[0265] L 1 is absent, or C1-C6 alkylene;

[0266] R g is hydrogen, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, -CO2R 9 , or -C(=O)N(R 9 )2, or substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl;

[0267] R 3 is hydrogen, C1-C4 alkyl, C1-C4 fluoroalkyl or C1-C4 heteroalkyl;

[0268] R 4 is hydrogen, halogen, C1-C4 alkyl or C1-C4 fluoroalkyl;

[0269] R5 is hydrogen, halogen, C1-C4 alkyl or C1-C4 fluoroalkyl;

[0270] R 6 is C1-C6 alkyl, C1-C6 fluoroalkyl, or -L 2 -R 6a ;

[0271] L 2 is absent, C1-C6 alkylene or -CHR 6b -;

[0272] R 6a is a substituted or unsubstituted monocyclic C3-C4 cycloalkyl, a substituted or unsubstituted monocyclic or bicyclic C5-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted monocyclic C2-C3 heterocycloalkyl, substituted or unsubstituted monocyclic or bicyclic C4-C 10 Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl;

[0273] R 6b is hydrogen, C1-C4 alkyl, C1-C4 fluoroalkyl, or substituted or unsubstituted monocyclic C3-C4 cycloalkyl;

[0274] R 7 is H or C1-C6 alkyl;

[0275] Each R 8 are independently hydrogen, halogen, C1-C6 alkyl, or C1-C6 fluoroalkyl;

[0276] R 11 and R 12 Each is independently hydrogen, halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, -CN, -OR 9 , –CO2R 9 、–C(=O)N(R 9 )2、–N(R 9 )2, or –NR 9 C(=O)R 10 , or substituted or unsubstituted monocyclic C3-C8 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl, or substituted or unsubstituted monocyclic C1-C5 heteroaryl;

[0277] Each R 9 are independently hydrogen, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl;

[0278] or two R on the same N atom 9together with the nitrogen atom to which they are attached, form a substituted or unsubstituted nitrogen-containing heterocyclic ring; and

[0279] Each R 10 are independently substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl.

[0280] In some embodiments, the compound has the structure of Formula (IXa) or (IXb) or a pharmaceutically acceptable salt or solvate thereof:

[0281]

[0282] In some embodiments, the compound has the structure of Formula (VIIIa-1) or (VIIIb-1) or a pharmaceutically acceptable salt or solvate thereof:

[0283]

[0284] In some embodiments, R 3 is hydrogen or -CH3; R 4 and R 5 Each is hydrogen; each R 8 are independently hydrogen or halogen; and R 11 and R 12 are each independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, -CN, -OR 9 .

[0285] In some embodiments, R 6 is C1-C6 alkyl, C1-C6 fluoroalkyl, or -L 2 -R 6a ;L 2 is absent, C1-C6 alkylene or -CHR 6b -;R 6a is a substituted or unsubstituted monocyclic 3-4 membered C3-C4 cycloalkyl, a substituted or unsubstituted monocyclic or bicyclic 5-10 membered C5-C 10 Cycloalkyl, substituted or unsubstituted 6-10 membered C6-C 10 Aryl, substituted or unsubstituted monocyclic 3-4 membered C2-C3 heterocycloalkyl, substituted or unsubstituted monocyclic or bicyclic 5-10 membered C4-C 10 Heterocycloalkyl, or substituted or unsubstituted 5-10 membered C1-C9 heteroaryl; R 6b is hydrogen, C1-C4 alkyl, C1-C4 fluoroalkyl, or substituted or unsubstituted monocyclic C3-C4 cycloalkyl; R 7 is hydrogen or C1-C6 alkyl.

[0286] In some embodiments, R 6 is C1-C6 alkyl, C1-C6 fluoroalkyl, or -L 2 -R 6a ;L 2 is absent, C1-C4 alkylene or -CHR 6b -;R 6a is substituted or unsubstituted cyclopropyl, substituted or unsubstituted cyclobutyl, substituted or unsubstituted azetidinyl, substituted or unsubstituted aziridine, substituted or unsubstituted oxetanyl, or substituted or unsubstituted theitanyl; R 6b is hydrogen, C1-C4 alkyl, C1-C4 fluoroalkyl, or substituted or unsubstituted monocyclic C3-C4 cycloalkyl; R 7 is hydrogen or C1-C6 alkyl.

[0287] In some embodiments, each R 9 are independently hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, or substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl; or two R on the same N atom 9 Together with the nitrogen atom to which they are attached, they form a substituted or unsubstituted nitrogen-containing heterocyclic ring; and each R 10 R is independently substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, or substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl. 9 are independently hydrogen, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl; or two R on the same N atom 9 Together with the nitrogen atom to which they are attached, they form a substituted or unsubstituted nitrogen-containing heterocyclic ring; and each R 10 is independently substituted or unsubstituted C1-C6 alkyl or substituted or unsubstituted C1-C6 fluoroalkyl. 9 are independently hydrogen, C1-C6 alkyl, or C1-C6 fluoroalkyl; or two R 9 Together with the nitrogen atom to which they are attached, they form a substituted or unsubstituted nitrogen-containing heterocyclic ring; and each R 10 are independently C1-C6 alkyl or C1-C6 fluoroalkyl.

[0288] In one aspect, provided herein is a compound of formula (A1) or a pharmaceutically acceptable salt or pharmaceutically acceptable solvate thereof:

[0289]

[0290] in:

[0291] Ring A is a carbocyclic ring or a heterocyclic ring;

[0292] X is N or C–R a ; Y is N or C–R b ; Z is N or C–R c ;

[0293] R L is hydrogen, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl;

[0294] R a 、R b and R c are independently hydrogen, halogen, –CN, –N(R 9 )2. –OR f , –CO2R 9 、–C(=O)N(R 9 )2, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 fluoroalkoxy, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted monocyclic carbocycle, or substituted or unsubstituted monocyclic heterocycle;

[0295] R f -L 1 -R g ;

[0296] L 1 is absent, C1-C6 alkylene, C1-C6 fluoroalkylene, or C1-C6 heteroalkylene;

[0297] R g is hydrogen, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, -CO2R 9 、-C(=O)N(R 9 ) 2, or substituted or unsubstituted monocyclic heterocycle;

[0298] R 1 and R 2 are independently hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C6 cycloalkyl, or substituted or unsubstituted C3-C5 heterocycloalkyl;

[0299] R 3is hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl;

[0300] R 4 and R 5 are independently hydrogen, halogen, –OR 9 ,–N(R 9 )2, –CN, –CO2R 9 、–C(=O)N(R 9 )2, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl;

[0301] R 6 is substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C1-C8 fluoroalkyl, substituted or unsubstituted C1-C8 heteroalkyl, or -L 2 -R 6a ;

[0302] L 2 is absent, substituted or unsubstituted C1-C8 alkylene, or -CHR 6b -;

[0303] R 6a is substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted C2-C 10 Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl;

[0304] R 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl;

[0305] R 7 is hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted C2-C 10 Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl;

[0306] or R 6 and R7 together with the nitrogen to which they are attached, form a substituted or unsubstituted N-containing heterocyclic ring;

[0307] Each R 8 、R 11 and R 12 are independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted monocyclic carbocycle, substituted or unsubstituted monocyclic heterocycle, -CN, -OR 9 、–C(=O)R 10 , –CO2R 9 、–C(=O)N(R 9 )2、–N(R 9 )2. –NR 9 C(=O)R 10 ,–NR 9 C(=O)OR 10 ,–NR 9 C(=O)N(R 9 )2, –C(R 9 )=N-OR 9 ,–SR 9 、–S(=O)R 9 ,–SO2R 9 , or –SO2N(R 9 )2;

[0308] or R 11 With adjacent R 8 And R 11 and adjacent R 8 The linked atoms together form a fused substituted or unsubstituted carbocyclic ring, or a fused substituted or unsubstituted heterocyclic ring;

[0309] Each R 9 are independently hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted monocyclic heteroaryl;

[0310] or two R on the same N atom 9 together with the nitrogen atom to which they are attached, form a substituted or unsubstituted nitrogen-containing heterocyclic ring;

[0311] Each R 10are independently substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted monocyclic heteroaryl; and

[0312] n is 0-3.

[0313] In some embodiments, R L is a substituted or unsubstituted C1-C6 alkyl group, or a substituted or unsubstituted C1-C6 fluoroalkyl group. L is C1-C6 alkyl or C1-C6 fluoroalkyl. L In some embodiments, R L is -CH3.

[0314] In some embodiments, R 1 and R 2 is independently hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl. 1 and R 2 is independently hydrogen or substituted or unsubstituted C1-C6 alkyl. 1 and R 2 are independently hydrogen or C1-C6 alkyl. 1 is hydrogen and R 2 is hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl. 1 is hydrogen and R 2 R is hydrogen or substituted or unsubstituted C1-C6 alkyl. 1 is hydrogen and R 2 is hydrogen or C1-C6 alkyl. 1 and R 2 Each is hydrogen.

[0315] In some embodiments, R 1 is hydrogen; R 2 is hydrogen or substituted or unsubstituted C1-C6 alkyl; and R L is a substituted or unsubstituted C1-C6 alkyl. 1 is hydrogen; R 2 is hydrogen; and R L is -CH3.

[0316] In some embodiments, X, Y, Z, R a 、R b 、R c As described for formula (I).

[0317] In some embodiments, X is C-R a ; Y is N; and Z is C–R c ; or X is CH; Y is N; and Z is C–R c ; or X is C–R a ; Y is N; and Z is CH; or X is N; Y is C–R b ; and Z is C–R c ; or X is C–R a ; Y is C–R b ; and Z is N; or X is N; Y is N; and Z is C–R c ; or X is C–R a ; Y is N; and Z is N. In some embodiments, X is N or CH; Y is N or CH; and Z is N or C-R c .

[0318] In some embodiments, R a 、R b and R c are independently hydrogen, halogen, –CN, –N(R 9 )2. –OR f , C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl; R f -L 1 -R g ;L 1 is absent or C1-C6 alkylene; and R g is hydrogen, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, or -CO2R 9 In some embodiments, R a 、R b and R c Each is independently hydrogen, -CN, -CH3, -CF3, -OCH3, -OCF3, -CO2CH3, -C(=O)NH2, -CONHCH3, or -C(=O)N(CH3)2, or cyclopropyl.

[0319] In some embodiments, Ring A, each R 8 、R 11 、R 12 and n are as described for formula (I).

[0320] In some embodiments, Ring A is phenyl, a monocyclic heteroaryl, or a bicyclic heteroaryl. In some embodiments, Ring A is phenyl or a monocyclic heteroaryl. In some embodiments, Ring A is phenyl; or Ring A is pyridyl; or Ring A is pyrazolyl, thiazolyl, isoxazolyl, or pyrimidinyl. In some embodiments, Ring A is phenyl or pyridyl. In some embodiments, Ring A is a bicyclic heteroaryl. In some embodiments, Ring A is benzimidazolyl, indazolyl, or benzoxadiazolyl.

[0321] In some embodiments, each R 8 are independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted monocyclic carbocycle, -CN, -OR 9 , –CO2R 9 、–C(=O)N(R 9 )2、–N(R 9 )2. –NR 9 C(=O)R 10 ,–SO2R 9 , or –SO2N(R 9 )2. In some embodiments, each R 8 is independently hydrogen, halogen, C1-C6 alkyl, or C1-C6 fluoroalkyl. 8 are independently hydrogen or halogen.

[0322] In some embodiments, R 11 is halogen, substituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted monocyclic carbocycle, substituted or unsubstituted monocyclic heterocycle, –CN, –OR 9 、–C(=O)R 10 , –CO2R 9 、–C(=O)N(R 9 )2、–N(R 9 )2. –NR 9 C(=O)R 10 ,–NR 9 C(=O)OR 10 ,–NR 9 C(=O)N(R 9 )2, –C(R 9 )=N-OR 9 ,–SR 9 、–S(=O)R 9 ,–SO2R 9 , or –SO2N(R 9 )2. In some embodiments, R 11is halogen, substituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted monocyclic carbocycle, substituted or unsubstituted monocyclic heterocycle, –CN, –OR 9 , –CO2R 9 、–C(=O)N(R 9 )2、–N(R 9 )2. –NR 9 C(=O)R 10 ,–NR 9 C(=O)OR 10 ,–NR 9 C(=O)N(R 9 )2, –C(R 9 )=N-OR 9 ,–SR 9 、–S(=O)R 9 ,–SO2R 9 , or –SO2N(R 9 )2. In some embodiments, R 11 Halogen, substituted C1-C6 alkyl, C1-C6 fluoroalkyl, –CN, –OR 9 , –CO2R 9 、–C(=O)N(R 9 )2、–N(R 9 )2, or –NR 9 C(=O)R 10 , substituted or unsubstituted monocyclic C3-C8 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl, or substituted or unsubstituted monocyclic C1-C5 heteroaryl. In some embodiments, R 11 is halogen, substituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, –CN, –OR 9 , –CO2R 9 、–C(=O)N(R 9 )2、–N(R 9 )2, or –NR 9 C(=O)R 10 , or a substituted or unsubstituted monocyclic carbocyclic ring. In some embodiments, R 11 is halogen, substituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, –CN, –OR 9 , –CO2R 9 、–C(=O)N(R 9 )2、–N(R 9 )2, or –NR 9 C(=O)R 10, or substituted or unsubstituted monocyclic C3-C8 cycloalkyl. In some embodiments, R 11 is halogen, substituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, –CN, –OR 9 , or substituted or unsubstituted monocyclic cycloalkyl. In some embodiments, R 11 is halogen, substituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, –CN, –OR 9 , or substituted or unsubstituted monocyclic C3-C8 cycloalkyl. In some embodiments, R 11 Halogen, substituted C1-C6 alkyl, C1-C6 fluoroalkyl, –CN, –OR 9 , or substituted or unsubstituted monocyclic C3-C8 cycloalkyl. In some embodiments, R 11 is halogen, substituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, –CN, –OR 9 In some embodiments, R 11 is halogen, C1-C6 fluoroalkyl, –CN, or –OR 9 In some embodiments, R 11 In some embodiments, R 11 In some embodiments, R 11 In some embodiments, R 11 In some embodiments, R 11 It is -Cl.

[0323] In some embodiments, R 11 With adjacent R 8 And R 11 and adjacent R 8 The atoms joined together form a fused substituted or unsubstituted carbocyclic ring, or a fused substituted or unsubstituted heterocyclic ring. 11 With adjacent R 8 And R 11 and adjacent R 8 The linked atoms together form a fused substituted or unsubstituted C3-C8 cycloalkyl, or a fused substituted or unsubstituted C2-C5 heterocycloalkyl.

[0324] In some embodiments, R 12is hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted monocyclic carbocycle, substituted or unsubstituted monocyclic heterocycle, –CN, –OR 9 , –CO2R 9 、–C(=O)N(R 9 )2、–N(R 9 )2. –NR 9 C(=O)R 10 ,–NR 9 C(=O)OR 10 ,–NR 9 C(=O)N(R 9 )2, –C(R 9 )=N-OR 9 ,–SR 9 、–S(=O)R 9 ,–SO2R 9 , or –SO2N(R 9 )2. In some embodiments, R 12 is hydrogen, halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, –CN, –OR 9 , –CO2R 9 、–C(=O)N(R 9 )2、–N(R 9 )2, or –NR 9 C(=O)R 10 , substituted or unsubstituted monocyclic C3-C8 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl, or substituted or unsubstituted monocyclic C1-C5 heteroaryl. In some embodiments, R 12 is hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, –CN, –OR 9 , or substituted or unsubstituted monocyclic C3-C8 cycloalkyl. In some embodiments, R 12 is hydrogen, halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, –CN, or –OR 9 In some embodiments, R 12 is hydrogen, -F, -Cl, -CN, -CH3, -CF3, -OCH3, -OCF3, or -OCHF2. In some embodiments, R 12 In some embodiments, R 12 is hydrogen, -F or -Cl.

[0325] In some embodiments, n is 0, 1, 2, or 3. In some embodiments, n is 0, 1, or 2. In some embodiments, n is 1, 2, or 3. In some embodiments, n is 2 or 3. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3.

[0326] In some embodiments, for Among them A 1 and A 2 Each independently is C–R 8 or N; and A 3 C–R 12 Or N. In some embodiments, for Among them A 2 C–R 8 Or N. In some embodiments, for In some embodiments, for In some embodiments, for In some embodiments, for In some embodiments, for In some embodiments, for where R 8 is hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl.

[0327] In some embodiments, R 6 and R 7 As described for formula (I).

[0328] In some embodiments, R 7 is hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C3-C4 cycloalkyl, or substituted or unsubstituted 3-membered or 4-membered heterocycloalkyl. 7 is hydrogen, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl. 7 is hydrogen or C1-C6 alkyl.

[0329] In some embodiments, R 6is substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C1-C8 fluoroalkyl, substituted or unsubstituted C1-C8 heteroalkyl, or -L 2 -R 6a ;L 2 is absent, substituted or unsubstituted C1-C8 alkylene, or -CHR 6b -;R 6a is substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted C2-C 10 Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl; R 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl.

[0330] In some embodiments, R 6 is a substituted or unsubstituted C1-C8 alkyl, a substituted or unsubstituted C1-C8 fluoroalkyl, or a substituted or unsubstituted C1-C8 heteroalkyl. 6 is C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C1-C6 heteroalkyl. 6 is a substituted or unsubstituted C1-C8 alkyl group, or a substituted or unsubstituted C1-C8 fluoroalkyl group. 6 is a substituted or unsubstituted C1-C6 alkyl group, or a substituted or unsubstituted C1-C6 fluoroalkyl group. 6 is a C1-C6 alkyl group or a C1-C6 fluoroalkyl group.

[0331] In some embodiments, R 6 -L 2 -R 6a .

[0332] In some embodiments, L 2 is absent, substituted or unsubstituted C1-C8 alkylene, or -CHR 6b -. In some embodiments, L 2 is absent, substituted or unsubstituted C1-C6 alkylene, or -CHR 6b -. In some embodiments, L 2 is absent, C1-C6 alkylene, or -CHR 6b -. In some embodiments, L 2 is absent, C1-C4 alkylene, or -CHR 6b -. In some embodiments, L 2is absent, -CH2-, -CH2CH2-, -CH2CH2CH2-, or -CHR 6b -. In some embodiments, L 2 is -CH2-, -CH2CH2-, -CH2CH2CH2-, or -CHR 6b -. In some embodiments, L 2 -CH2- or -CHR 6b -. In some embodiments, L 2 It is -CH2-, -CH(CH3)- or -CH(CF3)-.

[0333] In some embodiments, R 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl. 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C4 cycloalkyl. 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or C3-C4 cycloalkyl. 6b is hydrogen, C1-C4 alkyl, C1-C4 fluoroalkyl, or C3-C4 cycloalkyl. 6b is hydrogen, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CHF2, -CH2F, -CF3, cyclopropyl or cyclobutyl. In some embodiments, R 6b is hydrogen, -CH3, -CHF2, -CF3, cyclopropyl or cyclobutyl. In some embodiments, R 6b is hydrogen, -CH3, -CF3, or cyclopropyl. 6b is hydrogen, -CH3, or -CF3.

[0334] In some embodiments, R 6a is a substituted or unsubstituted monocyclic C3-C8 cycloalkyl, a substituted or unsubstituted polycyclic C5-C 10 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted indanyl, substituted or unsubstituted tetrahydronaphthyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl, substituted or unsubstituted polycyclic C5-C 10 In some embodiments, R 6a is a substituted or unsubstituted monocyclic C3-C6 cycloalkyl, a substituted or unsubstituted bridged C5-C 10Cycloalkyl, substituted or unsubstituted spiro C5-C 10 In some embodiments, R 6a is a substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl, a substituted or unsubstituted bridged C5-C 10 Heterocycloalkyl, substituted or unsubstituted spiro C5-C 10 heterocycloalkyl, substituted or unsubstituted monocyclic C1-C5 heteroaryl, or substituted or unsubstituted bicyclic C6-C9 heteroaryl.

[0335] In some embodiments, R 6a is a substituted or unsubstituted monocyclic C3-C4 cycloalkyl, a substituted or unsubstituted monocyclic or bicyclic C5-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted monocyclic C2-C3 heterocycloalkyl, substituted or unsubstituted monocyclic or bicyclic C4-C 10 In some embodiments, R 6a is a substituted or unsubstituted monocyclic 3-membered or 4-membered monocyclic cycloalkyl, a 3-membered or 4-membered monocyclic heterocycloalkyl, a substituted or unsubstituted monocyclic or bicyclic C5-C 10 cycloalkyl, or substituted or unsubstituted 5- to 10-membered heteroaryl.

[0336] In some embodiments, R 6a is a substituted or unsubstituted C3-C4 cycloalkyl, or a substituted or unsubstituted 3-membered or 4-membered C2-C3 heterocycloalkyl. 6a In some embodiments, R 6a is a substituted or unsubstituted C3-C4 cycloalkyl. 6a is substituted or unsubstituted cyclopropyl, or substituted or unsubstituted cyclobutyl. 6a is a substituted or unsubstituted cyclopropyl. In some embodiments, R 6a is a substituted or unsubstituted cyclobutyl group.

[0337] In some embodiments, R 6 is substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C1-C8 fluoroalkyl, substituted or unsubstituted C1-C8 heteroalkyl, or -L2 -R 6a ;L 2 is absent, substituted or unsubstituted C1-C8 alkylene, or -CHR 6b -;R 6a is substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted C2-C 10 heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl; and R 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl. 6 is C1-C8 alkyl, C1-C8 fluoroalkyl, substituted or unsubstituted C1-C8 heteroalkyl, or -L 2 -R 6a ;L 2 is absent, C1-C6 alkylene, or -CHR 6b -;R 6a is a substituted or unsubstituted monocyclic C3-C8 cycloalkyl, a substituted or unsubstituted polycyclic C5-C 10 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted indanyl, substituted or unsubstituted tetrahydronaphthyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl, substituted or unsubstituted polycyclic C5-C 10 heterocycloalkyl, substituted or unsubstituted monocyclic C1-C5 heteroaryl, or substituted or unsubstituted bicyclic C6-C9 heteroaryl; and R 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl.

[0338] In some embodiments, R 6 is C1-C6 alkyl, C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, or -L 2 -R 6a ;L 2 is absent, C1-C4 alkylene, or -CHR 6b -; and R 6b is hydrogen, C1-C4 alkyl, C1-C4 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl. 6a is a substituted or unsubstituted monocyclic C3-C6 cycloalkyl, a substituted or unsubstituted bridged C5-C 10 Cycloalkyl, substituted or unsubstituted spiro C5-C 10In some embodiments, R 6a is a substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl, a substituted or unsubstituted bridged C5-C 10 Heterocycloalkyl, substituted or unsubstituted spiro C5-C 10 heterocycloalkyl, substituted or unsubstituted monocyclic C1-C5 heteroaryl, or substituted or unsubstituted bicyclic C6-C9 heteroaryl.

[0339] In some embodiments, R 6 is C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 heteroalkyl, or -L 2 -R 6a ;L 2 is absent, C1-C4 alkylene, or -CHR 6b -;R 6a is a substituted or unsubstituted C3-C4 cycloalkyl group, or a substituted or unsubstituted 3-membered or 4-membered C2-C3 heterocycloalkyl group; and R 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C4 cycloalkyl. 6 is C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 heteroalkyl, or -L 2 -R 6a ;L 2 is absent, -CH2-, -CH2CH2-, -CH2CH2CH2-, or -CHR 6b -;R 6a is substituted or unsubstituted cyclopropyl, substituted or unsubstituted cyclobutyl, substituted or unsubstituted azetidinyl, or substituted or unsubstituted oxetanyl; and R 6b It is hydrogen, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CHF2, -CH2F, -CF3, cyclopropyl or cyclobutyl.

[0340] In some embodiments, R 6 and R 7 Together with the nitrogen to which they are attached, they form a substituted or unsubstituted N-containing heterocyclic ring. In some embodiments, R 6 and R 7 Together with the nitrogen to which they are attached, they form a substituted or unsubstituted N-containing heterocycloalkyl. In some embodiments, R 6 and R 7Together with the nitrogen to which they are attached, they form a substituted or unsubstituted monocyclic N-containing heterocycloalkyl group containing 1-2 N atoms, 0-2 O atoms and 0-1 S.

[0341] In some embodiments, X is N or CH;

[0342] Y is N or CH;

[0343] Z is N or C–R c ;

[0344] R c For hydrogen, halogen, –CN, –N(R 9 )2. –OR f , C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl;

[0345] R f -L 1 -R g ;

[0346] L 1 is absent, C1-C6 alkylene, or C1-C6 fluoroalkylene;

[0347] R g is hydrogen, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, -CO2R 9 , or -C(=O)N(R 9 )2;

[0348] R 1 is hydrogen;

[0349] R 2 is H or C1-C6 alkyl;

[0350] R L is a C1-C6 alkyl group or a C1-C6 fluoroalkyl group;

[0351] R 6 is C1-C8 alkyl, C1-C8 fluoroalkyl, or -L 2 -R 6a ;

[0352] L 2 is absent, C1-C6 alkylene, or -CHR 6b -;

[0353] R 6a is substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted C2-C 10Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl;

[0354] R 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl;

[0355] R 7 is H or C1-C6 alkyl;

[0356] or R 6 and R 7 Together with the nitrogen to which they are attached they form a substituted or unsubstituted heterocyclic ring.

[0357] In some embodiments, X is N or CH;

[0358] Y is N or CH;

[0359] Z is N or C–R c ;

[0360] R c is hydrogen, -F, -Cl, -CN, -CH3, -CF3, -OCH3, -OCH2CH3, -OCH2CHF2, -OCH2CF3, -OCH2CH2OCH3, -O-(cyclopropyl), -O-CH2-(cyclopropyl), -O-CH2-(phenyl), -OCH2CO2H, -OCH2CH2CO2H, -OCH2CH2CH2CO2H, -OCH2CO2CH3, -OCH2CH2CO2CH3, -OCH2CH2CH2CO2CH3, -OCH2CO2CH2CH3, -OCH2CH2CO2CH2CH3, or -OCH2CH2CH2CO2CH2CH3;

[0361] R 1 is hydrogen;

[0362] R 2 is hydrogen;

[0363] R L is a C1-C6 alkyl group;

[0364] R 6 is C1-C6 alkyl, C1-C6 fluoroalkyl, or -L 2 -R 6a ;

[0365] L 2 is absent, C1-C6 alkylene or -CHR 6b -;

[0366] R 6ais a substituted or unsubstituted monocyclic C3-C4 cycloalkyl, a substituted or unsubstituted monocyclic or bicyclic C5-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted monocyclic C2-C3 heterocycloalkyl, substituted or unsubstituted monocyclic or bicyclic C4-C 10 Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl;

[0367] R 6b is hydrogen, C1-C4 alkyl, C1-C4 fluoroalkyl, or substituted or unsubstituted monocyclic C3-C4 cycloalkyl;

[0368] R 7 is H or C1-C6 alkyl;

[0369] or R 6 and R 7 Together with the nitrogen to which they are attached they form a substituted or unsubstituted heterocyclic ring.

[0370] In some embodiments, the compound has the structure of Formula (A2) or a pharmaceutically acceptable salt or solvate thereof:

[0371]

[0372] in:

[0373] Ring A is phenyl or pyridyl;

[0374] R a and R c are independently hydrogen, halogen, –CN, –N(R 9 )2. –OR f , –CO2R 9 、–C(=O)N(R 9 )2, C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, substituted or unsubstituted monocyclic C3-C6 cycloalkyl, or substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl;

[0375] R f -L 1 -R g ;

[0376] L 1 is absent, or C1-C6 alkylene;

[0377] R g is hydrogen, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, -CO2R 9 , or -C(=O)N(R 9)2, or substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl;

[0378] R 1 is hydrogen;

[0379] R 2 is H or C1-C6 alkyl;

[0380] R L is a C1-C6 alkyl group or a C1-C6 fluoroalkyl group;

[0381] R 6 is C1-C6 alkyl, C1-C6 fluoroalkyl, or -L 2 -R 6a ;

[0382] L 2 is absent, C1-C6 alkylene or -CHR 6b -;

[0383] R 6a is a substituted or unsubstituted monocyclic C3-C4 cycloalkyl, a substituted or unsubstituted monocyclic or bicyclic C5-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted monocyclic C2-C3 heterocycloalkyl, substituted or unsubstituted monocyclic or bicyclic C4-C 10 Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl;

[0384] R 6b is hydrogen, C1-C4 alkyl, C1-C4 fluoroalkyl, or substituted or unsubstituted monocyclic C3-C4 cycloalkyl;

[0385] R 7 is H or C1-C6 alkyl;

[0386] Each R 8 are independently hydrogen, halogen, C1-C6 alkyl, or C1-C6 fluoroalkyl;

[0387] R 11 and R 12 Each is independently hydrogen, halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, -CN, -OR 9 , –CO2R 9 、–C(=O)N(R 9 )2、–N(R 9 )2, or –NR 9 C(=O)R 10, or substituted or unsubstituted monocyclic C3-C8 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl, or substituted or unsubstituted monocyclic C1-C5 heteroaryl;

[0388] Each R 9 are independently hydrogen, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl;

[0389] or two R on the same N atom 9 together with the nitrogen atom to which they are attached, form a substituted or unsubstituted nitrogen-containing heterocyclic ring; and

[0390] Each R 10 are independently substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl.

[0391] n is 0-3.

[0392] In some embodiments, each R 9 are independently hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, or substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl; or two R on the same N atom 9 Together with the nitrogen atom to which they are attached, they form a substituted or unsubstituted nitrogen-containing heterocyclic ring; and each R 10 R is independently substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, or substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl. 9 are independently hydrogen, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl; or two R on the same N atom 9 Together with the nitrogen atom to which they are attached, they form a substituted or unsubstituted nitrogen-containing heterocyclic ring; and each R 10 is independently substituted or unsubstituted C1-C6 alkyl or substituted or unsubstituted C1-C6 fluoroalkyl. 9 are independently hydrogen, C1-C6 alkyl, or C1-C6 fluoroalkyl; or two R 9 Together with the nitrogen atom to which they are attached, they form a substituted or unsubstituted nitrogen-containing heterocyclic ring; and each R 10 are independently C1-C6 alkyl or C1-C6 fluoroalkyl.

[0393] In some embodiments, the compounds described herein have the following structure:

[0394]

[0395] in,

[0396] As described in Table 1;

[0397] R 3 As described in Table 1;

[0398] R 4 As described in Table 1;

[0399] R c As described in Table 1; and

[0400] NR 6 R 7 As described in Table 1.

[0401] In some embodiments, the compounds described herein have the following structure:

[0402]

[0403] in,

[0404] As described in Table 2;

[0405] R c As described in Table 2; and

[0406] NR 6 R 7 As described in Table 2.

[0407] In some embodiments, the compounds described herein have the following structure:

[0408]

[0409] in,

[0410] R 11 As described in Table 3;

[0411] R 12 As described in Table 3; and

[0412] NR 6 R 7 As described in Table 3.

[0413] In some embodiments, the compounds described herein have the following structure:

[0414]

[0415] in,

[0416] As described in Table 4;

[0417] R c As described in Table 4; and

[0418] NR 6 R 7 As described in Table 4.

[0419] In some embodiments, the compounds described herein have the following structure:

[0420]

[0421] in,

[0422] R c As described in Table 5;

[0423] R d As described in Table 5;

[0424] R e As described in Table 5; and

[0425] NR 6 R 7 As described in Table 5.

[0426] In some embodiments, the compounds described herein have the following structure:

[0427]

[0428] in,

[0429] NR 6 R 7 As described in Table 6.

[0430] In some embodiments, the compounds described herein have the following structure:

[0431]

[0432] in,

[0433] R c As described in Table 7; and

[0434] NR 6 R 7 As described in Table 7.

[0435] In some embodiments, the compounds described herein have the following structure:

[0436]

[0437] in,

[0438] X is N or C-R as described herein a ,

[0439] Y is N or CH,

[0440] Z is N or C-R as described herein c ,

[0441] R d As described in this article

[0442] R e As described in this article and

[0443] R 6 and R 7 As described in this article.

[0444] In some embodiments, R d As described in this article

[0445] In some embodiments, X is N. In some embodiments, X is C-R a In some embodiments, X is CH.

[0446] In some embodiments, Y is N. In some embodiments, Y is CH.

[0447] In some embodiments, Z is N. In some embodiments, Z is C-R as described in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, or Table 7. c In some embodiments, Z is CH.

[0448] In some embodiments, X is CH, Y is N, and Z is C-R as described in Table 1, Table 2, Table 3, Table 4, or Table 5. c .

[0449] In some embodiments, X is CH, Y is CH, and Z is N.

[0450] In some embodiments, X is N, Y is CH, and Z is C-R as described in Table 7. c .

[0451] In some embodiments, R d As described in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6 or Table 7

[0452] In some embodiments, R d As described in Table 1, Table 5, Table 6 or Table 7 In some embodiments, Rd As described in Table 1 In some embodiments, R d for

[0453] In some embodiments, R d As described in Table 2 In some embodiments, R d for

[0454] In some embodiments, R d As described in Table 3 In some embodiments, R d for

[0455] In some embodiments, R d As shown in Table 4 In some embodiments, R d for

[0456] In some embodiments, R e As described in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6 or Table 7

[0457] In some embodiments, R e As described in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6 or Table 7 In some embodiments, Re is

[0458] In some embodiments, R e As described in Table 1, Table 2, Table 3, Table 4, Table 6 or Table 7 In some embodiments, R e for In some embodiments, R e for In some embodiments, R e for In some embodiments, R e for

[0459] In some embodiments, R e As described in Table 5 In some embodiments, R e for

[0460] In some embodiments, R 6 and R 7 As described in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, or Table 7. In some embodiments, As described in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, or Table 7. In some embodiments, for

[0461] In some embodiments, for

[0462] Any combination of the groups described above for the various variables is contemplated herein. Throughout the specification, groups and substituents thereof are chosen by one skilled in the art to provide stable moieties and compounds.

[0463] Exemplary compounds described herein include those described in the following table:

[0464] Table 1:

[0465]

[0466]

[0467]

[0468]

[0469]

[0470]

[0471]

[0472]

[0473]

[0474]

[0475]

[0476]

[0477]

[0478]

[0479]

[0480]

[0481]

[0482]

[0483]

[0484]

[0485]

[0486]

[0487]

[0488]

[0489]

[0490]

[0491] The compounds in Table 1 are named:

[0492] 1-1: 4-[(3S)-3-aminopyrrolidin-1-yl]-N,5-bis(3,5-dimethylphenyl)pyridine-3-carboxamide;

[0493] 1-3: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-(3-chloro-5-fluorophenyl)-5-(3,5-dimethylphenyl)pyridine-3-carboxamide;

[0494] 1-4: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-4-fluorophenyl)-N-(2-fluorophenyl)pyridine-3-carboxamide;

[0495] 1-7: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-cyanophenyl)-N-cyclohexylpyridine-3-carboxamide;

[0496] 1-8: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-cyanophenyl)-N-(1-methylcyclobutyl)pyridine-3-carboxamide;

[0497] 1-9: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-benzyl-5-(3-cyanophenyl)pyridine-3-carboxamide;

[0498] 1-10: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyanophenyl)-N-(4,4-difluorocyclohexyl)pyridine-3-carboxamide;

[0499] 1-11: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-dimethylcyclohexyl)-5-(3,5-dimethylphenyl)pyridine-3-carboxamide;

[0500] 1-12: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-dimethylphenyl)pyridine-3-carboxamide;

[0501] 1-13: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide;

[0502] 1-14: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclohexyl)-5-(3,5-dimethylphenyl)pyridine-3-carboxamide;

[0503] 1-15: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-fluoro-5-methylphenyl)-N-[1-(trifluoromethyl)cyclopentyl]pyridine-3-carboxamide;

[0504] 1-16: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0505] 1-17: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(2,3-dihydro-1H-inden-1-yl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide;

[0506] 1-18: N-(adamantan-2-yl)-4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide;

[0507] 1-19: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(1-ethylcyclobutyl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide;

[0508] 1-20: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,4,5-trifluorophenyl)pyridine-3-carboxamide;

[0509] 1-21: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0510] 1-22: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(3,3-dimethylcyclobutyl)pyridine-3-carboxamide;

[0511] 1-23: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopropyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0512] 1-24: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(1-cyclopropylethyl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide;

[0513] 1-25: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(dicyclopropylmethyl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide;

[0514] 1-26: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(cyclopropylmethyl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide;

[0515] 1-27: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-fluoro-5-methylphenyl)-N-(1-methyl-1H-pyrazol-3-yl)pyridine-3-carboxamide;

[0516] 1-28: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2,2,2-trifluoroethyl)pyridine-3-carboxamide;

[0517] 1-29: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-tert-butyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0518] 1-30: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0519] 1-31: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(pentan-3-yl)pyridine-3-carboxamide;

[0520] 1-32: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(1-methylcyclopropyl)methyl]pyridine-3-carboxamide;

[0521] 1-33: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(cyclobutylmethyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0522] 1-34: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(1-methylcyclobutyl)pyridine-3-carboxamide;

[0523] 1-35: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-(3,3-difluorocyclobutyl)pyridine-3-carboxamide;

[0524] 1-37: 4-[(3R,4R)-3-amino-4-fluoropyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0525] 1-38: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(3-methylbutan-2-yl)pyridine-3-carboxamide;

[0526] 1-39: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2,4-dimethylpentan-3-yl)pyridine-3-carboxamide;

[0527] 1-40: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(2-cyclopropylpropan-2-yl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0528] 1-41: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0529] 1-42: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(2,2-difluorocyclopropyl)methyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0530] 1-43: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(2,2-dimethylcyclopropyl)methyl]pyridine-3-carboxamide;

[0531] 1-44: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1R)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0532] 1-45: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(1,1,1-trifluoro-3-methylbutan-2-yl)pyridine-3-carboxamide;

[0533] 1-46: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2-methylpropyl)pyridine-3-carboxamide;

[0534] 1-47: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(1-fluorocyclobutyl)methyl]pyridine-3-carboxamide;

[0535] 1-48: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0536] 1-49: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0537] 1-50: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(3,3-difluorocyclobutyl)methyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0538] 1-51: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(dicyclopropylmethyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0539] 1-52: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[trans-2-fluorocyclohexyl]pyridine-3-carboxamide;

[0540] 1-53: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0541] 1-54: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0542] 1-55: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(trans-3-fluorocyclobutyl]pyridine-3-carboxamide;

[0543] 1-56: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(1-cyclobutyl-2,2,2-trifluoroethyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0544] 1-57: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2-methylbutyl)pyridine-3-carboxamide;

[0545] 1-58: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2-ethylbutyl)pyridine-3-carboxamide;

[0546] 1-59: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[cis-3-fluorocyclobutyl]pyridine-3-carboxamide;

[0547] 1-60: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(4,4,4-trifluorobutan-2-yl)pyridine-3-carboxamide;

[0548] 1-61: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-(dicyclopropylmethyl)pyridine-3-carboxamide;

[0549] 1-62: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2,2-difluoropropyl)pyridine-3-carboxamide;

[0550] 1-64: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0551] 1-65: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3-fluorophenyl)pyridine-3-carboxamide;

[0552] 1-66: 4-[(3S)-3-Aminopyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,4-difluorophenyl)pyridine-3-carboxamide;

[0553] 1-67: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0554] 1-68: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0555] 1-69: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0556] 1-70: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-N-(dicyclopropylmethyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0557] 1-71: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0558] 1-72: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(pentan-3-yl)pyridine-3-carboxamide;

[0559] 1-73: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-N-cycloheptyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0560] 1-74: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide;

[0561] 1-76: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(pentan-3-yl)pyridine-3-carboxamide;

[0562] 1-77: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0563] 1-78: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-cyclopentyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0564] 1-79: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0565] 1-80: 4-[(3S)-3-aminopyrrolidin-1-yl]-3-(3,5-difluorophenyl)-5-(piperidine-1-carbonyl)pyridine-2-carbonitrile;

[0566] 1-81: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-N-cyclohexyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0567] 1-82: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-N-cyclopentyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0568] 1-83: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[cis-2-fluorocyclohexyl]pyridine-3-carboxamide;

[0569] 1-84: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3-chlorophenyl)-6-cyanopyridine-3-carboxamide;

[0570] 1-85: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(2-methylpropyl)pyridine-3-carboxamide;

[0571] 1-86: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-(cyclopropylmethyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0572] 1-87: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-cyclobutyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0573] 1-88: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(oxan-4-yl)pyridine-3-carboxamide;

[0574] 1-89: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(oxan-3-yl)pyridine-3-carboxamide;

[0575] 1-90: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3-chloro-5-fluorophenyl)-6-cyanopyridine-3-carboxamide;

[0576] 1-91: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(propan-2-yl)pyridine-3-carboxamide;

[0577] 1-92: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(2,2,2-trifluoroethyl)pyridine-3-carboxamide;

[0578] 1-93: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-cyclohexyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0579] 1-94: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3-cyano-5-methoxyphenyl)pyridine-3-carboxamide;

[0580] 1-95: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide;

[0581] 1-96: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-N-[(1S)-1-cyclopropylethyl]pyridine-3-carboxamide;

[0582] 1-97: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1S)-1-phenylethyl]pyridine-3-carboxamide;

[0583] 1-98: 4-[(3S)-3-amino-3-(hydroxymethyl)pyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0584] 1-101: 4-[(3R,4R)-3-amino-4-fluoropyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0585] 1-103: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide;

[0586] 1-104: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1-methyl-1H-pyrazol-5-yl)methyl]pyridine-3-carboxamide;

[0587] 1-105: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1-methyl-1H-pyrazol-3-yl)methyl]pyridine-3-carboxamide;

[0588] 1-106: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1-methyl-1H-imidazol-2-yl)methyl]pyridine-3-carboxamide;

[0589] 1-107: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1-methyl-1H-pyrazol-4-yl)methyl]pyridine-3-carboxamide;

[0590] 1-108: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(pyrimidin-2-yl)methyl]pyridine-3-carboxamide;

[0591] 1-109: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(4-benzylpiperazine-1-carbonyl)-3-(3,5-difluorophenyl)pyridine-2-carbonitrile;

[0592] 1-110: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(3-phenylpropyl)pyridine-3-carboxamide;

[0593] 1-111: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(1-phenylpiperidin-4-yl)pyridine-3-carboxamide;

[0594] 1-112: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0595] 1-113: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(2,2-dimethyloxan-4-yl)pyridine-3-carboxamide;

[0596] 1-114: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1,2-oxazol-3-yl)methyl]pyridine-3-carboxamide;

[0597] 1-115: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2-hydroxyphenyl)methyl]pyridine-3-carboxamide;

[0598] 1-116: 4-[(3R)-3-amino-3-(methoxymethyl)pyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0599] 1-118: 4-[(3S)-3-amino-3-(2,2-difluoroethyl)pyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0600] 1-120: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-[3-(difluoromethoxy)phenyl]pyridine-3-carboxamide;

[0601] 1-122: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide;

[0602] 1-123: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide;

[0603] 1-124: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3-fluorophenyl)-6-methylpyridine-3-carboxamide;

[0604] 1-125: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide;

[0605] 1-126: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[1-(pyrimidin-2-yl)ethyl]pyridine-3-carboxamide;

[0606] 1-127: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-[3-(trifluoromethoxy)phenyl]pyridine-3-carboxamide;

[0607] 1-130: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;

[0608] 1-132: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[1-(1,2-oxazol-3-yl)ethyl]pyridine-3-carboxamide;

[0609] 1-133: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[1-(1-methyl-1H-1,2,3-triazol-4-yl)ethyl]pyridine-3-carboxamide;

[0610] 1-135: 4-[(3R,4R)-3-amino-4-fluoropyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0611] 1-137: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;

[0612] 1-138: 4-[(3R,4R)-3-amino-4-fluoropyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-cyano-N-[(1S)-1-cyclopropylethyl]pyridine-3-carboxamide;

[0613] 1-140: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0614] 1-141: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;

[0615] 1-143: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-[3-(difluoromethoxy)-5-fluorophenyl]pyridine-3-carboxamide;

[0616] 1-144: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;

[0617] 1-145: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-3,3-difluorocyclopentyl]-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;

[0618] 1-146: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide;

[0619] 1-147: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0620] 1-149: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-[3-(difluoromethoxy)phenyl]pyridine-3-carboxamide;

[0621] 1-150: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;

[0622] 1-151: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0623] 1-152: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;

[0624] 1-153: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methoxypyridine-3-carboxamide;

[0625] 1-154: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-6-methoxy-5-[3-(trifluoromethoxy)phenyl]pyridine-3-carboxamide;

[0626] 1-163: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(2,2-difluoro-2H-1,3-benzodioxol-4-yl)pyridine-3-carboxamide;

[0627] 1-164: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-[3-fluoro-5-(trifluoromethyl)phenyl]-6-methoxypyridine-3-carboxamide;

[0628] 1-165: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-[3-(difluoromethoxy)phenyl]-6-methoxypyridine-3-carboxamide;

[0629] 1-168: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-[3-(difluoromethoxy)phenyl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0630] 1-171: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0631] 1-172: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclobutyl)-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methylpyridine-3-carboxamide;

[0632] 1-173: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methylpyridine-3-carboxamide;

[0633] 1-174: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methylpyridine-3-carboxamide;

[0634] 1-175: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(2,2-difluoro-2H-1,3-benzodioxol-5-yl)pyridine-3-carboxamide;

[0635] 1-176: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-ethoxypyridine-3-carboxamide;

[0636] 1-177: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-6-(2,2-difluoroethoxy)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0637] 1-178: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-6-(cyclopropylmethoxy)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0638] 1-179: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-(2-methoxyethoxy)pyridine-3-carboxamide;

[0639] 1-180: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-[3-(difluoromethoxy)-5-fluorophenyl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0640] 1-181: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide;

[0641] 1-184: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(2,2-difluoro-2H-1,3-benzodioxol-4-yl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0642] 1-188: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0643] 1-189: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;

[0644] 1-190: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide;

[0645] 1-191: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyclopropyloxy-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0646] 1-192: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0647] 1-193: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-methoxy-N-[4-(trifluoromethyl)cyclohexyl]pyridine-3-carboxamide;

[0648] 1-194: 4-[(3S)-3-Aminopyrrolidin-1-yl]-N-(1-cyclopropyl-2,2,2-trifluoroethyl)-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;

[0649] 1-195: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-(trifluoromethyl)pyridine-3-carboxamide;

[0650] 1-196: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-6-methoxypyridine-3-carboxamide;

[0651] 1-197: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-N-[(1S)-1-cyclopropylethyl]-6-(trifluoromethyl)pyridine-3-carboxamide;

[0652] 1-198: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-(trifluoromethyl)pyridine-3-carboxamide;

[0653] 1-199: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;

[0654] 1-200: ethyl 2-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)acetate;

[0655] 1-201: ethyl 3-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)propanoate;

[0656] 1-202: ethyl 4-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)butanoate;

[0657] 1-203: 2-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)acetic acid

[0658] 1-204: 3-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)propanoic acid;

[0659] 1-205: 4-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)butanoic acid;

[0660] 1-209: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,4-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;

[0661] 1-210: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;

[0662] 1-211: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;

[0663] 1-212: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-(trifluoromethyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0664] 1-213: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-cyclohexyl-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;

[0665] 1-214: 4-[(3S)-3-Aminopyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;

[0666] 1-215: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-dichlorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;

[0667] 1-216: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-6-(trifluoromethyl)pyridine-3-carboxamide;

[0668] 1-217: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-6-(trifluoromethyl)pyridine-3-carboxamide;

[0669] 1-218: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-(cyclopropylmethyl)-5-(3,5-difluorophenyl)-N-methylpyridine-3-carboxamide;

[0670] 1-219: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-N-methylpyridine-3-carboxamide;

[0671] 1-222: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0672] 1-223: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(1-hydroxycyclopentyl)methyl]-6-methylpyridine-3-carboxamide;

[0673] 1-224: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(1-cyclopropyl-2-hydroxyethyl)-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide;

[0674] 1-225: 4-(3-aminopyrrolidin-1-yl)-6-cyano-5-(3,5-difluorophenyl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-carboxamide;

[0675] 1-226: 4-[(3S)-3-Aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-carboxamide;

[0676] 1-227: 4-[(3R)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0677] 1-228: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0678] 1-229: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methoxypyridine-3-carboxamide;

[0679] 1-230: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0680] 1-231: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0681] 1-232: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-[3-(difluoromethoxy)phenyl]-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0682] 1-233: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide;

[0683] 1-234: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-{3-fluorobicyclo[1.1.1]pentan-1-yl}pyridine-3-carboxamide;

[0684] 1-235: (3S)-1-[3-(3,5-difluorophenyl)-2-methoxy-5-(piperidine-1-carbonyl)pyridin-4-yl]pyrrolidin-3-amine;

[0685] 1-236: (3S)-1-[3-(3,5-difluorophenyl)-5-(4,4-difluoropiperidine-1-carbonyl)-2-methoxypyridin-4-yl]pyrrolidin-3-amine;

[0686] 1-237: (3S)-1-[3-(3,5-difluorophenyl)-5-(3,3-difluoropiperidine-1-carbonyl)-2-methoxypyridin-4-yl]pyrrolidin-3-amine;

[0687] 1-238: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methoxy-N-[(1,2-oxazol-3-yl)methyl]pyridine-3-carboxamide;

[0688] 1-239: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methoxy-N-[(1,2-oxazol-3-yl)methyl]pyridine-3-carboxamide;

[0689] 1-240: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methoxy-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide;

[0690] 1-241: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methoxy-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide;

[0691] 1-242: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methyl-N-[(1,2-oxazol-3-yl)methyl]pyridine-3-carboxamide;

[0692] 1-243: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methyl-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide;

[0693] 1-244: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-cyano-N-[(1,2-oxazol-3-yl)methyl]pyridine-3-carboxamide;

[0694] 1-245: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-cyano-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide;

[0695] 1-246: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-(2-hydroxyethoxy)pyridine-3-carboxamide;

[0696] 1-247: 2-({4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-{[(1S)-1-cyclopropylethyl]carbamoyl}-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)acetic acid;

[0697] 1-259: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,4-difluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0698] 1-260: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-chloro-3-fluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0699] 1-261: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-4-fluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0700] 1-262: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,4-difluorophenyl)-6-methoxypyridine-3-carboxamide;

[0701] 1-263: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-chloro-3-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methoxypyridine-3-carboxamide;

[0702] 1-264: 3-({4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-{[(1S)-1-cyclopropylethyl]carbamoyl}-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)propanoic acid;

[0703] 1-265: 4-({4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-{[(1S)-1-cyclopropylethyl]carbamoyl}-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)butanoic acid;

[0704] 1-266: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-[(oxetan-3-yl)methoxy]pyridine-3-carboxamide;

[0705] 1-267: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-(benzyloxy)-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0706] 1-268: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-N-(4,4-difluorocyclohexyl)-6-methylpyridine-3-carboxamide;

[0707] 1-269: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-N-(3,3-difluorocyclobutyl)-6-methylpyridine-3-carboxamide;

[0708] 1-272: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide;

[0709] 1-273: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-6-methoxypyridine-3-carboxamide;

[0710] 1-275: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0711] 1-276: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0712] 1-277: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-(4,4-difluorocyclohexyl)-6-methylpyridine-3-carboxamide;

[0713] 1-278: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-6-methylpyridine-3-carboxamide;

[0714] 1-279: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,4-difluorophenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0715] 1-280: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-N-[(1S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide;

[0716] 1-281: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyclopropyl-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0717] 1-282: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methoxypyridine-3-carboxamide;

[0718] 1-283: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0719] 1-284: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-(4,4-difluorocyclohexyl)-6-methoxypyridine-3-carboxamide;

[0720] 1-285: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-(3,3-difluorocyclobutyl)-6-methoxypyridine-3-carboxamide;

[0721] 1-286: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-6-methoxypyridine-3-carboxamide;

[0722] 1-287: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-4-fluorophenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0723] 1-288: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,4-difluorophenyl)-6-methylpyridine-3-carboxamide;

[0724] 1-289: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-4-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide;

[0725] 1-290: 4-[(3S)-3-Amino-3-methylpyrrolidin-1-yl]-6-cyclopropyl-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide.

[0726] In some embodiments, provided herein are pharmaceutically acceptable salts of the compounds described in Table 1.

[0727] Table 2:

[0728]

[0729]

[0730]

[0731]

[0732]

[0733] The compounds in Table 2 are named:

[0734] 1-5: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2'-cyano-N-(3-methylphenyl)-[3,4'-bipyridine]-5-carboxamide;

[0735] 1-6: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,5-dimethylphenyl)-2'-methyl-[3,4'-bipyridine]-5-carboxamide;

[0736] 1-121: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(1-methyl-1H-pyrazol-3-yl)pyridine-3-carboxamide;

[0737] 1-128: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(2-methyl-1,3-thiazol-5-yl)pyridine-3-carboxamide;

[0738] 1-129: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-[(1S)-1-cyclopropylethyl]-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide;

[0739] 1-131: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2',6'-dimethyl-[3,4'-bipyridine]-5-carboxamide;

[0740] 1-134: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(1,2-oxazol-4-yl)pyridine-3-carboxamide;

[0741] 1-142: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5'-fluoro-[3,3'-bipyridine]-5-carboxamide;

[0742] 1-148: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-6-methyl-5-(1-methyl-1H-pyrazol-4-yl)pyridine-3-carboxamide;

[0743] 1-155: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-6-methyl-5-[1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]pyridine-3-carboxamide;

[0744] 1-156: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(1-cyclopropyl-1H-pyrazol-4-yl)-N-[(1S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide;

[0745] 1-157: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2'-methoxy-2-methyl-[3,4'-bipyridine]-5-carboxamide;

[0746] 1-158: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5'-chloro-N-[(1S)-1-cyclopropylethyl]-2-methyl-[3,3'-bipyridine]-5-carboxamide;

[0747] 1-159: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2-methyl-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide;

[0748] 1-160: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5'-fluoro-2-methyl-[3,3'-bipyridine]-5-carboxamide;

[0749] 1-166: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2-methoxy-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide;

[0750] 1-167: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5'-chloro-N-[(1S)-1-cyclopropylethyl]-2-methoxy-[3,3'-bipyridine]-5-carboxamide;

[0751] 1-169: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-2'-(trifluoromethyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]-[3,4'-bipyridine]-5-carboxamide;

[0752] 1-170: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-2'-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]-[3,4'-bipyridine]-5-carboxamide;

[0753] 1-185: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-methoxy-5-(2-methylpyrimidin-5-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0754] 1-187: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0755] 1-206: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2'-ethoxy-2-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide;

[0756] 1-208: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2'-methoxy-2-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide;

[0757] 1-248: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-cyclopentyl-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide;

[0758] 1-249: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-(pentan-3-yl)-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide;

[0759] 1-250: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-(2-methylpropyl)-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide;

[0760] 1-251: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-butyl-2-cyano-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide;

[0761] 1-252: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-cyclohexyl-2'-methoxy-[3,4'-bipyridine]-5-carboxamide;

[0762] 1-253: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-2'-methoxy-N-(pentan-3-yl)-[3,4'-bipyridine]-5-carboxamide;

[0763] 1-254: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-cyclopentyl-2'-methoxy-[3,4'-bipyridine]-5-carboxamide;

[0764] 1-255: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-2'-methoxy-2-methyl-[3,4'-bipyridine]-5-carboxamide;

[0765] 1-256: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopentyl-2'-methoxy-2-methyl-[3,4'-bipyridine]-5-carboxamide;

[0766] 1-257: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-2-methyl-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide;

[0767] 1-258: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopentyl-2-methyl-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide;

[0768] 1-270: 4-[(3S)-3-Amino-3-methylpyrrolidin-1-yl]-2-cyano-2'-methoxy-N-(2-methylpropyl)-[3,4'-bipyridine]-5-carboxamide.

[0769] In some embodiments, provided herein are pharmaceutically acceptable salts of the compounds described in Table 2.

[0770] Table 3:

[0771]

[0772]

[0773]

[0774]

[0775] *The racemic compounds in Table 3 are named:

[0776] 2-1: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-ethyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[0777] 2-2: (3S)-3-methyl-1-[3-(4-methyl-1H-1,3-benzodiazol-2-yl)-5-(pyrrolidine-1-carbonyl)pyridin-4-yl]pyrrolidin-3-amine;

[0778] 2-3: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-ethyl-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[0779] 2-4: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopentyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[0780] 2-5: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-(oxolan-3-yl)pyridine-3-carboxamide;

[0781] 2-6: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-phenylpyridine-3-carboxamide;

[0782] 2-7: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-(2,2,2-trifluoroethyl)pyridine-3-carboxamide;

[0783] 2-8: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(2-methoxyethyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[0784] 2-9: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(2-hydroxyethyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[0785] 2-10: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-(2,2,2-trifluoroethyl)pyridine-3-carboxamide;

[0786] 2-11: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide;

[0787] 2-12: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopropyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[0788] 2-13: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(cyclopropylmethyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[0789] 2-14: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(1-cyclopropylethyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[0790] 2-15: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[0791] 2-16: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopentyl-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[0792] 2-17: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[0793] 2-18: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-[(2R)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide;

[0794] 2-19: (3S)-1-[3-(3,3-dimethylpyrrolidin-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine;

[0795] 2-20: (3S)-1-[3-(2,2-dimethylpyrrolidin-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine;

[0796] 2-21: (3S)-1-[3-(3,3-dimethylazetidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine;

[0797] 2-22: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopropyl-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[0798] 2-23: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(cyclopropylmethyl)-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[0799] 2-24: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-fluoro-1H-1,3-benzodiazol-2-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0800] 2-25: (3S)-1-[3-(3,3-difluoropyrrolidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine;

[0801] 2-26: (3S)-1-(3-{2-azatricyclic[3.3.1.13, 7 ]decane-2-carbonyl}-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl)-3-methylpyrrolidin-3-amine;

[0802] 2-27: (3S)-1-[3-(3-tert-butylpyrrolidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine;

[0803] 2-28: (3S)-1-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl}-3-methylpyrrolidin-3-amine;

[0804] 2-29: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[0805] 2-30: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(7-fluoro-4-methyl-1H-1,3-benzodiazol-2-yl)-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide;

[0806] 2-31: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(cyclobutylmethyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[0807] 2-32: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-(4,4,4-trifluorobutan-2-yl)pyridine-3-carboxamide;

[0808] 2-33: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[2.2.1]heptan-1-yl}-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[0809] 2-34: (3S)-1-[3-(2,3-dihydro-1H-indole-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine;

[0810] 2-35: (3S)-1-(3-{2-azabicyclo[2.2.2]octane-2-carbonyl}-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl)-3-methylpyrrolidin-3-amine;

[0811] 2-36: (3S)-3-methyl-1-[3-(4-methyl-1H-1,3-benzodiazol-2-yl)-5-[2-(propan-2-yl)pyrrolidine-1-carbonyl]pyridin-4-yl]pyrrolidin-3-amine;

[0812] 2-37: (3S)-1-{3-[(3aR)-octahydrocyclopenta[b]pyrrole-1-carbonyl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl}-3-methylpyrrolidin-3-amine;

[0813] 2-38: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[0814] 2-39: (3S)-1-(3-{5-azaspiro[2.4]heptane-5-carbonyl}-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl)-3-methylpyrrolidin-3-amine;

[0815] 2-40: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-[(2S)-1,1,1-trifluorobutan-2-yl]pyridine-3-carboxamide;

[0816] 2-41: (3S)-3-methyl-1-[3-(4-methyl-1H-1,3-benzodiazol-2-yl)-5-[(2S)-2-(trifluoromethyl)pyrrolidine-1-carbonyl]pyridin-4-yl]pyrrolidin-3-amine;

[0817] 2-42: (3S)-1-[3-(3-cyclopropylpyrrolidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine;

[0818] 2-43: (3S)-1-[3-(2-cyclopropylpyrrolidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine;

[0819] 2-44: (3S)-3-methyl-1-[3-(4-methyl-1H-1,3-benzodiazol-2-yl)-5-[3-(trifluoromethyl)pyrrolidine-1-carbonyl]pyridin-4-yl]pyrrolidin-3-amine;

[0820] 2-45: (3S)-1-(3-{2-azatricyclic[3.3.1.13, 7 ]decane-2-carbonyl}-5-(7-chloro-1H-1,3-benzodiazol-2-yl)pyridin-4-yl)-3-methylpyrrolidin-3-amine.

[0821] In some embodiments, provided herein are pharmaceutically acceptable salts of the compounds described in Table 3:

[0822] Table 4:

[0823]

[0824]

[0825]

[0826] The compounds in Table 4 are named:

[0827] 1-161: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(1-methyl-1H-indazol-6-yl)pyridine-3-carboxamide;

[0828] 1-162: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(1-methyl-1H-indazol-4-yl)pyridine-3-carboxamide;

[0829] 1-182: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-methoxy-5-(1-methyl-1H-1,3-benzodiazol-6-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0830] 1-183: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-methoxy-5-(1-methyl-1H-indazol-4-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[0831] 1-186: 4-[(3S)-3-Amino-3-methylpyrrolidin-1-yl]-5-(2,1,3-benzoxadiazol-5-yl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide.

[0832] In some embodiments, provided herein are pharmaceutically acceptable salts of the compounds described in Table 4.

[0833] Table 5:

[0834]

[0835]

[0836]

[0837] *Absolute stereochemistry has not yet been determined

[0838] The compounds in Table 5 are named:

[0839] 1-2: 4-[(3R)-3-aminopyrrolidin-1-yl]-N,5-bis(3,5-dimethylphenyl)pyridine-3-carboxamide;

[0840] 1-36: 4-[3-amino-3-(methoxymethyl)pyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0841] 1-63: 4-[3-(1-aminoethyl)azetidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0842] 1-75: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyanopyridine-3-carboxamide;

[0843] 1-99: 4-[(3R)-3-amino-3-(hydroxymethyl)pyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0844] 1-100: 4-[3-(1-aminoethyl)azetidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0845] 1-102: 4-[(3S,4S)-3-amino-4-fluoropyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0846] 1-117: 4-[(3S)-3-amino-3-(methoxymethyl)pyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0847] 1-119: 4-[(3R)-3-amino-3-(2,2-difluoroethyl)pyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0848] 1-136: 4-[(3S,4S)-3-amino-4-fluoropyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0849] 1-139: 4-[(3S,4S)-3-amino-4-fluoropyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-cyano-N-[(1S)-1-cyclopropylethyl]pyridine-3-carboxamide;

[0850] 1-220: 4-[(3S)-3-amino-3-(fluoromethyl)pyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0851] 1-221: 4-[(3R)-3-amino-3-(fluoromethyl)pyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[0852] 1-274: 4-[(3S)-3-Amino-3-methylpyrrolidin-1-yl]-5-bromo-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide.

[0853] In some embodiments, provided herein are pharmaceutically acceptable salts of the compounds described in Table 5.

[0854] Table 6:

[0855]

[0856]

[0857]

[0858] The compounds in Table 6 are named:

[0859] 3-1: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2-(3,5-difluorophenyl)pyridine-4-carboxamide;

[0860] 3-2: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-2-(3,5-difluorophenyl)pyridine-4-carboxamide;

[0861] 3-3: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-(3,5-difluorophenyl)-N-[(1S)-1-phenylethyl]pyridine-4-carboxamide;

[0862] 3-4: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(dicyclopropylmethyl)-2-(3,5-difluorophenyl)pyridine-4-carboxamide;

[0863] 3-5: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[2.2.1]heptane-1-yl}-2-(3,5-difluorophenyl)pyridine-4-carboxamide;

[0864] 3-6: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cycloheptyl-2-(3,5-difluorophenyl)pyridine-4-carboxamide;

[0865] 3-7: N-(adamantan-1-yl)-3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-(3,5-difluorophenyl)pyridine-4-carboxamide;

[0866] 3-8: 3-[(3S)-3-Amino-3-methylpyrrolidin-1-yl]-N-cyclopentyl-2-(3,5-difluorophenyl)pyridine-4-carboxamide.

[0867] In some embodiments, provided herein are pharmaceutically acceptable salts of the compounds described in Table 6.

[0868] Table 7:

[0869]

[0870]

[0871] The compounds in Table 7 are named:

[0872] 4-1: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-chloro-N-[(1S)-1-cyclopropylethyl]-4-(3,5-difluorophenyl)pyridine-2-carboxamide;

[0873] 4-2: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-4-(3,5-difluorophenyl)-5-methylpyridine-2-carboxamide;

[0874] 4-3: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-cyano-N-[(1S)-1-cyclopropylethyl]-4-(3,5-difluorophenyl)pyridine-2-carboxamide;

[0875] 4-4: methyl 5-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-{[(1S)-1-cyclopropylethyl]carbamoyl}-4-(3,5-difluorophenyl)pyridine-3-carboxylate;

[0876] 4-5: 3-[(3S)-3-Amino-3-methylpyrrolidin-1-yl]-N2-[(1S)-1-cyclopropylethyl]-4-(3,5-difluorophenyl)pyridine-2,5-dicarboxamide.

[0877] In some embodiments, provided herein are pharmaceutically acceptable salts of the compounds described in Table 7.

[0878] In one aspect, the compounds described herein are in the form of pharmaceutically acceptable salts. Similarly, active metabolites of these compounds having the same type of activity are also included within the scope of this disclosure. In addition, the compounds described herein may exist in unsolvated form as well as in solvated form with pharmaceutically acceptable solvents such as water, ethanol, etc. The solvated forms of the compounds presented herein are also considered to be disclosed herein.

[0879] As used herein, "pharmaceutically acceptable" refers to a substance such as a carrier or diluent that does not abrogate the biological activity or properties of the compound and is relatively non-toxic, i.e., the substance does not cause undesirable biological effects when administered to a subject or does not interact in a deleterious manner with any components of the composition in which it is contained.

[0880] The term "pharmaceutically acceptable salt" refers to a form of a therapeutically active agent that consists of a cationic form of the therapeutically active agent in combination with a suitable anion, or in alternative embodiments, consists of an anionic form of the therapeutically active agent in combination with a suitable cation. Handbook of Pharmaceutical Salts: Properties, Selection and Use. International Union of Pure and Applied Chemistry, Wiley-VCH 2002. SM Berge, LD Bigley, DC Monkhouse, J. Pharm. Sci. 1977, 66, 1-19. PH Stahl and CG Wermuth, eds., Handbook of Pharmaceutical Salts: Properties, Selection and Use, Weinheim / Zürich: Wiley-VCH / VHCA, 2002. Pharmaceutically acceptable salts are generally more soluble and dissolve more rapidly in gastric and intestinal fluids than non-ionic substances, and therefore are useful in solid dosage forms. Moreover, because its solubility is generally a function of pH, selective dissolution in one or another part of the digestive tract is possible, and this ability can be manipulated as an aspect of delayed and sustained release properties. Likewise, because salt-forming molecules can equilibrate with the neutral form, biological membrane passage can be modulated.

[0881] In some embodiments, a pharmaceutically acceptable salt is obtained by reacting a compound of formula (I) with an acid. In some embodiments, the compound of formula (I) (i.e., the free base form) is alkaline and reacts with an organic acid or an inorganic acid. Inorganic acids include, but are not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, and metaphosphoric acid. Organic acids include, but are not limited to, 1-hydroxy-2-naphthoic acid; 2,2-dichloroacetic acid; 2-hydroxyethanesulfonic acid; 2-oxoglutaric acid; 4-acetamidobenzoic acid; 4-aminosalicylic acid; acetic acid; adipic acid; ascorbic acid (L); aspartic acid (L); benzenesulfonic acid; benzoic acid; camphoric acid (+); camphor-10-sulfonic acid (+); caprylic acid (decanoic acid); caprylic acid (hexanoic acid); caprylic acid (octanoic acid); carbonic acid; cinnamic acid; citric acid; cyclamic acid; dodecyl sulfuric acid; ethane-1,2-disulfonic acid; ethanesulfonic acid; formic acid; fumaric acid; galactaric acid; dapoxetine Cholic acid; glucoheptonic acid (D); gluconic acid (D); glucuronic acid (D); glutamic acid; glutaric acid; glycerophosphate; glycolic acid; hippuric acid; isobutyric acid; lactic acid (DL); lactobionic acid; lauric acid; maleic acid; malic acid (-L); malonic acid; mandelic acid (DL); methanesulfonic acid; naphthalene-1,5-disulfonic acid; naphthalene-2-sulfonic acid; nicotinic acid; oleic acid; oxalic acid; palmitic acid; pamoic acid; phosphoric acid; propionic acid; pyroglutamic acid (-L); salicylic acid; sebacic acid; stearic acid; succinic acid; sulfuric acid; tartaric acid (+L); thiocyanic acid; toluenesulfonic acid (para); and undecylenic acid.

[0882] In some embodiments, the compound of formula (I) is prepared as a chloride salt, a sulfate salt, a bromide salt, a methanesulfonate salt, a maleate salt, a citrate salt, or a phosphate salt.

[0883] In some embodiments, pharmaceutically acceptable salts are obtained by reacting a compound of formula (I) with a base. In some embodiments, the compound of formula (I) is acidic and reacts with a base. In such cases, the acidic protons of the compound of formula (I) are replaced by metal ions such as lithium, sodium, potassium, magnesium, calcium or aluminum ions. In some cases, the compounds described herein are coordinated with an organic base, such as, but not limited to, ethanolamine, diethanolamine, triethanolamine, tromethamine, meglumine, N-methylglucamine, dicyclohexylamine, tris(hydroxymethyl)methylamine. In other cases, the compounds described herein form salts with amino acids such as, but not limited to, arginine and lysine. Acceptable inorganic bases for forming salts with compounds containing acidic protons include, but are not limited to, aluminum hydroxide, calcium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydroxide, lithium hydroxide, etc. In some embodiments, the compounds provided herein are prepared as sodium salts, calcium salts, potassium salts, magnesium salts, meglumine salts, N-methylglucamine salts or ammonium salts.

[0884] It should be understood that references to pharmaceutically acceptable salts include solvent addition forms. In some embodiments, solvates contain stoichiometric or non-stoichiometric amounts of solvent and are formed during crystallization with pharmaceutically acceptable solvents such as water, ethanol, and the like. Hydrates are formed when the solvent is water, or alcoholates are formed when the solvent is alcohol. Solvates of the compounds described herein are conveniently prepared or formed in the processes described herein. In addition, the compounds provided herein optionally exist in unsolvated as well as solvated forms.

[0885] The methods and formulations described herein include the use of N-oxides (where appropriate) or pharmaceutically acceptable salts of compounds having the structure of Formula (I), as well as active metabolites of these compounds having the same type of activity.

[0886] In some embodiments, sites on the organic group (e.g., alkyl group, aromatic ring) of the compound of formula (I) are susceptible to various metabolic reactions. Incorporating suitable substituents into the organic group will reduce, minimize or eliminate the metabolic pathways. In specific embodiments, by way of example only, suitable substituents for reducing or eliminating the sensitivity of the aromatic ring to metabolic reactions are halogen, deuterium, alkyl, haloalkyl groups or deuterated alkyl.

[0887] In another embodiment, the compounds described herein are labeled isotopically (e.g., with a radioisotope) or by other means, including but not limited to the use of chromophores or fluorescent moieties, bioluminescent labels, or chemiluminescent labels.

[0888] The compounds described herein include isotopically labeled compounds which are identical to those depicted in the various formulas and structures presented herein, except that one or more atoms are replaced by an atom with an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes that can be incorporated into the compounds of the present invention include isotopes of hydrogen, carbon, nitrogen, oxygen, sulfur, fluorine, chlorine, iodine, and phosphorus, for example, 2 H. 3 H. 13 C. 14 C. 15 N. 18 O. 17 O. 35 S. 18 F. 36 Cl, 123 I. 124 I. 125 I. 131 I. 32 P and 33 In one aspect, an isotopically labeled compound as described herein, for example, one in which a radioactive isotope such as 3H and 14 C are useful in drug and / or substrate tissue distribution assays. In one aspect, substitution with isotopes such as deuterium affords certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements.

[0889] In some embodiments, the compound of formula (I) has one or more stereocenters, and each stereocenter exists independently in the R or S configuration. In some embodiments, the compound of formula (I) exists in the R configuration. In some embodiments, the compound of formula (I) exists in the S configuration. The compounds proposed herein include all diastereomers, single enantiomers, atropisomers and epimer forms and suitable mixtures thereof. The compounds and methods provided herein include all cis (cis), trans (trans), syn (syn), anti (anti), entgegen (E) and zusammen (Z) isomers and suitable mixtures thereof.

[0890] If desired, a single stereoisomer is obtained by methods such as stereoselective synthesis and / or separation of stereoisomers via chiral chromatographic columns or separation of diastereomers by achiral or chiral chromatographic columns or crystallization and recrystallization in an appropriate solvent or solvent mixture. In certain embodiments, the compound of formula (I) is prepared as a single stereoisomer by reacting a racemic mixture of the compound with an optically active resolving agent to form a pair of diastereomeric compounds / salts, separating the diastereomers and recovering optically pure single enantiomers. In some embodiments, the covalent diastereomeric derivatives of the compounds described herein are used to separate single enantiomers. In another embodiment, diastereomers are separated by separation / resolvation techniques based on solubility differences. In other embodiments, separation of stereoisomers is carried out by chromatography or by forming diastereomeric salts and separating by recrystallization or chromatography or any combination thereof. Jean Jacques, Andre Collet, Samuel H. Wilen, “Enantiomers, Racemates and Resolutions”, John Wiley And Sons, Inc., 1981. In some embodiments, stereoisomers are obtained by stereoselective synthesis.

[0891] In some embodiments, the compounds described herein are prepared as prodrugs. "Prodrug" refers to an agent that is converted into a parent drug in vivo. Prodrugs are generally useful because they are easier to administer than the parent drug in some cases. For example, they can be bioavailable orally, while the parent drug cannot. Further or alternatively, the prodrug also has improved solubility in a pharmaceutical composition relative to the parent drug. In some embodiments, the design of the prodrug increases effective water solubility. Non-limiting examples of prodrugs are compounds described herein, which are administered as esters ("prodrugs") but are then metabolically hydrolyzed to provide an active entity. Another example of a prodrug is a short peptide (polyamino acid) bonded to an acid group, wherein the peptide is metabolized to expose an active portion. In certain embodiments, when administered in vivo, the prodrug is chemically converted into the biological, pharmaceutical, or therapeutically active form of the compound. In certain embodiments, the prodrug is enzymatically metabolized into the biological, pharmaceutical, or therapeutically active form of the compound by one or more steps or processes.

[0892] Prodrugs of the compounds described herein include, but are not limited to, esters, ethers, carbonates, thiocarbonates, N-acyl derivatives, N-acyloxyalkyl derivatives, N-alkyloxyacyl derivatives, quaternary ammonium derivatives of tertiary amines, N-Mannich bases, Schiff bases, amino acid conjugates, phosphate esters, and sulfonate esters. See, for example, Design of Prodrugs, Bundgaard, A., ed., Elseview, 1985, and Method in Enzymology, Widder, K. et al., eds.; Academic, 1985, vol. 42, p. 309-396; Bundgaard, H. "Design and Application of Prodrugs", in A Textbook of Drug Design and Development, Krosgaard-Larsen and H. Bundgaard, eds., 1991, Chapter 5, p. 113-191; and Bundgaard, H., Advanced Drug Delivery Review, 1992, 8, 1-38, each of which is incorporated herein by reference. In some embodiments, the hydroxyl groups of the compounds disclosed herein are used to form prodrugs, wherein the hydroxyl groups are incorporated into acyloxyalkyl esters, alkoxycarbonyloxyalkyl esters, alkyl esters, aryl esters, phosphate esters, glycolipids, ethers, and the like. In some embodiments, the hydroxyl group of the compounds disclosed herein is a prodrug, wherein the hydroxyl group is subsequently metabolized in vivo to provide a carboxylic acid group. In some embodiments, the carboxyl group is used to provide an ester or amide (i.e., a prodrug), which is subsequently metabolized in vivo to provide a carboxylic acid group. In some embodiments, the compounds described herein are prepared as alkyl ester prodrugs.

[0893] Prodrug forms of the compounds described herein, wherein the prodrug is metabolized in vivo to produce a compound of Formula (I) as described herein, are included within the scope of the claims. In some cases, some of the compounds described herein are prodrugs of another derivative or active compound.

[0894] In some embodiments, any of the hydroxyl, amino, and / or carboxylic acid groups are functionalized in a suitable manner to provide a prodrug moiety. In some embodiments, the prodrug moiety is as described above.

[0895] In additional or further embodiments, the compounds described herein are metabolized upon administration to an organism in need thereof to produce a metabolite, which is subsequently used to produce a desired effect, including a desired therapeutic effect.

[0896] A "metabolite" of a compound disclosed herein is a derivative of the compound formed when the compound is metabolized. The term "active metabolite" refers to a biologically active derivative of the compound formed when the compound is metabolized. As used herein, the term "metabolism" refers to the sum of the following processes (including but not limited to hydrolysis reactions and reactions catalyzed by enzymes) by which a specific substance is changed by an organism. Thus, an enzyme can produce a specific structural change in a compound. For example, cytochrome P450 catalyzes a variety of oxidation and reduction reactions, while UDP-glucuronyltransferase catalyzes the transfer of activated glucuronic acid molecules to aromatic alcohols, fatty alcohols, carboxylic acids, amines, and free sulfhydryl groups. Metabolites of compounds disclosed herein are optionally identified by administering the compound to a host and analyzing tissue samples from the host, or by incubating the compound with hepatocytes in vitro and analyzing the resulting compound.

[0897] In some cases, the heterocyclic ring can exist in tautomeric form. In this case, it will be understood that the structure of the compound is shown or named in one tautomeric form, but may also be shown or named in an alternative tautomeric form. Such alternative tautomeric forms are explicitly included in the present disclosure, for example, the structures shown below. For example, benzimidazole or imidazole may exist in the following tautomeric form:

[0898]

[0899] Synthesis of compounds

[0900] The compounds of formula (I) described herein are synthesized using standard synthetic techniques or using methods known in the art in combination with methods described herein.

[0901] Unless otherwise indicated, conventional methods of mass spectroscopy, NMR, and HPLC were used.

[0902] The compounds are prepared using standard organic chemistry techniques such as those described in, for example, March's Advanced Organic Chemistry, 6th Edition, John Wiley and Sons, Inc. Alternative reaction conditions for the synthetic transformations described herein may be used, such as variations in solvents, reaction temperatures, reaction times, and different chemical reagents and other reaction conditions.

[0903] In some embodiments, the compounds described herein are prepared as described in Scheme A.

[0904] Option A:

[0905]

[0906] Nucleophilic substitution of I by a protected aminopyrrolidine provides intermediate II, which is subsequently reacted with a boronic acid (R d B(OH)2) or its ester or organic trifluoroborate (R d BF3K) is converted to intermediate III by a Suzuki–Miyaura reaction. Aldehyde III is treated with an oxidizing agent (e.g., NaClO2) to generate the corresponding acid IV, which is coupled with an amine in the presence of a coupling agent such as HATU or 1-chloro-N,N,2-trimethyl-1-propenylamine (Ghosez reagent) to generate amide intermediate V. Alternatively, aldehyde II is treated with an oxidizing agent (e.g., NaClO2) to generate acid VII, which can react with an amine in the presence of a coupling agent (e.g., HATU) to generate amide intermediate VIII. This compound undergoes an organometallic coupling reaction, such as a Suzuki–Miyaura reaction, to generate compound V. The protecting group is removed using an appropriate deprotection method to obtain the final compound VI.

[0907] In some other embodiments, the compounds described herein are prepared as described in Scheme B.

[0908] Option B:

[0909]

[0910] Nucleophilic substitution of IX by a protected aminopyrrolidine provides intermediate X, which is halogenated to provide compound XI. d B(OH)2) or its ester or organic trifluoroborate (R dAn organometallic coupling reaction with BF3K, such as the Suzuki–Miyaura reaction, converts XI to intermediate XII. Compound XII is converted to nitrile XIII using an organometallic cyanidation reaction, which is treated with an oxidizing agent such as NaClO2 to produce acid XIV. This compound can react with an amine in the presence of a coupling agent (such as HATU) to produce amide XV. Alternatively, 4,6-dichloronicotinate XVII is converted to nitrile XVIII via an organometallic cyanidation reaction, which undergoes nucleophilic substitution with a protected aminopyrrolidine to produce intermediate XIX. This compound is then treated with a halogenating agent such as NBS or 1-bromopyrrolidine-2,5-dione to produce XX. Intermediate XX is converted to XXI using an organometallic coupling reaction (such as the Suzuki–Miyaura reaction), which is hydrolyzed in the presence of a base to acid XIV. Intermediate XIX can also be converted to acid XXV, which can then react with an amine to produce amide XXVI. Subsequent halogenation followed by an organometallic coupling reaction, such as the Suzuki-Miyaura reaction, produces intermediate XV. Intermediate XXVI is also synthesized using a different method. Nucleophilic substitution of XVII with a protected aminopyrrolidine yields intermediate XXII, which is hydrolyzed under alkaline conditions and then coupled with an appropriate amine to produce amide XXIII. This compound is subjected to organometallic carbonylation conditions, and the resulting ester XIV is converted to the corresponding amide, which can be readily dehydrated to form nitrile XXVI. Removal of the protecting group from intermediate XV using an appropriate deprotection method yields the final compound XVI.

[0911] In some other embodiments, the compounds described herein are prepared as described in Scheme C.

[0912] Option C:

[0913]

[0914] Nucleophilic substitution of IX by a protected aminopyrrolidine provides intermediate X, which is brominated to provide intermediate XI. Compound XI is then converted to intermediate XII via an organometallic coupling reaction (e.g., Suzuki-Miyaura reaction), which undergoes another organometallic coupling reaction to introduce R c The compound is treated with an oxidizing agent such as NaClO2 to generate acid XXIX, which can react with an amine in the presence of a coupling agent such as HATU or Ghosez reagent to generate amide XXX. Alternatively, protected aminopyrrolidine nucleophilically displaces 4,6-dichloronicotinate ester XVII to give intermediate XXXII, which is hydrolyzed under alkaline conditions and then coupled with an amine to generate amide XXXIII. This compound is converted to intermediate XXXIV by an organometallic coupling reaction to introduce Rc Group. Halogenation of intermediate XXXIV leads to the formation of intermediate XXXV, which can be converted into compound XXX by an organometallic coupling reaction (such as Suzuki-Miyaura reaction). Alternatively, 4,6-dichloronicotinate XVII is converted into XXXII, which is then converted into XXXVI by an organometallic coupling reaction and then halogenated to obtain compound XXVII. This compound is converted into intermediate XXXVIII by an organometallic coupling reaction (such as Suzuki-Miyaura reaction), which is hydrolyzed under alkaline conditions to generate acid XXIX. The protecting group of intermediate XXX is removed by using an appropriate deprotection method to obtain final compound XXXI.

[0915] In some other embodiments, the compounds described herein are prepared as described in Scheme D.

[0916] Plan D:

[0917]

[0918] Nucleophilic substitution of 4,6-dichloronicotinate ester XVII by a protected aminopyrrolidine provides intermediate XXXII, which is treated with an alkoxide in the presence or absence of an organometallic catalyst to produce compound XXXIX. Subsequent halogenation, followed by an organometallic coupling reaction, such as the Suzuki-Miyaura reaction, provides intermediate XLI. This compound is converted to acid XLII under alkaline conditions, which is coupled with an amine in the presence of a coupling agent such as HATU or Ghosez reagent to produce amide XLIII. The protecting group of intermediate XLIII is removed by using an appropriate deprotection method to provide the final compound XLIV. Alternatively, ester XXXII is converted to acid XLV under alkaline conditions, which is coupled with an amine in the presence of a coupling agent such as HATU or Ghosez reagent to produce amide XLVI. Subsequent halogenation, followed by an organometallic coupling reaction, such as the Suzuki-Miyaura reaction, provides intermediate XLVIII. Removal of the protecting group by using an appropriate deprotection method, followed by treatment with an alkoxide, leads to the formation of final compound XLIV.

[0919] In some other embodiments, the compounds described herein are prepared as described in Scheme E.

[0920] Plan E:

[0921]

[0922] Nucleophilic substitution of I with a protected aminopyrrolidine provides intermediate II, which is treated with 1,2-diaminobenzene in wet DMF, NMP, DMSO, or other solvents under atmospheric oxygen with or without Na2S2O5 by heating to produce benzimidazole LII. Subsequently, LII is converted to ester LIII via an organometallic carbonylation reaction. Alternatively, compound II can be converted to ester L via an organometallic carbonylation reaction, which is treated with 1,2-diaminobenzene in wet DMF, NMP, DMSO, or other solvents under atmospheric oxygen with or without Na2S2O5 to produce benzimidazole LIII. Alternatively, aldehyde I can be reacted with 1,2-diaminobenzene in wet DMF, NMP, DMSO, or other solvents under atmospheric oxygen with or without Na2S2O5 to provide imidazole LI, which is nucleophilically substituted with a protected aminopyrrolidine to produce intermediate LII. Subsequently, ester LIII is converted to acid LIV under basic conditions, which is treated with an amine in the presence of a coupling reagent such as HATU to generate amide LV. Removal of the protecting group using an appropriate deprotection method affords the final compound LVI.

[0923] In some other embodiments, the compounds described herein are prepared as described in Scheme F.

[0924] Plan F:

[0925]

[0926] Nucleophilic substitution of LVII by a protected aminopyrrolidine provides intermediate LVIII, which is converted to compound LIX via an organometallic coupling reaction (e.g., Suzuki–Miyaura reaction). Basic hydrolysis of ester LIX leads to the formation of acid LX, which reacts with an amine in the presence of an amide coupling agent (e.g., HATU) to generate intermediate LXI. Removal of the protecting group using an appropriate deprotection method affords the final compound LXII.

[0927] In some other embodiments, the compounds described herein are prepared as described in Scheme G.

[0928] Plan G:

[0929]

[0930] Transition-metal-catalyzed cyanation of bromo-pyridine LXIII provides nitrile intermediate LXIV, which is iodinated in the presence of a strong base such as LDA to produce LXV. Compound LXV is converted to intermediate LXVI via an organometallic coupling reaction such as the Suzuki–Miyaura reaction. Subsequent nucleophilic substitution with a protected aminopyrrolidine provides intermediate LXVII, which hydrolyzes to the acid LXVIII under basic conditions. Compound LXVIII is treated with an amine in the presence of a coupling agent such as HATU to produce the amide LXIX. Removal of the protecting group using an appropriate deprotection method yields the final compound LXX. Compound LXIX can be converted to intermediate LXXI via an organometallic coupling reaction such as the Suzuki–Miyaura reaction. Removal of the protecting group using an appropriate deprotection method yields the final compound LXXII.

[0931] In some embodiments, the compounds are prepared as described in the Examples.

[0932] Certain terms

[0933] Unless otherwise indicated, the following terms used in this application have the definitions given below. The use of the term "include" and other forms such as "comprising" is non-limiting. The section headings used herein are for organizational purposes only and should not be construed as limiting the subject matter described.

[0934] As used herein, C1-C x Including C1-C2, C1-C3...C1-C x By way of example only, a group referred to as "C1-C6" indicates that there are from one to six carbon atoms in the moiety, i.e., a group containing 1 carbon atom, 2 carbon atoms, 3 carbon atoms, or 4 carbon atoms. Thus, by way of example only, "C1-C4 alkyl" indicates that there are from one to four carbon atoms in the alkyl group, i.e., the alkyl group is selected from methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and tert-butyl.

[0935] An "alkyl" group refers to an aliphatic hydrocarbon group. An alkyl group is a branched or straight chain. In some embodiments, an "alkyl" group has 1 to 10 carbon atoms, i.e., C1-C 10Alkyl. Whenever it appears in this article, a numerical range such as "1 to 10" refers to each integer in the given range; for example, "1 to 10 carbon atoms" means that the alkyl group consists of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc. up to and including 10 carbon atoms, but this definition also includes the occurrence of the term "alkyl" without specifying a numerical range. In some embodiments, the alkyl is a C1-C6 alkyl. In one aspect, the alkyl is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl. Typical alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, neopentyl or hexyl.

[0936] An "alkylene" group refers to a divalent alkyl group. Any of the above-mentioned monovalent alkyl groups can be converted to an alkylene group by removing the second hydrogen atom from the alkyl group. In some embodiments, the alkylene group is a C1-C6 alkylene group. In other embodiments, the alkylene group is a C1-C4 alkylene group. Typical alkylene groups include, but are not limited to, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, and the like. In some embodiments, the alkylene group is -CH2-.

[0937] An "alkoxy" group refers to an (alkyl)O- group where alkyl is as defined herein.

[0938] The term "alkylamine" refers to -N(alkyl) x H y A group wherein x is 0 and y is 2, or wherein x is 1 and y is 1, or wherein x is 2 and y is 0.

[0939] "Hydroxyalkyl" refers to an alkyl group in which one hydrogen atom is replaced by a hydroxyl group. In some embodiments, the hydroxyalkyl group is a C1-C4 hydroxyalkyl group. Typical hydroxyalkyl groups include, but are not limited to, -CH2OH, -CH2CH2OH, -CH2CH2CH2OH, -CH2CH2CH2CH2OH, and the like.

[0940] "Aminoalkyl" refers to an alkyl group in which one hydrogen atom is replaced by an amino group. In some embodiments, the aminoalkyl group is a C1-C4 aminoalkyl group. Typical aminoalkyl groups include, but are not limited to, -CH2NH2, -CH2CH2NH2, -CH2CH2CH2NH2, -CH2CH2CH2NH2, etc.

[0941] The term "alkenyl" refers to a class of alkyl groups in which at least one carbon-carbon double bond is present. In one embodiment, the alkenyl group has the formula -C(R)=CR2, wherein R refers to the remainder of the alkenyl group, which may be the same or different. In some embodiments, R is H or an alkyl group. In some embodiments, the alkenyl group is selected from ethenyl, propenyl (i.e., allyl), butenyl, pentenyl, pentadienyl, and the like. Non-limiting examples of alkenyl groups include -CH=CH2, -C(CH3)=CH2, -CH=CHCH3, -C(CH3)=CHCH3, and -CH2CH=CH2.

[0942] The term "alkynyl" refers to a class of alkyl groups in which at least one carbon-carbon triple bond is present. In one embodiment, the alkenyl group has the formula -C≡CR, where R refers to the remainder of the alkynyl group. In some embodiments, R is H or an alkyl group. In some embodiments, the alkynyl group is selected from ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like. Non-limiting examples of alkynyl groups include -C≡CH, -C≡CCH3, -C≡CCH2CH3, and -CH2C≡CH.

[0943] The term "heteroalkyl" refers to an alkyl group in which one or more of the skeletal atoms of the alkyl group are selected from atoms other than carbon, e.g., oxygen, nitrogen (e.g., -NH-, -N(alkyl)-), sulfur, or a combination thereof. The heteroalkyl group is attached to the remainder of the molecule at a carbon atom of the heteroalkyl group. In one aspect, the heteroalkyl group is a C1-C6 heteroalkyl group.

[0944] The term "aromatic" refers to a planar ring having a delocalized π electron system containing 4n+2 π electrons, where n is an integer. The term "aromatic" includes carbocyclic aryl ("aryl," e.g., phenyl) and heterocyclic aryl (or "heteroaryl" or "heteroaromatic") groups (e.g., pyridine). The term includes monocyclic or fused-ring polycyclic (i.e., rings that share adjacent pairs of carbon atoms) groups.

[0945] The term "carbocyclic" or "carbocycle" refers to a ring or ring system in which the atoms comprising the ring backbone are all carbon atoms. Thus, the term distinguishes carbocycles from "heterocyclic" rings or "heterocycles" in which the ring backbone contains at least one atom other than carbon. In some embodiments, at least one of the two rings of a bicyclic carbocycle is aromatic. In some embodiments, both rings of a bicyclic carbocycle are aromatic. Carbocycles include aryl and cycloalkyl groups.

[0946] As used herein, the term "aryl" refers to an aromatic ring wherein each atom comprising the ring is a carbon atom. In one aspect, aryl is phenyl or naphthyl. In some embodiments, aryl is phenyl. In some embodiments, aryl is phenyl, naphthyl, indanyl, indenyl, or tetrahydronaphthyl. In some embodiments, aryl is C6-C 10Aryl. Depending on the structure, an aryl group is a monovalent or divalent group (ie, an arylene group).

[0947] The term "cycloalkyl" refers to a non-aromatic group of monocyclic or polycyclic aliphatic groups wherein each atom (i.e., skeleton atoms) constituting the ring is a carbon atom. In some embodiments, cycloalkyl is a spirocyclic or bridged ring compound. In some embodiments, cycloalkyl is optionally fused to an aromatic ring, and the point of attachment is on a carbon that is not an aromatic ring carbon atom. Cycloalkyl groups include groups with 3 to 10 ring atoms. In some embodiments, cycloalkyl groups are selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, spiro [2.2] pentyl, norbornyl, and bicyclo [1.1.1] pentyl. In some embodiments, cycloalkyl is C3-C6 cycloalkyl. In some embodiments, cycloalkyl is C3-C4 cycloalkyl.

[0948] The term "halo" or alternatively "halogen" or "halo" means fluoro, chloro, bromo or iodo. In some embodiments, halo is fluoro, chloro or bromo.

[0949] The term "fluoroalkyl" refers to an alkyl group in which one or more hydrogen atoms are replaced by fluorine atoms. In one aspect, the fluoroalkyl group is a C1-C6 fluoroalkyl group.

[0950] The term "heterocycle" or "heterocyclic" refers to heteroaromatic rings (also known as heteroaryls) and heterocycloalkyl rings containing one to four heteroatoms in the ring, wherein each heteroatom in the ring is selected from O, S, and N, and wherein each heterocyclic group has 3 to 10 atoms in its ring system, provided that no ring contains two adjacent O or S atoms. Non-aromatic heterocyclic groups (also known as heterocycloalkyls) include rings having 3 to 10 atoms in their ring system, while aromatic heterocyclic groups include rings having 5 to 10 atoms in their ring system. Heterocyclic groups include benzo-fused ring systems. Examples of non-aromatic heterocyclic groups are pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, oxazolidinone, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, thiooxanyl, piperazinyl, aziridinyl, azetidinyl, oxetanyl, thietanyl, homopiperidinyl, oxepinyl, thiepanyl, oxazepinyl, oxazepinyl, oxetan ... Base, diazepine thiazolinone yl, 1,2,3,6-tetrahydropyridinyl, pyrrolin-2-yl, pyrrolin-3-yl, indolinyl, 2H-pyranyl, 4H-pyranyl, dioxanyl, 1,3-dioxolane, pyrazolinyl, dithianyl, dithiolanyl, dihydropyranyl, dihydrothiophenyl, dihydrofuranyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, 3-azabicyclo[3.1.0]hexanyl, 3-azabicyclo[ 4.1.0] heptyl, 3H-indolyl, indolin-2-onyl, isoindolin-1-onyl, isoindolin-1,3-dione, 3,4-dihydroisoquinolin-1(2H)-onyl, 3,4-dihydroquinolin-2(1H)-onyl, isoindolin-1,3-disulfinyl, benzo[d]oxazol-2(3H)-onyl, 1H-benzo[d]imidazol-2(3H)-onyl, benzo[d]thiazol-2(3H)-onyl and quinolizinyl. Examples of aromatic heterocyclic groups are pyridyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, quinolyl, isoquinolyl, indolyl, benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl, phthalazinyl, pyridazinyl, triazinyl, isoindolyl, pteridinyl, purinyl, oxadiazolyl, thiadiazolyl, furazanyl, benzofurazanyl, benzothienyl, benzothiazolyl, benzoxazolyl, quinazolinyl, quinoxalinyl, naphthyridinyl and furopyridinyl. The above groups are C-attached (or C-attached) or N-attached (if such is possible). For example, groups derived from pyrrole include pyrrol-1-yl (N-attached) or pyrrol-3-yl (C-attached). In addition, the group derived from imidazole includes imidazole-1-yl or imidazole-3-yl (all N-connected) or imidazole-2-yl, imidazole-4-yl or imidazole-5-yl (all C-connected).Heterocyclic group includes benzo fused ring system.Non-aromatic heterocycle is optionally substituted by one or two oxo (=O) moieties, such as pyrrolidin-2-one.In some embodiments, at least one of the two rings of bicyclic heterocycle is aromatic.In some embodiments, both rings of bicyclic heterocycle are aromatic.

[0951] The term "heteroaryl" or alternatively "heteroaromatic" refers to an aryl group comprising one or more ring heteroatoms selected from nitrogen, oxygen, and sulfur. Illustrative examples of heteroaryl groups include monocyclic heteroaryls and bicyclic heteroaryls. Monocyclic heteroaryls include pyridyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, pyridazinyl, triazinyl, oxadiazolyl, thiadiazolyl, and furazanyl. Monocyclic heteroaryls include indolizine, indole, benzofuran, benzothiophene, indazole, benzimidazole, purine, quinolizine, quinoline, isoquinoline, cinnoline, phthalazine, quinazoline, quinoxaline, 1,8-naphthyridine, and pteridine. In some embodiments, the heteroaryl group contains 0-4 N atoms in the ring. In some embodiments, the heteroaryl group contains 1-4 N atoms in the ring. In some embodiments, the heteroaryl group contains 0-4 N atoms, 0-1 O atoms, and 0-1 S atoms in the ring. In some embodiments, the heteroaryl group contains 1-4 N atoms, 0-1 O atoms, and 0-1 S atoms in the ring. In some embodiments, the heteroaryl group is a C1-C9 heteroaryl group. In some embodiments, the monocyclic heteroaryl group is a C1-C5 heteroaryl group. In some embodiments, the monocyclic heteroaryl group is a 5-membered or 6-membered heteroaryl group. In some embodiments, the bicyclic heteroaryl group is a C6-C9 heteroaryl group.

[0952] "Heterocycloalkyl" refers to a cycloalkyl group that includes at least one heteroatom selected from nitrogen, oxygen, and sulfur. In some embodiments, the heterocycloalkyl group is fused to an aryl or heteroaryl group. In some embodiments, the heterocycloalkyl group is an oxazolidinone group, a pyrrolidinyl group, a tetrahydrofuranyl group, a tetrahydrothiophenyl group, a tetrahydropyranyl group, a tetrahydrothiopyranyl group, a piperidinyl group, a morpholinyl group, a thiomorpholinyl group, a piperazinyl group, a piperidin-2-one group, a pyrrolidine-2,5-disulfinyl group, a pyrrolidine-2,5-diketone group, a pyrrolidinone group, an imidazolidinyl group, an imidazolidin-2-one group, or a thiazolidin-2-one group. In one aspect, the heterocycloalkyl group is a C2-C 10 In another aspect, the heterocycloalkyl group is C4-C 10 Heterocycloalkyl. In some embodiments, heterocycloalkyl is monocyclic or bicyclic. In some embodiments, heterocycloalkyl is monocyclic and is a 3-, 4-, 5-, 6-, 7-, or 8-membered ring. In some embodiments, heterocycloalkyl is monocyclic and is a 3-, 4-, 5-, or 6-membered ring. In some embodiments, heterocycloalkyl is monocyclic and is a 3- or 4-membered ring. In some embodiments, heterocycloalkyl contains 0-2 N atoms in the ring. In some embodiments, heterocycloalkyl contains 0-2 N atoms, 0-2 O atoms, and 0-1 S atoms in the ring.

[0953] The term "bond" or "single bond" refers to a chemical bond between two atoms or moieties when the atoms connected by the bond are considered to be part of a larger substructure. In one aspect, when a group described herein is a bond, the group mentioned is absent, thereby allowing a bond to form between the remaining identified groups.

[0954] The term "moiety" refers to a specific segment or functional group of a molecule. A chemical moiety is typically a recognized chemical entity embedded in or attached to a molecule.

[0955] The term "optionally substituted" or "substituted" means that the referenced group is optionally substituted by one or more other groups individually and independently selected from the group consisting of halogen, -CN, -NH2, -NH(alkyl), -N(alkyl)2, -OH, -C02H, -C02alkyl, -C(=O)NH2, -C(=O)NH(alkyl), -C(=O)N(alkyl)2, -S(=O)2NH2, -S(=O)2NH(alkyl), -S(=O)2N(alkyl)2, alkyl, cycloalkyl, fluoroalkyl, heteroalkyl, alkoxy, fluoroalkoxy, heterocycloalkyl, aryl, heteroaryl, aryloxy, alkylthio, arylthio, alkyl sulfoxide, aryl sulfoxide, alkyl sulfone and aryl sulfone. In some other embodiments, the optional substituents are independently selected from halogen, -CN, -NH2, -NH(CH3), -N(CH3)2, -OH, -CO2H, -CO2(C1-C4 alkyl), -C(=O)NH2, -C(=O)NH(C1-C4 alkyl), -C(=O)N(C1-C4 alkyl)2, -S(=O)2NH2, -S(=O)2NH(C1-C4 alkyl), -S(=O)2N(C1-C4 alkyl)2, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 fluoroalkyl, C1-C4 heteroalkyl, C1-C4 alkoxy, C1-C4 fluoroalkoxy, -SC1-C4 alkyl, -S(=O)C1-C4 alkyl and -S(=O)2C1-C4 alkyl. In some embodiments, optional substituents are independently selected from halogen, -CN, -NH2, -OH, -NH(CH3), -N(CH3)2, -CH3, -CH2CH3, -CHF2, -CF3, -OCH3, -OCHF2, and -OCF3. In some embodiments, the substituted group is substituted by one or two of the aforementioned groups. In some embodiments, optional substituents on (acyclic or cyclic) aliphatic carbon atoms include oxo (=O).

[0956] In some embodiments, each substituted alkyl, substituted fluoroalkyl, substituted heteroalkyl, substituted carbocycle, and substituted heterocycle is replaced by one or more R s The group is substituted, the R sThe groups are independently selected from halogen, C1-C6 alkyl, monocyclic carbocycle, monocyclic heterocycle, -CN, -OR 21 、-CO2R 21 、-C(=O)N(R 21 )2、-N(R 21 )2、-NR 21 C(=O)R 22 、-SR 21 、-S(=O)R 22 、-SO2R 22 or -SO2N(R 21 )2; Each R 21 are independently selected from hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C2-C6 heterocycloalkyl, phenyl, benzyl, 5-membered heteroaryl and 6-membered heteroaryl; or two R 21 The groups together with the nitrogen atom to which they are attached form an N-containing heterocyclic ring; each R 22 Independently selected from C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C2-C6 heterocycloalkyl, phenyl, benzyl, 5-membered heteroaryl and 6-membered heteroaryl.

[0957]

[00146] The term "acceptable" with respect to a formulation, composition or ingredient, as used herein, means having no persistent detrimental effect on the general health of the subject being treated.

[0958] As used herein, the term "modulate" means interacting directly or indirectly with a target to alter the activity of the target, including, by way of example only, enhancing the activity of the target, inhibiting the activity of the target, limiting the activity of the target, or prolonging the activity of the target.

[0959] As used herein, the term "modulator" refers to a molecule that interacts directly or indirectly with a target. The interaction includes, but is not limited to, that of an agonist, partial agonist, inverse agonist, antagonist, degrader, or a combination thereof. In some embodiments, the modulator is an agonist.

[0960] As used herein, the terms "administer," "administer," and similar terms refer to methods that can be used to enable a compound or composition to be delivered to the desired site of biological action. These methods include, but are not limited to, oral routes, intraduodenal routes, parenteral injection (including intravenous, subcutaneous, intraperitoneal, intramuscular, intravascular, or infusion), topical, and rectal administration. Those skilled in the art are familiar with administration techniques that can be used with the compounds and methods described herein. In some embodiments, the compounds and compositions described herein are administered orally.

[0961] As used herein, the term "co-administration" or similar terms is intended to include administration of selected therapeutic agents to a single patient and is intended to include treatment regimens in which the agents are administered by the same or different routes of administration, or at the same or different times.

[0962] As used herein, the term "effective amount" or "therapeutically effective amount" refers to a sufficient amount of an administered agent or compound that will alleviate to some extent one or more symptoms of the disease or condition being treated. Results include alleviation and / or relief of the signs, symptoms, or causes of the disease, or any other desired change in a biological system. For example, an "effective amount" for therapeutic uses is the amount of a composition comprising a compound disclosed herein required to provide a clinically significant reduction in disease symptoms. An appropriate "effective" amount in any individual case is optionally determined using techniques such as dose escalation studies.

[0963] As used herein, the term "enhancing" means to increase or prolong, either in potency or duration, a desired effect. Thus, with respect to enhancing the effect of a therapeutic agent, the term "enhancing" refers to the ability to increase or prolong, either in potency or duration, the effect of another therapeutic agent on a system. As used herein, an "enhancing-effective amount" refers to an amount sufficient to enhance the effect of another therapeutic agent in a desired system.

[0964] The term "pharmaceutical combination" as used herein means a product obtained by mixing or combining more than one active ingredient, and includes fixed and non-fixed combinations of active ingredients. The term "fixed combination" means that the active ingredients, such as a compound of formula (I) or a pharmaceutically acceptable salt thereof, and an adjuvant (co-agent) are all administered to the patient simultaneously in the form of a single entity or dosage. The term "non-fixed combination" means that the active ingredients, such as a compound of formula (I) or a pharmaceutically acceptable salt thereof, and an adjuvant are administered to the patient simultaneously, jointly, or sequentially without specific time interval restrictions as separate entities, wherein such administration provides effective levels of the two compounds in the patient's body. The latter is also applicable to cocktail therapy, for example, the administration of three or more active ingredients.

[0965] The terms "article of manufacture" and "kit" are used synonymously.

[0966] The term "subject" or "patient" includes mammals. Examples of mammals include, but are not limited to, any member of the class Mammalia: humans, non-human primates such as chimpanzees, and other apes and monkeys; farm animals such as cattle, horses, sheep, goats, pigs; domestic animals such as rabbits, dogs, and cats; laboratory animals, including rodents such as rats, mice, and guinea pigs, etc. In one aspect, the mammal is a human.

[0967] As used herein, the term "treating" includes prophylactically and / or therapeutically alleviating, alleviating, or ameliorating at least one symptom of a disease or condition, preventing additional symptoms, inhibiting the disease or condition, e.g., arresting the development of the disease or condition, relieving the disease or condition, causing regression of the disease or condition, alleviating the condition caused by the disease or condition, or terminating the symptoms of the disease or condition.

[0968] Pharmaceutical composition

[0969] In some embodiments, the compounds described herein are formulated into pharmaceutical compositions. Pharmaceutical compositions are formulated in a conventional manner using one or more pharmaceutically acceptable inactive ingredients that facilitate processing of the active compound into pharmaceutically useful preparations. The appropriate formulation depends on the chosen route of administration. An overview of the pharmaceutical compositions described herein is found in, for example, Remington: The Science and Practice of Pharmacy, 19th Edition (Easton, Pa.: Mack Publishing Company, 1995); Hoover, John E., Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975; Liberman, HA and Lachman, L., eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, NY, 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, 7th Edition (Lippincott Williams & Wilkins 1999), which are incorporated herein by reference for their disclosures.

[0970] In some embodiments, the compounds described herein are administered alone or in combination with a pharmaceutically acceptable carrier, excipient, or diluent in a pharmaceutical composition. The administration of the compounds described herein and compositions can be achieved by any method that enables the compound to be delivered to the site of action. These methods include, but are not limited to, by enteral routes (including oral, gastric or duodenal feeding tubes, rectal suppositories, and rectal enemas), parenteral routes (injection or infusion, including intra-arterial, intracardiac, intradermal, intraduodenal, intramedullary, intramuscular, intraosseous, intraperitoneal, intrathecal, intravascular, intravenous, intravitreal, epidural, and subcutaneous), inhalation, transdermal, transmucosal, sublingual, buccal, and topical (including skin, dermis, enema, eye drops, ear drops, intranasal, vaginal) administration to deliver, but the most appropriate approach may depend on, for example, the condition and illness of the recipient. By way of example only, the compounds described herein can be topically applied to the area in need of treatment by, for example, local infusion, topical application such as cream or ointment, injection, catheter, or implant during surgery. Administration can also be by direct injection at the site of diseased tissue or organ.

[0971] In some embodiments, pharmaceutical compositions suitable for oral administration are presented as discrete units such as capsules, cachets, or tablets, each containing a predetermined amount of the active ingredient; as a powder or granules; as a solution or suspension in an aqueous or non-aqueous liquid; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion. In some embodiments, the active ingredient is presented as a pill, electuary, or paste.

[0972] Orally usable pharmaceutical compositions include tablets, push-fit capsules made of gelatin, and sealed soft capsules made of gelatin and plasticizers such as glycerol or sorbitol. Tablets can be prepared by compressing or molding them together with one or more auxiliary ingredients. Compressed tablets can be prepared by compressing a free-flowing form such as a powder or granules of active ingredient optionally mixed with a binder, an inert diluent or lubricant, a surfactant or a dispersant in a suitable machine. Molded tablets can be prepared by molding a mixture of powdered compounds moistened with an inert liquid diluent in a suitable machine. In some embodiments, the tablets are coated or scored and formulated to provide a slow or controlled release of the active ingredient therein. All formulations for oral administration should be suitable for the dosage to be administered. Push-fit capsules can contain active ingredients mixed with fillers such as lactose, binders such as starch, and / or lubricants such as talc or magnesium stearate, and optional stabilizers. In soft capsules, the active compound can be dissolved or suspended in a suitable liquid such as fatty oil, liquid paraffin or liquid polyethylene glycol. In some embodiments, a stabilizer is added. The lozenge core is provided with a suitable coating. To achieve this purpose, concentrated sugar solution can be used, which can optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbomer (carbopol) gel, polyethylene glycol and / or titanium dioxide, lacquer solution and a suitable organic solvent or solvent mixture. Dye or pigment can be added to tablet or lozenge coating to be used for identification or to characterize the different combinations of active compound dosage.

[0973] In some embodiments, the pharmaceutical composition is formulated for parenteral administration by injection, for example, by bolus injection or continuous infusion. The preparation for injection can be presented in, for example, an ampoule or a multidose container in a unit dosage form with the addition of a preservative. The composition can take the form of a suspension, solution or emulsion such as in an oily or aqueous vehicle, and can contain a formulation such as a suspending agent, a stabilizer and / or a dispersant. The composition can be presented in a unit dose or multidose container such as a sealed ampoule and a vial, and can be stored in powder form or under freeze-dried (lyophilized) conditions, only requiring the addition of a sterile liquid carrier, such as saline or sterile pyrogen-free water, just before use. Extemporaneous injection solutions and suspensions can be prepared by such sterile powders, granules and tablets described above.

[0974] Pharmaceutical compositions for parenteral administration include aqueous and non-aqueous (oily) sterile injection solutions of the active compound, which may contain antioxidants, buffers, bacteriostats, and solutes that make the preparation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions, which may contain suspending agents and thickening agents. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters such as ethyl oleate or triglycerides, or liposomes. Aqueous injection suspensions may contain substances that increase the viscosity of the suspension, such as sodium carboxymethylcellulose, sorbitol, or dextran. Optionally, the suspension may also contain suitable stabilizers or agents that increase the solubility of the compound to allow the preparation of highly concentrated solutions.

[0975] Pharmaceutical compositions can also be formulated as depot preparations. Such long-acting preparations can be administered by (e.g., subcutaneous or intramuscular) implantation or by intramuscular injection. Thus, for example, the compound can be formulated with a suitable polymeric material or hydrophobic material (e.g., an emulsion in an acceptable oil) or an ion exchange resin, or formulated as a slightly soluble derivative, e.g., as a slightly soluble salt.

[0976] For buccal or sublingual administration, the composition may take the form of tablets, lozenges, pastilles or gels formulated in conventional manner. Such compositions may contain the active ingredient in a flavored basis such as sucrose and acacia or tragacanth.

[0977] The pharmaceutical composition can be administered topically, i.e., by non-systemic administration. This includes external application of the compounds of the invention to the epidermis or buccal cavity, as well as instillation of such compounds into the ears, eyes, and nose, so that the compound does not significantly enter the bloodstream. In contrast, systemic administration refers to oral, intravenous, intraperitoneal, and intramuscular administration.

[0978] Pharmaceutical compositions suitable for topical administration include liquid or semi-liquid preparations suitable for penetration through the skin to the site of inflammation, such as gels, liniments, lotions, creams, ointments or pastes, and drops suitable for administration to the eyes, ears or nose. For topical administration, the active ingredient may constitute 0.001% to 10% w / w, for example 1% to 2% (weight) of the preparation.

[0979] Pharmaceutical compositions for administration by inhalation are conveniently delivered from insufflators, nebulizer pressurized packages, or other convenient means for delivering aerosol sprays. The pressurized package may contain a suitable propellant, such as dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, or other suitable gas. In the case of a pressurized aerosol, the dosage unit may be determined by providing a valve for delivering a metered amount. Alternatively, for administration by inhalation or insufflation, the pharmaceutical formulation may take the form of a dry powder composition, such as a powder mixture of the compound and a suitable powder base such as lactose or starch. The powder composition may be presented in unit dosage form, for example, in capsules, cartridges, gelatin, or blister packs from which the powder can be administered with the aid of an insufflator or insufflator.

[0980] It should be understood that in addition to the ingredients particularly mentioned above, the compounds and compositions described herein may include other agents conventional in the art having regard to the type of formulation in question, for example, those suitable for oral administration may include flavoring agents.

[0981] Dosage and treatment regimen

[0982] In one embodiment, a compound of formula (I) or a pharmaceutically acceptable salt thereof is used to prepare a medicament for treating a disease or condition in a mammal that would benefit from modulation of somatostatin activity. The method for treating any disease or condition described herein in a mammal in need of such treatment comprises administering to the mammal a pharmaceutical composition comprising at least one compound of formula (I) or a pharmaceutically acceptable salt, active metabolite, prodrug, or pharmaceutically acceptable solvate thereof in a therapeutically effective amount.

[0983] In certain embodiments, compositions containing the compounds described herein are administered for preventive and / or therapeutic treatments. In certain therapeutic applications, the composition is administered to a patient already suffering from the disease or condition in an amount sufficient to cure or at least partially prevent at least one symptom of the disease or condition. The amount effective for this use depends on the severity and progression of the disease or condition, previous treatment, the patient's health, weight, and response to the drug, and the judgment of the treating physician. The therapeutically effective amount is optionally determined by methods including, but not limited to, dose escalation and / or dose ranging clinical trials.

[0984] In preventive applications, a composition containing a compound as described herein is administered to a patient susceptible to or at risk of a particular disease, disorder, or condition. Such an amount is defined as a "prophylactically effective amount or dose." In this application, the precise amount also depends on the patient's health, weight, etc. When used for a patient, the effective amount for this application will depend on the severity and progression of the disease, disorder, or condition, previous treatment, the patient's health and response to the drug, and the judgment of the treating physician. In one aspect, preventive treatment comprises administering a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof to a mammal that has previously experienced at least one symptom of the disease to be treated and is currently in remission, so as to prevent the recurrence of the symptoms of the disease or condition.

[0985] In certain embodiments where the patient's condition does not improve, the compound may be administered chronically, i.e., for an extended period of time, including the patient's lifetime, in order to alleviate or otherwise control or limit the symptoms of the patient's disease or condition, at the discretion of the physician.

[0986] Once the patient's condition improves, a maintenance dose is administered, if necessary. Subsequently, in specific embodiments, the dosage or frequency of administration, or both, is reduced to a level at which the improved disease, disorder, or condition is maintained, depending on the changes in symptoms. However, in certain embodiments, patients require long-term intermittent treatment upon any recurrence of symptoms.

[0987] The amount of a given agent corresponding to such an amount will vary depending on factors such as the specific compound, the disease state and its severity, the characteristics of the subject or host requiring treatment (e.g., weight, sex), etc., but will still be determined according to the specific circumstances related to the case, which include, for example, the specific agent being administered, the route of administration, the condition being treated, and the subject or host being treated.

[0988] However, in general, the dosage employed for adult treatment is generally in the range of 0.01 mg to 2000 mg per day. In one embodiment, the desired dose is conveniently presented in a single dose or in divided doses administered simultaneously or at appropriate intervals, for example as 2, 3, 4 or more sub-doses per day.

[0989] In one embodiment, the daily dose suitable for a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, is from about 0.01 to about 50 mg / kg body weight. In some embodiments, the daily dose or the amount of active substance in the dosage form is lower or higher than the ranges indicated herein based on a number of variables associated with a single treatment regimen. In various embodiments, the daily dose and unit dose vary according to a number of variables, including but not limited to the activity of the compound used, the disease or condition to be treated, the mode of administration, the needs of the individual subject, the severity of the disease or condition to be treated, and the judgment of the physician.

[0990] Toxicity and therapeutic efficacy of such treatment regimens are determined by standard pharmaceutical procedures in cell cultures or experimental animals, including but not limited to LD 50 and ED 50 The dose ratio between toxic and therapeutic effects is the therapeutic index and is expressed as LD 50 With ED 50 In certain embodiments, the data obtained from cell culture assays and animal studies are used to formulate therapeutically effective daily dosage ranges and / or therapeutically effective unit doses for mammals, including humans. In some embodiments, the daily dose of the compounds described herein is within the range that includes the ED with minimal toxicity. 50 In certain embodiments, the daily dosage range and / or unit dosage varies within this range depending upon the dosage form employed and the route of administration utilized.

[0991] Any of the above aspects is a further embodiment wherein an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof is: (a) administered systemically to a mammal; and / or (b) administered orally to a mammal; and / or (c) administered intravenously to a mammal; and / or (d) administered by injection to a mammal; and / or (e) administered topically to a mammal; and / or (f) administered non-systemically or topically to a mammal.

[0992] Any of the above aspects are further embodiments comprising a single administration of an effective amount of the compound, including further embodiments wherein (i) the compound is administered once daily; or (ii) the compound is administered to a mammal multiple times over the course of a day.

[0993] Any of the above aspects is a further embodiment comprising multiple administrations of an effective amount of the compound, including further embodiments wherein (i) the compound is administered continuously or intermittently, such as in a single dose; (ii) the time between multiple administrations is every 6 hours; (iii) the compound is administered to the mammal every 8 hours; (iv) the compound is administered to the mammal every 12 hours; (v) the compound is administered to the mammal every 24 hours. In further or alternative embodiments, the method comprises a drug holiday, wherein the administration of the compound is temporarily suspended or the dose of the administered compound is temporarily reduced; at the end of the drug holiday, dosing of the compound is resumed. In one embodiment, the length of the drug holiday varies from 2 days to 1 year.

[0994] Combination therapy

[0995] In certain cases, it is appropriate to administer at least one compound of Formula (I) or a pharmaceutically acceptable salt thereof in combination with one or more other therapeutic agents.

[0996] In one embodiment, administration of an adjuvant enhances the therapeutic effectiveness of a compound described herein (i.e., the adjuvant has minimal therapeutic benefit on its own, but the overall therapeutic benefit to the patient is enhanced when combined with another therapeutic agent). Alternatively, in some embodiments, administering a compound described herein with another agent (also including a therapeutic regimen) that also has therapeutic benefit enhances the benefit experienced by the patient.

[0997] In a specific embodiment, a compound of Formula (I), or a pharmaceutically acceptable salt thereof, is co-administered with a second therapeutic agent, wherein the compound of Formula (I), or a pharmaceutically acceptable salt thereof, and the second therapeutic agent modulate different aspects of the disease, disorder or condition being treated, thereby providing a greater overall benefit than administration of either therapeutic agent alone.

[0998] In any case, regardless of the disease, disorder or condition being treated, the overall benefit experienced by the patient is simply additive of the two therapeutic agents, or the patient experiences a synergistic benefit.

[0999] For the combination therapies described herein, dosages of the co-administered compounds vary depending on the type of co-drug employed, the specific drug employed, the disease or condition being treated, etc. In additional embodiments, when a compound provided herein is co-administered with one or more additional therapeutic agents, it is administered simultaneously or sequentially with the one or more additional therapeutic agents.

[1000] In combination therapy, the multiple therapeutic agents (one of which is a compound described herein) are administered in any order or even simultaneously. If administered simultaneously, the multiple therapeutic agents are provided in a single unified form, or in multiple forms (e.g., as a single pill or as two separate pills), by way of example only.

[1001] Formula (I) compound or its pharmaceutically acceptable salt and conjoint therapy are applied before, during or after the disease or condition occurs, and the timing of applying the composition containing the compound is different. Therefore, in one embodiment, the compound as described herein is used as a prophylactic and is continuously applied to a subject with a developmental condition or disease tendency to prevent the occurrence of the disease or condition. In another embodiment, the compound and composition are applied to the subject as quickly as possible during or after the onset of symptoms. In a specific embodiment, after the onset of a disease or condition is detected or suspected, the compound as described herein is applied as quickly as possible where feasible, and continues for the duration necessary for treating the disease. In some embodiments, the duration required for treatment may vary, and the treatment duration is adjusted to suit the specific needs of each subject.

[1002] The present invention provides embodiments including but not limited to the following:

[1003] 1. A compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof:

[1004]

[1005] in:

[1006] Ring A is a carbocyclic ring or a heterocyclic ring;

[1007] X is N or C–R a ; Y is N or C–R b ; Z is N or C–R c ;

[1008] R a 、R b and R c are independently hydrogen, halogen, –CN, –N(R 9 )2. –OR f , –CO2R 9 、–C(=O)N(R 9 )2, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 fluoroalkoxy, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted monocyclic carbocycle, or substituted or unsubstituted monocyclic heterocycle;

[1009] R f-L 1 -R g ;

[1010] L 1 is absent, C1-C6 alkylene, C1-C6 fluoroalkylene, or C1-C6 heteroalkylene;

[1011] R g is hydrogen, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, -CO2R 9 , or -C(=O)N(R 9 ) 2. substituted or unsubstituted monocyclic heterocycle;

[1012] R 1 and R 2 are independently hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C6 cycloalkyl, or substituted or unsubstituted C3-C5 heterocycloalkyl;

[1013] R 3 For hydrogen, -CN, –CO2R 9 、–C(=O)N(R 9 )2, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl;

[1014] R 4 and R 5 are independently hydrogen, halogen, –OR 9 ,–N(R 9 )2, –CN, –CO2R 9 、–C(=O)N(R 9 )2, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl;

[1015] R 6 is substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C1-C8 fluoroalkyl, substituted or unsubstituted C1-C8 heteroalkyl, or -L 2 -R 6a ;

[1016] L 2 is absent, substituted or unsubstituted C1-C8 alkylene, or -CHR 6b-;

[1017] R 6a is substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted C2-C 10 Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl;

[1018] R 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl;

[1019] R 7 is hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted C2-C 10 Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl;

[1020] or R 6 and R 7 together with the nitrogen to which they are attached, form a substituted or unsubstituted N-containing heterocyclic ring;

[1021] Each R 8 、R 11 and R 12 are independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted monocyclic carbocycle, substituted or unsubstituted monocyclic heterocycle, -CN, -OR 9 、–C(=O)R 10 , –CO2R 9 、–C(=O)N(R 9 )2、–N(R 9 )2. –NR 9 C(=O)R 10 ,–NR 9 C(=O)OR 10 ,–NR 9 C(=O)N(R 9 )2, –C(R 9 )=N-OR 9 ,–SR 9 、–S(=O)R 9 ,–SO2R 9 , or –SO2N(R 9 )2;

[1022] or R 11 With adjacent R 8 And the R 11 and the adjacent R 8 The linked atoms together form a fused substituted or unsubstituted carbocyclic ring, or a fused substituted or unsubstituted heterocyclic ring;

[1023] Each R 9 are independently hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted monocyclic heteroaryl;

[1024] or two R on the same N atom 9 together with the nitrogen atom to which they are attached, form a substituted or unsubstituted nitrogen-containing heterocyclic ring;

[1025] Each R 10 are independently substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted monocyclic heteroaryl; and

[1026] n is 0-3.

[1027] 2. The compound according to embodiment 1, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1028] R 1 is hydrogen;

[1029] R 2 is H or C1-C6 alkyl;

[1030] R 3 is hydrogen, C1-C6 alkyl or C1-C6 fluoroalkyl; and

[1031] R 4 and R 5 Each is independently hydrogen, halogen, C1-C6 alkyl, or C1-C6 fluoroalkyl.

[1032] 3. The compound according to embodiment 2 or embodiment 3, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1033] R 1 and R 2 Each is hydrogen;

[1034] R 3 is hydrogen or -CH3; and

[1035] R 4 and R 5 Each is hydrogen.

[1036] 4. The compound according to embodiment 1, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has a structure of Formula (Ia) or (Ib) or a pharmaceutically acceptable salt or solvate thereof:

[1037]

[1038] 5. The compound according to any one of embodiments 1-4, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1039] X is C–R a ; Y is N; and Z is C–R c ;or

[1040] X is CH; Y is N; and Z is C–R c ;or

[1041] X is C–R a ; Y is N; and Z is CH; or

[1042] X is N; Y is C–R b ; and Z is C–R c ;or

[1043] X is C–R a ; Y is C–R b ; and Z is N; or

[1044] X is N; Y is N; and Z is C–R c ;or

[1045] X is C–R a ; Y is N; and Z is N.

[1046] 6. The compound according to any one of embodiments 1-4, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has a structure of Formula (IIa) or a pharmaceutically acceptable salt or solvate thereof:

[1047]

[1048] 7. The compound according to embodiment 6, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1049] Ring A is phenyl, monocyclic heteroaryl or bicyclic heteroaryl.

[1050] 8. The compound according to embodiment 6 or embodiment 7, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has the structure of formula (IIIa) or a pharmaceutically acceptable salt or solvate thereof:

[1051]

[1052] 9. The compound according to embodiment 6, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1053] Ring A is a monocyclic heteroaryl; and

[1054] n is 0, 1 or 2.

[1055] 10. The compound according to embodiment 9, wherein:

[1056] Ring A is pyrrolyl, furyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl or triazinyl.

[1057] 11. The compound according to embodiment 7, wherein:

[1058] Ring A is phenyl; or

[1059] Ring A is pyridyl; or

[1060] Ring A is pyrazolyl, thiazolyl, isoxazolyl, pyridinyl or pyrimidinyl.

[1061] 12. The compound according to embodiment 7, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has a structure of Formula (IVa) or a pharmaceutically acceptable salt or solvate thereof:

[1062]

[1063] in:

[1064] A 1 and A 2 Each independently is C–R 8 or N; and

[1065] A 3 C–R 12 or N.

[1066] 13. The compound of embodiment 12, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1067] A 1 C–R 8 ; A 2C–R 8 And A 3 C–R 12 ;or

[1068] A 1 N; A 2 C–R 8 , and A 3 C–R 12 ;or

[1069] A 1 C–R 8 ; A 2 is N, and A 3 C–R 12 ;or

[1070] A 1 C–R 8 ; A 2 C–R 8 , and A 3 is N.

[1071] 14. The compound according to embodiment 12, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has the structure of Formula (IVa-1) or a pharmaceutically acceptable salt or solvate thereof:

[1072]

[1073] in:

[1074] A 1 C–R 8 ; and A 2 C–R 8 ;or

[1075] A 1 is N; and A 2 C–R 8 ;or

[1076] A 1 C–R 8 ; and A 2 is N.

[1077] 15. The compound according to embodiment 12, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has the structure of Formula (IVa-2), Formula (IVa-3), Formula (IVa-4) or Formula (IVa-5), or a pharmaceutically acceptable salt or solvate thereof:

[1078]

[1079] 16. The compound according to embodiment 12, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has a structure of Formula (Va) or a pharmaceutically acceptable salt or solvate thereof:

[1080]

[1081] 17. The compound according to embodiment 16, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has a structure of Formula (Va-1) or Formula (Va-2) or a pharmaceutically acceptable salt or solvate thereof:

[1082]

[1083] 18. The compound of any one of embodiments 1-17, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1084] Each R 8 are independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, -CN, -OR 9 , –CO2R 9 、–C(=O)N(R 9 )2、–N(R 9 )2, or –NR 9 C(=O)R 10 .

[1085] 19. The compound of any one of embodiments 1-18, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1086] Each R 8 are independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl.

[1087] 20. The compound of any one of embodiments 1-19, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1088] Each R 8 are independently hydrogen or halogen.

[1089] 21. The compound according to embodiment 16, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has the structure of formula (Va-3) or a pharmaceutically acceptable salt or solvate thereof:

[1090]

[1091] 22. The compound of any one of embodiments 1-21, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1092] R 11 and R 12 are each independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, -CN, -OR 9 , –CO2R 9 、–C(=O)N(R 9 )2、–N(R 9 )2, or –NR 9 C(=O)R 10 , or a substituted or unsubstituted monocyclic carbocycle.

[1093] 23. The compound of any one of embodiments 1-22, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1094] R 11 and R 12 are each independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, -CN, -OR 9 , or a substituted or unsubstituted monocyclic cycloalkyl.

[1095] 24. The compound of any one of embodiments 1-23, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1096] R 11 and R 12 are each independently halogen.

[1097] 25. The compound according to embodiment 8, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has the structure of Formula (VIa) or a pharmaceutically acceptable salt or solvate thereof:

[1098]

[1099] in:

[1100] R 3 is hydrogen or -CH3;

[1101] R 8 is hydrogen or halogen;

[1102] R 11 and R 12 are each independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, -CN, -OR 9 ;

[1103] R c For hydrogen, halogen, –CN, –N(R9 )2. –OR f , –CO2R 9 、–C(=O)N(R 9 2. C1-C6

[1104] Alkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted monocyclic C3-C6 cycloalkyl, substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl;

[1105] R f -L 1 -R g ;

[1106] L 1 is absent, or C1-C6 alkylene; and

[1107] R g is hydrogen, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, -CO2R 9 、-C(=O)N(R 9 )2. Substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl.

[1108] 26. The compound of embodiment 25, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1109] R c For hydrogen, halogen, –CN, –N(R 9 )2. –OR f , C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl;

[1110] R f -L 1 -R g ;

[1111] L 1 is absent or C1-C6 alkylene; and

[1112] R g is hydrogen, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, or -CO2R 9 .

[1113] 27. The compound of embodiment 25 or embodiment 26, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1114] R 8 is hydrogen, -F or -Cl;

[1115] R 11 and R 12 are each independently hydrogen, -F, -Cl, -CN, -CH3, -CF3, -OCH3, -OCF3, or -OCHF2; and

[1116] R c For hydrogen, -F, -Cl, -CN, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH2CH2CH3, -CH2CH(CH3)2, -CH(CH3)(CH2CH3), -C(CH3)3, -CH2F, -CHF2, -CF3, -CH2CF3, -OCH3, -OCH2CH3, -OCF3, -OCH2CHF2, -OCH2CF3, -OCH2CH2OCH3, -O-(cyclopropyl), -O-CH2-(cyclopropyl), -O-CH2-(phenyl), -OCH2C O2H, -OCH2CH2CO2H, -OCH2CH2CH2CO2H, -OCH2CO2CH3, -OCH2CH2CO2CH3, -OCH2CH2CH2CO2CH3, -OCH2CO2CH2CH3, -OCH2CH2CO2CH2CH3, -OCH2CH2CO2CH2CH3, -OCH2CH2CH2CO2CH2CH3, -CO2CH3, -CO2CH2CH3, -C(=O)NH2, -CONHCH3, -C(=O)N(CH3)2, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, pyrrolidinyl, piperidinyl or morpholinyl.

[1117] 28. The compound according to any one of embodiments 25-27, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has a structure of Formula (VIa-1) or a pharmaceutically acceptable salt or solvate thereof:

[1118]

[1119] in:

[1120] R 3 is hydrogen or -CH3;

[1121] R c is hydrogen, -CN, -CH3, -CF3, -OCH3, -OCF3, -CO2CH3, -C(=O)NH2, -CONHCH3, or -C(=O)N(CH3)2; and

[1122] R 11 and R 12 Each is independently hydrogen, halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, -CN, or -OR9 .

[1123] 29. The compound according to any one of embodiments 1-7, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has the structure of Formula (VIIa) or a pharmaceutically acceptable salt or solvate thereof:

[1124]

[1125] in:

[1126] R 8 is hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl;

[1127] R c For hydrogen, halogen, –CN, –N(R 9 )2. –OR f , C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl;

[1128] R f -L 1 -R g ;

[1129] L 1 is absent or C1-C6 alkylene;

[1130] R g is hydrogen, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, or -CO2R 9 .

[1131] 30. The compound of any one of embodiments 1-29, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1132] R 7 is hydrogen, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl; and

[1133] R 6 is substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C1-C8 fluoroalkyl, substituted or unsubstituted C1-C8 heteroalkyl, or -L 2 -R 6a ;

[1134] L 2 is absent, substituted or unsubstituted C1-C8 alkylene, or -CHR 6b -;

[1135] R6a is substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted C2-C 10 Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl;

[1136] R 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl;

[1137] or R 6 and R 7 Together with the nitrogen to which they are attached they form a substituted or unsubstituted N-containing heterocycloalkyl.

[1138] 31. The compound of any one of embodiments 1-30, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1139] R 7 is H or C1-C6 alkyl.

[1140] 32. The compound of any one of embodiments 1-31, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1141] R 7 It is hydrogen or -CH3.

[1142] 33. The compound of any one of embodiments 30-32, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1143] R 6 is a substituted or unsubstituted C1-C8 alkyl group, a substituted or unsubstituted C1-C8 fluoroalkyl group, or a substituted or unsubstituted C1-C8 heteroalkyl group.

[1144] 34. The compound of any one of embodiments 30-32, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1145] R 6 is a C1-C6 alkyl group or a C1-C6 fluoroalkyl group.

[1146] 35. The compound of embodiment 34, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1147] R 6is -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH2CH2CH3, -CH2CH(CH3)2, -CH(CH3)(CH2CH3), -CH(CH2CH3)(CH2CH3), -CH(CH2CH2CH3)(CH 2CH3), -C(CH3)(CHCH3)2, -C(CH3)3, -CH2F, -CHF2, -CF3, -CH2CF3, -CH(CF3)(CH3), -CH(CF3)(CH2CH3), -CH2CF2CH3, or -CH(CH3)(CH2CF3).

[1148] 36. The compound of any one of embodiments 30-32, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1149] R 6 -L 2 -R 6a ;

[1150] R 6a is a substituted or unsubstituted monocyclic C3-C8 cycloalkyl, a substituted or unsubstituted polycyclic C5-C 10 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted indanyl, substituted or unsubstituted tetrahydronaphthyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl, substituted or unsubstituted polycyclic C5-C 10 heterocycloalkyl, substituted or unsubstituted monocyclic C1-C5 heteroaryl, or substituted or unsubstituted bicyclic C6-C9 heteroaryl.

[1151] 37. The compound of embodiment 36, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1152] R 6a is a substituted or unsubstituted monocyclic C3-C6 cycloalkyl, a substituted or unsubstituted bridged C5-C 10 Cycloalkyl, substituted or unsubstituted spiro C5-C 10 cycloalkyl, substituted or unsubstituted adamantyl, substituted or unsubstituted phenyl, substituted or unsubstituted indanyl, substituted or unsubstituted tetrahydronaphthyl, or substituted or unsubstituted naphthyl.

[1153] 38. The compound of embodiment 36, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1154] R 6a is a substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl, a substituted or unsubstituted bridged C5-C 10Heterocycloalkyl, substituted or unsubstituted spiro C5-C 10 heterocycloalkyl, substituted or unsubstituted monocyclic C1-C5 heteroaryl, or substituted or unsubstituted bicyclic C6-C9 heteroaryl.

[1155] 39. The compound of any one of embodiments 36-38, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1156] L 2 is absent, C1-C4 alkylene, or -CHR 6b -;and

[1157] R 6b is hydrogen, C1-C4 alkyl, C1-C4 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl.

[1158] 40. The compound of any one of embodiments 36-39, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1159] L 2 is absent, C1-C4 alkylene, or -CHR 6b -;

[1160] R 6a is a substituted or unsubstituted C3-C4 cycloalkyl group, or a substituted or unsubstituted 3-membered or 4-membered C2-C3 heterocycloalkyl group;

[1161] R 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C4 cycloalkyl.

[1162] 41. The compound of any one of embodiments 36-40, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1163] L 2 is absent, -CH2-, -CH2CH2-, -CH2CH2CH2-, or -CHR 6b -;

[1164] R 6a is substituted or unsubstituted cyclopropyl, substituted or unsubstituted cyclobutyl, substituted or unsubstituted azetidinyl, or substituted or unsubstituted oxetanyl;

[1165] R 6b It is hydrogen, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CHF2, -CH2F, -CF3, cyclopropyl or cyclobutyl.

[1166] 42. The compound of any one of embodiments 1-29, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1167] for

[1168] 43. The compound of any one of embodiments 1-42, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1169] Each R 9 are independently hydrogen, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl;

[1170] or two R on the same N atom 9 together with the nitrogen atom to which they are attached, form a substituted or unsubstituted nitrogen-containing heterocyclic ring; and

[1171] Each R 10 are independently substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl.

[1172] 44. The compound of embodiment 1, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1173] X is N or CH;

[1174] Y is N or CH;

[1175] Z is N or C–R c ;

[1176] R c For hydrogen, halogen, –CN, –N(R 9 )2. –OR f , C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl;

[1177] R f -L 1 -R g ;

[1178] L 1 is absent, C1-C6 alkylene, or C1-C6 fluoroalkylene;

[1179] R g is hydrogen, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, -CO2R 9 , or -C(=O)N(R 9 )2;

[1180] R 1 is hydrogen;

[1181] R 2 is H or C1-C6 alkyl;

[1182] R 3 is hydrogen, C1-C6 alkyl or C1-C6 fluoroalkyl;

[1183] R 4 is hydrogen, halogen, C1-C6 alkyl or C1-C6 fluoroalkyl;

[1184] R 5 is hydrogen, halogen, C1-C6 alkyl or C1-C6 fluoroalkyl;

[1185] R 6 is C1-C8 alkyl, C1-C8 fluoroalkyl, or -L 2 -R 6a ;

[1186] L 2 is absent, C1-C6 alkylene, or -CHR 6b -;

[1187] R 6a is substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted C2-C 10 Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl;

[1188] R 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl;

[1189] R 7 is H or C1-C6 alkyl;

[1190] or R 6 and R 7 Together with the nitrogen to which they are attached they form a substituted or unsubstituted heterocyclic ring.

[1191] 45. The compound of embodiment 1, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1192] X is N or CH;

[1193] Y is N or CH;

[1194] Z is N or C–R c ;

[1195] Rc is hydrogen, -CN, -CH3, -CF3, -OCH3, -OCF3, -CO2CH3, -C(=O)NH2, -CONHCH3, or -C(=O)N(CH3)2;

[1196] R 1 is hydrogen;

[1197] R 2 is hydrogen;

[1198] R 3 is hydrogen, -CH3, -CH2OH, -CH2OCH3, -CH2CH2F, -CH2CHF2, or -CH2CF3;

[1199] R 4 is hydrogen or F;

[1200] R 5 is hydrogen or F;

[1201] R 6 is C1-C6 alkyl, C1-C6 fluoroalkyl, or -L 2 -R 6a ;

[1202] L 2 is absent, C1-C6 alkylene or -CHR 6b -;

[1203] R 6a is a substituted or unsubstituted monocyclic C3-C4 cycloalkyl, a substituted or unsubstituted monocyclic or bicyclic C5-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted monocyclic C2-C3 heterocycloalkyl, substituted or unsubstituted monocyclic or bicyclic C4-C 10 Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl;

[1204] R 6b is hydrogen, C1-C4 alkyl, C1-C4 fluoroalkyl, or substituted or unsubstituted monocyclic C3-C4 cycloalkyl;

[1205] R 7 is H or C1-C6 alkyl;

[1206] or R 6 and R 7 Together with the nitrogen to which they are attached they form a substituted or unsubstituted heterocyclic ring.

[1207] 46. ​​The compound according to embodiment 1, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has the structure of Formula (VIII) or a pharmaceutically acceptable salt or solvate thereof:

[1208]

[1209] in:

[1210] Ring A is phenyl or pyridyl;

[1211] R a and R c are independently hydrogen, halogen, –CN, –N(R 9 )2. –OR f , –CO2R 9 、–C(=O)N(R 9 )2, C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, substituted or unsubstituted monocyclic C3-C6 cycloalkyl, or substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl;

[1212] R f -L 1 -R g ;

[1213] L 1 is absent, or C1-C6 alkylene;

[1214] R g is hydrogen, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, -CO2R 9 , or -C(=O)N(R 9 )2, or substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl;

[1215] R 1 is hydrogen;

[1216] R 2 is hydrogen or C1-C6 alkyl;

[1217] R 3 is hydrogen, C1-C4 alkyl, C1-C4 fluoroalkyl or C1-C4 heteroalkyl;

[1218] R 4 is hydrogen, halogen, C1-C4 alkyl or C1-C4 fluoroalkyl;

[1219] R 5 is hydrogen, halogen, C1-C4 alkyl or C1-C4 fluoroalkyl;

[1220] R 6is C1-C6 alkyl, C1-C6 fluoroalkyl, or -L 2 -R 6a ;

[1221] L 2 is absent, C1-C6 alkylene or -CHR 6b -;

[1222] R 6a is a substituted or unsubstituted monocyclic C3-C4 cycloalkyl, a substituted or unsubstituted monocyclic or bicyclic C5-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted monocyclic C2-C3 heterocycloalkyl, substituted or unsubstituted monocyclic or bicyclic C4-C 10 Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl;

[1223] R 6b is hydrogen, C1-C4 alkyl, C1-C4 fluoroalkyl, or substituted or unsubstituted monocyclic C3-C4 cycloalkyl;

[1224] R 7 is hydrogen or C1-C6 alkyl;

[1225] Each R 8 are independently hydrogen, halogen, C1-C6 alkyl, or C1-C6 fluoroalkyl;

[1226] R 11 and R 12 Each is independently hydrogen, halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, -CN, -OR 9 , –CO2R 9 、–C(=O)N(R 9 )2、–N(R 9 )2, or –NR 9 C(=O)R 10 , or substituted or unsubstituted monocyclic C3-C8 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted monocyclic C2-C5 heterocycloalkyl, or substituted or unsubstituted monocyclic C1-C5 heteroaryl;

[1227] Each R 9 are independently hydrogen, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl;

[1228] or two R on the same N atom 9 together with the nitrogen atom to which they are attached, form a substituted or unsubstituted nitrogen-containing heterocyclic ring; and

[1229] Each R 10are independently substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 fluoroalkyl.

[1230] n is 0-3.

[1231] 47. The compound according to embodiment 46, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has the structure of Formula (IXa-1) or a pharmaceutically acceptable salt or solvate thereof:

[1232]

[1233] in:

[1234] A 1 C–R 8 ; and A 2 C–R 8 ;or

[1235] A 1 is N; and A 2 C–R 8 ;or

[1236] A 1 C–R 8 ; and A 2 is N.

[1237] 48. The compound of embodiment 46 or embodiment 47, or a pharmaceutically acceptable salt or solvate thereof, wherein:

[1238] R 3 is hydrogen or -CH3;

[1239] R 4 and R 5 Each is hydrogen;

[1240] Each R 8 are independently hydrogen or halogen; and

[1241] R 11 and R 12 are each independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, -CN, -OR 9 .

[1242] 49. A compound selected from:

[1243] 1-1: 4-[(3S)-3-aminopyrrolidin-1-yl]-N,5-bis(3,5-dimethylphenyl)pyridine-3-carboxamide;

[1244] 1-3: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-(3-chloro-5-fluorophenyl)-5-(3,5-dimethylphenyl)pyridine-3-carboxamide;

[1245] 1-4: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-4-fluorophenyl)-N-(2-fluorophenyl)pyridine-3-carboxamide;

[1246] 1-7: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-cyanophenyl)-N-cyclohexylpyridine-3-carboxamide;

[1247] 1-8: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-cyanophenyl)-N-(1-methylcyclobutyl)pyridine-3-carboxamide;

[1248] 1-9: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-benzyl-5-(3-cyanophenyl)pyridine-3-carboxamide;

[1249] 1-10: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyanophenyl)-N-(4,4-difluorocyclohexyl)pyridine-3-carboxamide;

[1250] 1-11: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-dimethylcyclohexyl)-5-(3,5-dimethylphenyl)pyridine-3-carboxamide;

[1251] 1-12: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-dimethylphenyl)pyridine-3-carboxamide;

[1252] 1-13: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide;

[1253] 1-14: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclohexyl)-5-(3,5-dimethylphenyl)pyridine-3-carboxamide;

[1254] 1-15: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-fluoro-5-methylphenyl)-N-[1-(trifluoromethyl)cyclopentyl]pyridine-3-carboxamide;

[1255] 1-16: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1256] 1-17: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(2,3-dihydro-1H-inden-1-yl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide;

[1257] 1-18: N-(adamantan-2-yl)-4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide;

[1258] 1-19: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(1-ethylcyclobutyl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide;

[1259] 1-20: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,4,5-trifluorophenyl)pyridine-3-carboxamide;

[1260] 1-21: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1261] 1-22: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(3,3-dimethylcyclobutyl)pyridine-3-carboxamide;

[1262] 1-23: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopropyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1263] 1-24: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(1-cyclopropylethyl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide;

[1264] 1-25: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(dicyclopropylmethyl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide;

[1265] 1-26: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(cyclopropylmethyl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide;

[1266] 1-27: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-fluoro-5-methylphenyl)-N-(1-methyl-1H-pyrazol-3-yl)pyridine-3-carboxamide;

[1267] 1-28: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2,2,2-trifluoroethyl)pyridine-3-carboxamide;

[1268] 1-29: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-tert-butyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1269] 1-30: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1270] 1-31: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(pentan-3-yl)pyridine-3-carboxamide;

[1271] 1-32: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(1-methylcyclopropyl)methyl]pyridine-3-carboxamide;

[1272] 1-33: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(cyclobutylmethyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1273] 1-34: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(1-methylcyclobutyl)pyridine-3-carboxamide;

[1274] 1-35: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-(3,3-difluorocyclobutyl)pyridine-3-carboxamide;

[1275] 1-37: 4-[(3R,4R)-3-amino-4-fluoropyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1276] 1-38: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(3-methylbutan-2-yl)pyridine-3-carboxamide;

[1277] 1-39: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2,4-dimethylpentan-3-yl)pyridine-3-carboxamide;

[1278] 1-40: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(2-cyclopropylpropan-2-yl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1279] 1-41: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1280] 1-42: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(2,2-difluorocyclopropyl)methyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1281] 1-43: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(2,2-dimethylcyclopropyl)methyl]pyridine-3-carboxamide;

[1282] 1-44: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1R)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1283] 1-45: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(1,1,1-trifluoro-3-methylbutan-2-yl)pyridine-3-carboxamide;

[1284] 1-46: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2-methylpropyl)pyridine-3-carboxamide;

[1285] 1-47: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(1-fluorocyclobutyl)methyl]pyridine-3-carboxamide;

[1286] 1-48: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1287] 1-49: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1288] 1-50: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(3,3-difluorocyclobutyl)methyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1289] 1-51: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(dicyclopropylmethyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1290] 1-52: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[trans-2-fluorocyclohexyl]pyridine-3-carboxamide;

[1291] 1-53: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1292] 1-54: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1293] 1-55: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(trans-3-fluorocyclobutyl]pyridine-3-carboxamide;

[1294] 1-56: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(1-cyclobutyl-2,2,2-trifluoroethyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1295] 1-57: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2-methylbutyl)pyridine-3-carboxamide;

[1296] 1-58: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2-ethylbutyl)pyridine-3-carboxamide;

[1297] 1-59: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[cis-3-fluorocyclobutyl]pyridine-3-carboxamide;

[1298] 1-60: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(4,4,4-trifluorobutan-2-yl)pyridine-3-carboxamide;

[1299] 1-61: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-(dicyclopropylmethyl)pyridine-3-carboxamide;

[1300] 1-62: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2,2-difluoropropyl)pyridine-3-carboxamide;

[1301] 1-64: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1302] 1-65: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3-fluorophenyl)pyridine-3-carboxamide;

[1303] 1-66: 4-[(3S)-3-Aminopyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,4-difluorophenyl)pyridine-3-carboxamide;

[1304] 1-67: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1305] 1-68: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1306] 1-69: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1307] 1-70: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-N-(dicyclopropylmethyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1308] 1-71: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1309] 1-72: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(pentan-3-yl)pyridine-3-carboxamide;

[1310] 1-73: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-N-cycloheptyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1311] 1-74: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide;

[1312] 1-76: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(pentan-3-yl)pyridine-3-carboxamide;

[1313] 1-77: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1314] 1-78: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-cyclopentyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1315] 1-79: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1316] 1-80: 4-[(3S)-3-aminopyrrolidin-1-yl]-3-(3,5-difluorophenyl)-5-(piperidine-1-carbonyl)pyridine-2-carbonitrile;

[1317] 1-81: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-N-cyclohexyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1318] 1-82: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-N-cyclopentyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1319] 1-83: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[cis-2-fluorocyclohexyl]pyridine-3-carboxamide;

[1320] 1-84: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3-chlorophenyl)-6-cyanopyridine-3-carboxamide;

[1321] 1-85: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(2-methylpropyl)pyridine-3-carboxamide;

[1322] 1-86: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-(cyclopropylmethyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1323] 1-87: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-cyclobutyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1324] 1-88: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(oxan-4-yl)pyridine-3-carboxamide;

[1325] 1-89: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(oxan-3-yl)pyridine-3-carboxamide;

[1326] 1-90: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3-chloro-5-fluorophenyl)-6-cyanopyridine-3-carboxamide;

[1327] 1-91: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(propan-2-yl)pyridine-3-carboxamide;

[1328] 1-92: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(2,2,2-trifluoroethyl)pyridine-3-carboxamide;

[1329] 1-93: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-cyclohexyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1330] 1-94: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3-cyano-5-methoxyphenyl)pyridine-3-carboxamide;

[1331] 1-95: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide;

[1332] 1-96: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-N-[(1S)-1-cyclopropylethyl]pyridine-3-carboxamide;

[1333] 1-97: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1S)-1-phenylethyl]pyridine-3-carboxamide;

[1334] 1-98: 4-[(3S)-3-amino-3-(hydroxymethyl)pyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1335] 1-101: 4-[(3R,4R)-3-amino-4-fluoropyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1336] 1-103: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide;

[1337] 1-104: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1-methyl-1H-pyrazol-5-yl)methyl]pyridine-3-carboxamide;

[1338] 1-105: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1-methyl-1H-pyrazol-3-yl)methyl]pyridine-3-carboxamide;

[1339] 1-106: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1-methyl-1H-imidazol-2-yl)methyl]pyridine-3-carboxamide;

[1340] 1-107: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1-methyl-1H-pyrazol-4-yl)methyl]pyridine-3-carboxamide;

[1341] 1-108: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(pyrimidin-2-yl)methyl]pyridine-3-carboxamide;

[1342] 1-109: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(4-benzylpiperazine-1-carbonyl)-3-(3,5-difluorophenyl)pyridine-2-carbonitrile;

[1343] 1-110: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(3-phenylpropyl)pyridine-3-carboxamide;

[1344] 1-111: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(1-phenylpiperidin-4-yl)pyridine-3-carboxamide;

[1345] 1-112: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1346] 1-113: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(2,2-dimethyloxan-4-yl)pyridine-3-carboxamide;

[1347] 1-114: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1,2-oxazol-3-yl)methyl]pyridine-3-carboxamide;

[1348] 1-115: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2-hydroxyphenyl)methyl]pyridine-3-carboxamide;

[1349] 1-116: 4-[(3R)-3-amino-3-(methoxymethyl)pyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1350] 1-118: 4-[(3S)-3-amino-3-(2,2-difluoroethyl)pyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1351] 1-120: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-[3-(difluoromethoxy)phenyl]pyridine-3-carboxamide;

[1352] 1-122: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide;

[1353] 1-123: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide;

[1354] 1-124: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3-fluorophenyl)-6-methylpyridine-3-carboxamide;

[1355] 1-125: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide;

[1356] 1-126: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[1-(pyrimidin-2-yl)ethyl]pyridine-3-carboxamide;

[1357] 1-127: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-[3-(trifluoromethoxy)phenyl]pyridine-3-carboxamide;

[1358] 1-130: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;

[1359] 1-132: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[1-(1,2-oxazol-3-yl)ethyl]pyridine-3-carboxamide;

[1360] 1-133: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[1-(1-methyl-1H-1,2,3-triazol-4-yl)ethyl]pyridine-3-carboxamide;

[1361] 1-135: 4-[(3R,4R)-3-amino-4-fluoropyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1362] 1-137: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;

[1363] 1-138: 4-[(3R,4R)-3-amino-4-fluoropyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-cyano-N-[(1S)-1-cyclopropylethyl]pyridine-3-carboxamide;

[1364] 1-140: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1365] 1-141: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;

[1366] 1-143: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-[3-(difluoromethoxy)-5-fluorophenyl]pyridine-3-carboxamide;

[1367] 1-144: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;

[1368] 1-145: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-3,3-difluorocyclopentyl]-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;

[1369] 1-146: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide;

[1370] 1-147: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1371] 1-149: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-[3-(difluoromethoxy)phenyl]pyridine-3-carboxamide;

[1372] 1-150: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;

[1373] 1-151: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1374] 1-152: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;

[1375] 1-153: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methoxypyridine-3-carboxamide;

[1376] 1-154: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-6-methoxy-5-[3-(trifluoromethoxy)phenyl]pyridine-3-carboxamide;

[1377] 1-163: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(2,2-difluoro-2H-1,3-benzodioxol-4-yl)pyridine-3-carboxamide;

[1378] 1-164: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-[3-fluoro-5-(trifluoromethyl)phenyl]-6-methoxypyridine-3-carboxamide;

[1379] 1-165: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-[3-(difluoromethoxy)phenyl]-6-methoxypyridine-3-carboxamide;

[1380] 1-168: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-[3-(difluoromethoxy)phenyl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1381] 1-171: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1382] 1-172: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclobutyl)-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methylpyridine-3-carboxamide;

[1383] 1-173: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methylpyridine-3-carboxamide;

[1384] 1-174: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methylpyridine-3-carboxamide;

[1385] 1-175: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(2,2-difluoro-2H-1,3-benzodioxol-5-yl)pyridine-3-carboxamide;

[1386] 1-176: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-ethoxypyridine-3-carboxamide;

[1387] 1-177: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-6-(2,2-difluoroethoxy)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1388] 1-178: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-6-(cyclopropylmethoxy)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1389] 1-179: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-(2-methoxyethoxy)pyridine-3-carboxamide;

[1390] 1-180: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-[3-(difluoromethoxy)-5-fluorophenyl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1391] 1-181: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide;

[1392] 1-184: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(2,2-difluoro-2H-1,3-benzodioxol-4-yl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1393] 1-188: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1394] 1-189: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;

[1395] 1-190: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide;

[1396] 1-191: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyclopropyloxy-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1397] 1-192: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1398] 1-193: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-methoxy-N-[4-(trifluoromethyl)cyclohexyl]pyridine-3-carboxamide;

[1399] 1-194: 4-[(3S)-3-Aminopyrrolidin-1-yl]-N-(1-cyclopropyl-2,2,2-trifluoroethyl)-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;

[1400] 1-195: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-(trifluoromethyl)pyridine-3-carboxamide;

[1401] 1-196: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-6-methoxypyridine-3-carboxamide;

[1402] 1-197: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-N-[(1S)-1-cyclopropylethyl]-6-(trifluoromethyl)pyridine-3-carboxamide;

[1403] 1-198: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-(trifluoromethyl)pyridine-3-carboxamide;

[1404] 1-199: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;

[1405] 1-200: ethyl 2-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)acetate;

[1406] 1-201: ethyl 3-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)propanoate;

[1407] 1-202: ethyl 4-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)butanoate;

[1408] 1-203: 2-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)acetic acid

[1409] 1-204: 3-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)propanoic acid;

[1410] 1-205: 4-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)butanoic acid;

[1411] 1-209: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,4-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;

[1412] 1-210: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;

[1413] 1-211: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;

[1414] 1-212: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-(trifluoromethyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1415] 1-213: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-cyclohexyl-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;

[1416] 1-214: 4-[(3S)-3-Aminopyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;

[1417] 1-215: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-dichlorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;

[1418] 1-216: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-6-(trifluoromethyl)pyridine-3-carboxamide;

[1419] 1-217: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-6-(trifluoromethyl)pyridine-3-carboxamide;

[1420] 1-218: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-(cyclopropylmethyl)-5-(3,5-difluorophenyl)-N-methylpyridine-3-carboxamide;

[1421] 1-219: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-N-methylpyridine-3-carboxamide;

[1422] 1-222: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1423] 1-223: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(1-hydroxycyclopentyl)methyl]-6-methylpyridine-3-carboxamide;

[1424] 1-224: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(1-cyclopropyl-2-hydroxyethyl)-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide;

[1425] 1-225: 4-(3-aminopyrrolidin-1-yl)-6-cyano-5-(3,5-difluorophenyl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-carboxamide;

[1426] 1-226: 4-[(3S)-3-Aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-carboxamide;

[1427] 1-227: 4-[(3R)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1428] 1-228: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1429] 1-229: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methoxypyridine-3-carboxamide;

[1430] 1-230: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1431] 1-231: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1432] 1-232: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-[3-(difluoromethoxy)phenyl]-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1433] 1-233: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide;

[1434] 1-234: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-{3-fluorobicyclo[1.1.1]pentan-1-yl}pyridine-3-carboxamide;

[1435] 1-235: (3S)-1-[3-(3,5-difluorophenyl)-2-methoxy-5-(piperidine-1-carbonyl)pyridin-4-yl]pyrrolidin-3-amine;

[1436] 1-236: (3S)-1-[3-(3,5-difluorophenyl)-5-(4,4-difluoropiperidine-1-carbonyl)-2-methoxypyridin-4-yl]pyrrolidin-3-amine;

[1437] 1-237: (3S)-1-[3-(3,5-difluorophenyl)-5-(3,3-difluoropiperidine-1-carbonyl)-2-methoxypyridin-4-yl]pyrrolidin-3-amine;

[1438] 1-238: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methoxy-N-[(1,2-oxazol-3-yl)methyl]pyridine-3-carboxamide;

[1439] 1-239: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methoxy-N-[(1,2-oxazol-3-yl)methyl]pyridine-3-carboxamide;

[1440] 1-240: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methoxy-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide;

[1441] 1-241: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methoxy-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide;

[1442] 1-242: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methyl-N-[(1,2-oxazol-3-yl)methyl]pyridine-3-carboxamide;

[1443] 1-243: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methyl-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide;

[1444] 1-244: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-cyano-N-[(1,2-oxazol-3-yl)methyl]pyridine-3-carboxamide;

[1445] 1-245: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-cyano-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide;

[1446] 1-246: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-(2-hydroxyethoxy)pyridine-3-carboxamide;

[1447] 1-247: 2-({4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-{[(1S)-1-cyclopropylethyl]carbamoyl}-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)acetic acid;

[1448] 1-259: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,4-difluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1449] 1-260: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-chloro-3-fluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1450] 1-261: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-4-fluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1451] 1-262: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,4-difluorophenyl)-6-methoxypyridine-3-carboxamide;

[1452] 1-263: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-chloro-3-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methoxypyridine-3-carboxamide;

[1453] 1-264: 3-({4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-{[(1S)-1-cyclopropylethyl]carbamoyl}-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)propanoic acid;

[1454] 1-265: 4-({4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-{[(1S)-1-cyclopropylethyl]carbamoyl}-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)butanoic acid;

[1455] 1-266: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-[(oxetan-3-yl)methoxy]pyridine-3-carboxamide;

[1456] 1-267: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-(benzyloxy)-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1457] 1-268: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-N-(4,4-difluorocyclohexyl)-6-methylpyridine-3-carboxamide;

[1458] 1-269: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-N-(3,3-difluorocyclobutyl)-6-methylpyridine-3-carboxamide;

[1459] 1-272: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide;

[1460] 1-273: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-6-methoxypyridine-3-carboxamide;

[1461] 1-275: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1462] 1-276: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1463] 1-277: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-(4,4-difluorocyclohexyl)-6-methylpyridine-3-carboxamide;

[1464] 1-278: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-6-methylpyridine-3-carboxamide;

[1465] 1-279: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,4-difluorophenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1466] 1-280: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-N-[(1S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide;

[1467] 1-281: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyclopropyl-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;

[1468] 1-282: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methoxypyridine-3-carboxamide;

[1469] 1-283: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1470] 1-284: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-(4,4-difluorocyclohexyl)-6-methoxypyridine-3-carboxamide;

[1471] 1-285: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-(3,3-difluorocyclobutyl)-6-methoxypyridine-3-carboxamide;

[1472] 1-286: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-6-methoxypyridine-3-carboxamide;

[1473] 1-287: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-4-fluorophenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1474] 1-288: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,4-difluorophenyl)-6-methylpyridine-3-carboxamide;

[1475] 1-289: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-4-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide;

[1476] 1-290: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyclopropyl-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1477] 1-5: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2'-cyano-N-(3-methylphenyl)-[3,4'-bipyridine]-5-carboxamide;

[1478] 1-6: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,5-dimethylphenyl)-2'-methyl-[3,4'-bipyridine]-5-carboxamide;

[1479] 1-121: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(1-methyl-1H-pyrazol-3-yl)pyridine-3-carboxamide;

[1480] 1-128: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(2-methyl-1,3-thiazol-5-yl)pyridine-3-carboxamide;

[1481] 1-129: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-[(1S)-1-cyclopropylethyl]-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide;

[1482] 1-131: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2',6'-dimethyl-[3,4'-bipyridine]-5-carboxamide;

[1483] 1-134: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(1,2-oxazol-4-yl)pyridine-3-carboxamide;

[1484] 1-142: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5'-fluoro-[3,3'-bipyridine]-5-carboxamide;

[1485] 1-148: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-6-methyl-5-(1-methyl-1H-pyrazol-4-yl)pyridine-3-carboxamide;

[1486] 1-155: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-6-methyl-5-[1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]pyridine-3-carboxamide;

[1487] 1-156: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(1-cyclopropyl-1H-pyrazol-4-yl)-N-[(1S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide;

[1488] 1-157: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2'-methoxy-2-methyl-[3,4'-bipyridine]-5-carboxamide;

[1489] 1-158: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5'-chloro-N-[(1S)-1-cyclopropylethyl]-2-methyl-[3,3'-bipyridine]-5-carboxamide;

[1490] 1-159: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2-methyl-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide;

[1491] 1-160: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5'-fluoro-2-methyl-[3,3'-bipyridine]-5-carboxamide;

[1492] 1-166: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2-methoxy-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide;

[1493] 1-167: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5'-chloro-N-[(1S)-1-cyclopropylethyl]-2-methoxy-[3,3'-bipyridine]-5-carboxamide;

[1494] 1-169: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-2'-(trifluoromethyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]-[3,4'-bipyridine]-5-carboxamide;

[1495] 1-170: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-2'-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]-[3,4'-bipyridine]-5-carboxamide;

[1496] 1-185: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-methoxy-5-(2-methylpyrimidin-5-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1497] 1-187: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1498] 1-206: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2'-ethoxy-2-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide;

[1499] 1-208: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2'-methoxy-2-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide;

[1500] 1-248: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-cyclopentyl-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide;

[1501] 1-249: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-(pentan-3-yl)-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide;

[1502] 1-250: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-(2-methylpropyl)-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide;

[1503] 1-251: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-butyl-2-cyano-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide;

[1504] 1-252: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-cyclohexyl-2'-methoxy-[3,4'-bipyridine]-5-carboxamide;

[1505] 1-253: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-2'-methoxy-N-(pentan-3-yl)-[3,4'-bipyridine]-5-carboxamide;

[1506] 1-254: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-cyclopentyl-2'-methoxy-[3,4'-bipyridine]-5-carboxamide;

[1507] 1-255: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-2'-methoxy-2-methyl-[3,4'-bipyridine]-5-carboxamide;

[1508] 1-256: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopentyl-2'-methoxy-2-methyl-[3,4'-bipyridine]-5-carboxamide;

[1509] 1-257: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-2-methyl-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide;

[1510] 1-258: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopentyl-2-methyl-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide;

[1511] 1-270: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-2'-methoxy-N-(2-methylpropyl)-[3,4'-bipyridine]-5-carboxamide;

[1512] 2-1: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-ethyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[1513] 2-2: (3S)-3-methyl-1-[3-(4-methyl-1H-1,3-benzodiazol-2-yl)-5-(pyrrolidine-1-carbonyl)pyridin-4-yl]pyrrolidin-3-amine;

[1514] 2-3: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-ethyl-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[1515] 2-4: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopentyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[1516] 2-5: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-(oxolan-3-yl)pyridine-3-carboxamide;

[1517] 2-6: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-phenylpyridine-3-carboxamide;

[1518] 2-7: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-(2,2,2-trifluoroethyl)pyridine-3-carboxamide;

[1519] 2-8: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(2-methoxyethyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[1520] 2-9: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(2-hydroxyethyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[1521] 2-10: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-(2,2,2-trifluoroethyl)pyridine-3-carboxamide;

[1522] 2-11: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide;

[1523] 2-12: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopropyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[1524] 2-13: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(cyclopropylmethyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[1525] 2-14: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(1-cyclopropylethyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[1526] 2-15: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[1527] 2-16: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopentyl-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[1528] 2-17: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[1529] 2-18: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-[(2R)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide;

[1530] 2-19: (3S)-1-[3-(3,3-dimethylpyrrolidin-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine;

[1531] 2-20: (3S)-1-[3-(2,2-dimethylpyrrolidin-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine;

[1532] 2-21: (3S)-1-[3-(3,3-dimethylazetidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine;

[1533] 2-22: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopropyl-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[1534] 2-23: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(cyclopropylmethyl)-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[1535] 2-24: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-fluoro-1H-1,3-benzodiazol-2-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;

[1536] 2-25: (3S)-1-[3-(3,3-difluoropyrrolidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine;

[1537] 2-26: (3S)-1-(3-{2-azatricyclic[3.3.1.13, 7 ]decane-2-carbonyl}-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl)-3-methylpyrrolidin-3-amine;

[1538] 2-27: (3S)-1-[3-(3-tert-butylpyrrolidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine;

[1539] 2-28: (3S)-1-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl}-3-methylpyrrolidin-3-amine;

[1540] 2-29: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[1541] 2-30: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(7-fluoro-4-methyl-1H-1,3-benzodiazol-2-yl)-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide;

[1542] 2-31: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(cyclobutylmethyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[1543] 2-32: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-(4,4,4-trifluorobutan-2-yl)pyridine-3-carboxamide;

[1544] 2-33: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[2.2.1]heptan-1-yl}-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[1545] 2-34: (3S)-1-[3-(2,3-dihydro-1H-indole-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine;

[1546] 2-35: (3S)-1-(3-{2-azabicyclo[2.2.2]octane-2-carbonyl}-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl)-3-methylpyrrolidin-3-amine;

[1547] 2-36: (3S)-3-methyl-1-[3-(4-methyl-1H-1,3-benzodiazol-2-yl)-5-[2-(propan-2-yl)pyrrolidine-1-carbonyl]pyridin-4-yl]pyrrolidin-3-amine;

[1548] 2-37: (3S)-1-{3-[(3aR)-octahydrocyclopenta[b]pyrrole-1-carbonyl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl}-3-methylpyrrolidin-3-amine;

[1549] 2-38: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;

[1550] 2-39: (3S)-1-(3-{5-azaspiro[2.4]heptane-5-carbonyl}-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl)-3-methylpyrrolidin-3-amine;

[1551] 2-40: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-[(2S)-1,1,1-trifluorobutan-2-yl]pyridine-3-carboxamide;

[1552] 2-41: (3S)-3-methyl-1-[3-(4-methyl-1H-1,3-benzodiazol-2-yl)-5-[(2S)-2-(trifluoromethyl)pyrrolidine-1-carbonyl]pyridin-4-yl]pyrrolidin-3-amine;

[1553] 2-42: (3S)-1-[3-(3-cyclopropylpyrrolidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridi...

Claims

1. A compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof: in: Ring A is a carbocyclic ring or a heterocyclic ring; X is N or C–R a ; Y is N or C–R b ; Z is N or C–R c ; R a , R b and R c are independently hydrogen, halogen, –CN, –N(R 9 2. –OR f , –CO2R 9 、–C(=O)N(R 9 )2, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 fluoroalkoxy, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted monocyclic carbocycle, or substituted or unsubstituted monocyclic heterocycle; R f For -L 1 -R g ; L 1 is absent, C1-C6 alkylene, C1-C6 fluoroalkylene, or C1-C6 heteroalkylene; R g is hydrogen, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, -CO2R 9 , or -C(=O)N(R 9 )2, substituted or unsubstituted monocyclic heterocycle; R 1 and R 2 are independently hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C6 cycloalkyl, or substituted or unsubstituted C3-C5 heterocycloalkyl; R 3 For hydrogen, -CN, –CO2R 9 、–C(=O)N(R 9 )2, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl; R 4 and R 5 are independently hydrogen, halogen, –OR 9 , –N(R 9 )2, –CN, –CO2R 9 、–C(=O)N(R 9 )2, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 fluoroalkoxy, or substituted or unsubstituted C1-C6 heteroalkyl; R 6 is substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C1-C8 fluoroalkyl, substituted or unsubstituted C1-C8 heteroalkyl, or -L 2 -R 6a ; L 2 is absent, substituted or unsubstituted C1-C8 alkylene, or -CHR 6b -; R 6a is substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted C2-C 10 Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl; R 6b is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, or substituted or unsubstituted C3-C6 cycloalkyl; R 7 is hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted C2-C 10 Heterocycloalkyl, or substituted or unsubstituted C1-C9 heteroaryl; or R 6 and R 7 together with the nitrogen to which they are attached, form a substituted or unsubstituted N-containing heterocyclic ring; Each R 8 , R 11 and R 12 are independently hydrogen, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted monocyclic carbocycle, substituted or unsubstituted monocyclic heterocycle, -CN, -OR 9 , –C(=O)R 10 , –CO2R 9 、–C(=O)N(R 9 )2. –N(R 9 )2. –NR 9 C(=O)R 10 ,–NR 9 C(=O)OR 10 ,–NR 9 C(=O)N(R 9 )2. –C(R 9 )=N-OR 9 ,–SR 9 , –S(=O)R 9 , –SO2R 9 , or –SO2N(R 9 )2; or R 11 With adjacent R 8 And the R 11 and the adjacent R 8 The atoms joined together form a fused substituted or unsubstituted carbocyclic ring, or a fused substituted or unsubstituted heterocyclic ring; Each R 9 are independently hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted monocyclic heteroaryl; or two R on the same N atom 9 together with the N atom to which they are attached, form a substituted or unsubstituted N-containing heterocyclic ring; Each R 10 are independently substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted monocyclic heteroaryl; and n is 0-3.

2. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein: R 1 is hydrogen; R 2 is H or C1-C6 alkyl; R 3 is hydrogen, C1-C6 alkyl or C1-C6 fluoroalkyl; and R 4 and R 5 Each is independently hydrogen, halogen, C1-C6 alkyl, or C1-C6 fluoroalkyl.

3. The compound according to claim 2, or a pharmaceutically acceptable salt or solvate thereof, wherein: R 1 and R 2 Each is hydrogen; R 3 is hydrogen or -CH3; and R 4 and R 5 Each is hydrogen.

4. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has a structure of formula (Ia) or (Ib) or a pharmaceutically acceptable salt or solvate thereof:

5. The compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt or solvate thereof, wherein: X is C–R a ; Y is N; and Z is C–R c ;or X is CH; Y is N; and Z is C–R c ;or X is C–R a ; Y is N; and Z is CH; or X is N; Y is C–R b ; and Z is C–R c ;or X is C–R a ; Y is C–R b ; and Z is N; or X is N; Y is N; and Z is C–R c ;or X is C–R a ; Y is N; and Z is N.

6. The compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has a structure of formula (IIa) or a pharmaceutically acceptable salt or solvate thereof:

7. The compound according to claim 6, or a pharmaceutically acceptable salt or solvate thereof, wherein: Ring A is phenyl, monocyclic heteroaryl or bicyclic heteroaryl.

8. A compound selected from: 1-1: 4-[(3S)-3-aminopyrrolidin-1-yl]-N,5-bis(3,5-dimethylphenyl)pyridine-3-carboxamide; 1-3: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-(3-chloro-5-fluorophenyl)-5-(3,5-dimethylphenyl)pyridine-3-carboxamide; 1-4: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-4-fluorophenyl)-N-(2-fluorophenyl)pyridine-3-carboxamide; 1-7: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-cyanophenyl)-N-cyclohexylpyridine-3-carboxamide; 1-8: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-cyanophenyl)-N-(1-methylcyclobutyl)pyridine-3-carboxamide; 1-9: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-benzyl-5-(3-cyanophenyl)pyridine-3-carboxamide; 1-10: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyanophenyl)-N-(4,4-difluorocyclohexyl)pyridine-3-carboxamide; 1-11: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-dimethylcyclohexyl)-5-(3,5-dimethylphenyl)pyridine-3-carboxamide; 1-12: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-dimethylphenyl)pyridine-3-carboxamide; 1-13: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide; 1-14: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclohexyl)-5-(3,5-dimethylphenyl)pyridine-3-carboxamide; 1-15: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-fluoro-5-methylphenyl)-N-[1-(trifluoromethyl)cyclopentyl]pyridine-3-carboxamide; 1-16: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-17: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(2,3-dihydro-1H-inden-1-yl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide; 1-18: N-(adamantan-2-yl)-4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide; 1-19: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(1-ethylcyclobutyl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide; 1-20: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,4,5-trifluorophenyl)pyridine-3-carboxamide; 1-21: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-22: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(3,3-dimethylcyclobutyl)pyridine-3-carboxamide; 1-23: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopropyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-24: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(1-cyclopropylethyl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide; 1-25: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(dicyclopropylmethyl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide; 1-26: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(cyclopropylmethyl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide; 1-27: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-fluoro-5-methylphenyl)-N-(1-methyl-1H-pyrazol-3-yl)pyridine-3-carboxamide; 1-28: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2,2,2-trifluoroethyl)pyridine-3-carboxamide; 1-29: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-tert-butyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-30: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-31: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(pentan-3-yl)pyridine-3-carboxamide; 1-32: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(1-methylcyclopropyl)methyl]pyridine-3-carboxamide; 1-33: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(cyclobutylmethyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-34: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(1-methylcyclobutyl)pyridine-3-carboxamide; 1-35: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-(3,3-difluorocyclobutyl)pyridine-3-carboxamide; 1-37: 4-[(3R,4R)-3-amino-4-fluoropyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-38: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(3-methylbutan-2-yl)pyridine-3-carboxamide; 1-39: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2,4-dimethylpentan-3-yl)pyridine-3-carboxamide; 1-40: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(2-cyclopropylpropan-2-yl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-41: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-42: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(2,2-difluorocyclopropyl)methyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-43: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(2,2-dimethylcyclopropyl)methyl]pyridine-3-carboxamide; 1-44: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1R)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-45: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(1,1,1-trifluoro-3-methylbutan-2-yl)pyridine-3-carboxamide; 1-46: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2-methylpropyl)pyridine-3-carboxamide; 1-47: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(1-fluorocyclobutyl)methyl]pyridine-3-carboxamide; 1-48: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-49: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-50: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(3,3-difluorocyclobutyl)methyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-51: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(dicyclopropylmethyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-52: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[trans-2-fluorocyclohexyl]pyridine-3-carboxamide; 1-53: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(2R)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-54: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-55: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(trans-3-fluorocyclobutyl]pyridine-3-carboxamide; 1-56: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(1-cyclobutyl-2,2,2-trifluoroethyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-57: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2-methylbutyl)pyridine-3-carboxamide; 1-58: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2-ethylbutyl)pyridine-3-carboxamide; 1-59: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[cis-3-fluorocyclobutyl]pyridine-3-carboxamide; 1-60: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(4,4,4-trifluorobutan-2-yl)pyridine-3-carboxamide; 1-61: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-(dicyclopropylmethyl)pyridine-3-carboxamide; 1-62: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2,2-difluoropropyl)pyridine-3-carboxamide; 1-64: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-65: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3-fluorophenyl)pyridine-3-carboxamide; 1-66: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,4-difluorophenyl)pyridine-3-carboxamide; 1-67: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-68: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-69: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-70: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-N-(dicyclopropylmethyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-71: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-72: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(pentan-3-yl)pyridine-3-carboxamide; 1-73: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-N-cycloheptyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-74: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide; 1-76: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(pentan-3-yl)pyridine-3-carboxamide; 1-77: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-78: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-cyclopentyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-79: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-80: 4-[(3S)-3-aminopyrrolidin-1-yl]-3-(3,5-difluorophenyl)-5-(piperidine-1-carbonyl)pyridine-2-carbonitrile; 1-81: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-N-cyclohexyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-82: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-N-cyclopentyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-83: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[cis-2-fluorocyclohexyl]pyridine-3-carboxamide; 1-84: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3-chlorophenyl)-6-cyanopyridine-3-carboxamide; 1-85: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(2-methylpropyl)pyridine-3-carboxamide; 1-86: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-(cyclopropylmethyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-87: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-cyclobutyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-88: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(oxan-4-yl)pyridine-3-carboxamide; 1-89: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(oxan-3-yl)pyridine-3-carboxamide; 1-90: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3-chloro-5-fluorophenyl)-6-cyanopyridine-3-carboxamide; 1-91: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(propan-2-yl)pyridine-3-carboxamide; 1-92: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(2,2,2-trifluoroethyl)pyridine-3-carboxamide; 1-93: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-cyclohexyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-94: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3-cyano-5-methoxyphenyl)pyridine-3-carboxamide; 1-95: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide; 1-96: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-N-[(1S)-1-cyclopropylethyl]pyridine-3-carboxamide; 1-97: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1S)-1-phenylethyl]pyridine-3-carboxamide; 1-98: 4-[(3S)-3-amino-3-(hydroxymethyl)pyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-101: 4-[(3R,4R)-3-amino-4-fluoropyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-103: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide; 1-104: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1-methyl-1H-pyrazol-5-yl)methyl]pyridine-3-carboxamide; 1-105: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1-methyl-1H-pyrazol-3-yl)methyl]pyridine-3-carboxamide; 1-106: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1-methyl-1H-imidazol-2-yl)methyl]pyridine-3-carboxamide; 1-107: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1-methyl-1H-pyrazol-4-yl)methyl]pyridine-3-carboxamide; 1-108: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(pyrimidin-2-yl)methyl]pyridine-3-carboxamide; 1-109: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(4-benzylpiperazine-1-carbonyl)-3-(3,5-difluorophenyl)pyridine-2-carbonitrile; 1-110: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(3-phenylpropyl)pyridine-3-carboxamide; 1-111: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(1-phenylpiperidin-4-yl)pyridine-3-carboxamide; 1-112: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-113: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(2,2-dimethyloxan-4-yl)pyridine-3-carboxamide; 1-114: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1,2-oxazol-3-yl)methyl]pyridine-3-carboxamide; 1-115: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2-hydroxyphenyl)methyl]pyridine-3-carboxamide; 1-116: 4-[(3R)-3-amino-3-(methoxymethyl)pyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-118: 4-[(3S)-3-amino-3-(2,2-difluoroethyl)pyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-120: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-[3-(difluoromethoxy)phenyl]pyridine-3-carboxamide; 1-122: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide; 1-123: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide; 1-124: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3-fluorophenyl)-6-methylpyridine-3-carboxamide; 1-125: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide; 1-126: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[1-(pyrimidin-2-yl)ethyl]pyridine-3-carboxamide; 1-127: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-[3-(trifluoromethoxy)phenyl]pyridine-3-carboxamide; 1-130: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide; 1-132: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[1-(1,2-oxazol-3-yl)ethyl]pyridine-3-carboxamide; 1-133: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[1-(1-methyl-1H-1,2,3-triazol-4-yl)ethyl]pyridine-3-carboxamide; 1-135: 4-[(3R,4R)-3-amino-4-fluoropyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-137: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide; 1-138: 4-[(3R,4R)-3-amino-4-fluoropyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-cyano-N-[(1S)-1-cyclopropylethyl]pyridine-3-carboxamide; 1-140: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-141: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide; 1-143: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-[3-(difluoromethoxy)-5-fluorophenyl]pyridine-3-carboxamide; 1-144: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide; 1-145: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-3,3-difluorocyclopentyl]-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide; 1-146: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide; 1-147: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-149: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-[3-(difluoromethoxy)phenyl]pyridine-3-carboxamide; 1-150: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide; 1-151: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-152: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide; 1-153: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methoxypyridine-3-carboxamide; 1-154: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-6-methoxy-5-[3-(trifluoromethoxy)phenyl]pyridine-3-carboxamide; 1-163: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(2,2-difluoro-2H-1,3-benzodioxol-4-yl)pyridine-3-carboxamide; 1-164: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-[3-fluoro-5-(trifluoromethyl)phenyl]-6-methoxypyridine-3-carboxamide; 1-165: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-[3-(difluoromethoxy)phenyl]-6-methoxypyridine-3-carboxamide; 1-168: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-[3-(difluoromethoxy)phenyl]-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-171: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methyl-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-172: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclobutyl)-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methylpyridine-3-carboxamide; 1-173: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methylpyridine-3-carboxamide; 1-174: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methylpyridine-3-carboxamide; 1-175: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(2,2-difluoro-2H-1,3-benzodioxol-5-yl)pyridine-3-carboxamide; 1-176: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-ethoxypyridine-3-carboxamide; 1-177: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-6-(2,2-difluoroethoxy)-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-178: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-6-(cyclopropylmethoxy)-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-179: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-(2-methoxyethoxy)pyridine-3-carboxamide; 1-180: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-[3-(difluoromethoxy)-5-fluorophenyl]-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-181: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide; 1-184: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(2,2-difluoro-2H-1,3-benzodioxol-4-yl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-188: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methoxy-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-189: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide; 1-190: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide; 1-191: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyclopropyloxy-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-192: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide; 1-193: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-methoxy-N-[4-(trifluoromethyl)cyclohexyl]pyridine-3-carboxamide; 1-194: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-(1-cyclopropyl-2,2,2-trifluoroethyl)-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide; 1-195: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-(trifluoromethyl)pyridine-3-carboxamide; 1-196: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-{3-fluorobicyclo[ 1.1.1]pentan-1-yl}-6-methoxypyridine-3-carboxamide; 1-197: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-N-[(1S)-1-cyclopropylethyl]-6-(trifluoromethyl)pyridine-3-carboxamide; 1-198: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-(trifluoromethyl)pyridine-3-carboxamide; 1-199: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide; 1-200: ethyl 2-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)acetate; 1-201: ethyl 3-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)propanoate; 1-202: ethyl 4-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)butanoate; 1-203: 2-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)acetic acid 1-204: 3-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)propanoic acid; 1-205: 4-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)butanoic acid; 1-209: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,4-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide; 1-210: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide; 1-211: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide; 1-212: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-(trifluoromethyl)-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-213: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-cyclohexyl-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide; 1-214: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide; 1-215: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-dichlorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide; 1-216: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-{3-fluorobicyclo[ 1.1.1]pentan-1-yl}-6-(trifluoromethyl)pyridine-3-carboxamide; 1-217: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-{3-fluorobicyclo[ 1.1.1]pentan-1-yl}-6-(trifluoromethyl)pyridine-3-carboxamide; 1-218: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-(cyclopropylmethyl)-5-(3,5-difluorophenyl)-N-methylpyridine-3-carboxamide; 1-219: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-N-methylpyridine-3-carboxamide; 1-222: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide; 1-223: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(1-hydroxycyclopentyl)methyl]-6-methylpyridine-3-carboxamide; 1-224: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(1-cyclopropyl-2-hydroxyethyl)-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide; 1-225: 4-(3-aminopyrrolidin-1-yl)-6-cyano-5-(3,5-difluorophenyl)-N-(1,1,1-trifluoropropane-2-yl)pyridine-3-carboxamide; 1-226: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-carboxamide; 1-227: 4-[(3R)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2R)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-228: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-229: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methoxypyridine-3-carboxamide; 1-230: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-231: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methyl-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-232: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-[3-(difluoromethoxy)phenyl]-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide; 1-233: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide; 1-234: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-{3-fluorobicyclo[ 1.1.1]pentan-1-yl}pyridine-3-carboxamide; 1-235: (3S)-1-[3-(3,5-difluorophenyl)-2-methoxy-5-(piperidine-1-carbonyl)pyridin-4-yl]pyrrolidin-3-amine; 1-236: (3S)-1-[3-(3,5-difluorophenyl)-5-(4,4-difluoropiperidine-1-carbonyl)-2-methoxypyridin-4-yl]pyrrolidin-3-amine; 1-237: (3S)-1-[3-(3,5-difluorophenyl)-5-(3,3-difluoropiperidine-1-carbonyl)-2-methoxypyridin-4-yl]pyrrolidin-3-amine; 1-238: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methoxy-N-[(1,2-oxazol-3-yl)methyl]pyridine-3-carboxamide; 1-239: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methoxy-N-[(1,2-oxazol-3-yl)methyl]pyridine-3-carboxamide; 1-240: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methoxy-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide; 1-241: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methoxy-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide; 1-242: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methyl-N-[(1,2-oxazol-3-yl)methyl]pyridine-3-carboxamide; 1-243: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methyl-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide; 1-244: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-cyano-N-[(1,2-oxazol-3-yl)methyl]pyridine-3-carboxamide; 1-245: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-cyano-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide; 1-246: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-(2-hydroxyethoxy)pyridine-3-carboxamide; 1-247: 2-({4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-{[(1S)-1-cyclopropylethyl]carbamoyl}-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)acetic acid; 1-259: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,4-difluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-260: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-chloro-3-fluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-261: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-4-fluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide; 1-262: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,4-difluorophenyl)-6-methoxypyridine-3-carboxamide; 1-263: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-chloro-3-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methoxypyridine-3-carboxamide; 1-264: 3-({4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-{[(1S)-1-cyclopropylethyl]carbamoyl}-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)propanoic acid; 1-265: 4-({4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-{[(1S)-1-cyclopropylethyl]carbamoyl}-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)butanoic acid; 1-266: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-[(oxetan-3-yl)methoxy]pyridine-3-carboxamide; 1-267: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-(benzyloxy)-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-268: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-N-(4,4-difluorocyclohexyl)-6-methylpyridine-3-carboxamide; 1-269: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-N-(3,3-difluorocyclobutyl)-6-methylpyridine-3-carboxamide; 1-272: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide; 1-273: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-{3-fluorobicyclo[ 1.1.1]pentan-1-yl}-6-methoxypyridine-3-carboxamide; 1-275: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide; 1-276: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-277: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-(4,4-difluorocyclohexyl)-6-methylpyridine-3-carboxamide; 1-278: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-{3-fluorobicyclo[ 1.1.1]pentan-1-yl}-6-methylpyridine-3-carboxamide; 1-279: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,4-difluorophenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-280: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-N-[(1S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide; 1-281: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyclopropyl-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-282: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methoxypyridine-3-carboxamide; 1-283: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide; 1-284: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-(4,4-difluorocyclohexyl)-6-methoxypyridine-3-carboxamide; 1-285: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-(3,3-difluorocyclobutyl)-6-methoxypyridine-3-carboxamide; 1-286: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-{3-fluorobicyclo[ 1.1.1]pentan-1-yl}-6-methoxypyridine-3-carboxamide; 1-287: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-4-fluorophenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide; 1-288: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,4-difluorophenyl)-6-methylpyridine-3-carboxamide; 1-289: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-4-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide; 1-290: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyclopropyl-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-5: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2'-cyano-N-(3-methylphenyl)-[3,4'-bipyridine]-5-carboxamide; 1-6: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,5-dimethylphenyl)-2'-methyl-[3,4'-bipyridine]-5-carboxamide; 1-121: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(1-methyl-1H-pyrazol-3-yl)pyridine-3-carboxamide; 1-128: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(2-methyl-1,3-thiazol-5-yl)pyridine-3-carboxamide; 1-129: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-[(1S)-1-cyclopropylethyl]-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide; 1-131: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2',6'-dimethyl-[3,4'-bipyridine]-5-carboxamide; 1-134: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(1,2-oxazol-4-yl)pyridine-3-carboxamide; 1-142: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5'-fluoro-[3,3'-bipyridine]-5-carboxamide; 1-148: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-6-methyl-5-(1-methyl-1H-pyrazol-4-yl)pyridine-3-carboxamide; 1-155: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-6-methyl-5-[1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]pyridine-3-carboxamide; 1-156: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(1-cyclopropyl-1H-pyrazol-4-yl)-N-[(1S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide; 1-157: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2'-methoxy-2-methyl-[3,4'-bipyridine]-5-carboxamide; 1-158: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5'-chloro-N-[(1S)-1-cyclopropylethyl]-2-methyl-[3,3'-bipyridine]-5-carboxamide; 1-159: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2-methyl-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide; 1-160: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5'-fluoro-2-methyl-[3,3'-bipyridine]-5-carboxamide; 1-166: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2-methoxy-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide; 1-167: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5'-chloro-N-[(1S)-1-cyclopropylethyl]-2-methoxy-[3,3'-bipyridine]-5-carboxamide; 1-169: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-2'-(trifluoromethyl)-N-[(2S)-1,1,1-trifluoropropane-2-yl]-[3,4'-bipyridine]-5-carboxamide; 1-170: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-2'-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]-[3,4'-bipyridine]-5-carboxamide; 1-185: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-methoxy-5-(2-methylpyrimidin-5-yl)-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-187: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-206: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2'-ethoxy-2-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide; 1-208: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2'-methoxy-2-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide; 1-248: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-cyclopentyl-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide; 1-249: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-(pentan-3-yl)-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide; 1-250: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-(2-methylpropyl)-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide; 1-251: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-butyl-2-cyano-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide; 1-252: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-cyclohexyl-2'-methoxy-[3,4'-bipyridine]-5-carboxamide; 1-253: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-2'-methoxy-N-(pentan-3-yl)-[3,4'-bipyridine]-5-carboxamide; 1-254: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-cyclopentyl-2'-methoxy-[3,4'-bipyridine]-5-carboxamide; 1-255: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-2'-methoxy-2-methyl-[3,4'-bipyridine]-5-carboxamide; 1-256: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopentyl-2'-methoxy-2-methyl-[3,4'-bipyridine]-5-carboxamide; 1-257: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-2-methyl-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide; 1-258: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopentyl-2-methyl-2'-(trifluoromethyl)-[3,4'-bipyridine]-5-carboxamide; 1-270: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-2'-methoxy-N-(2-methylpropyl)-[3,4'-bipyridine]-5-carboxamide; 2-1: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-ethyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide; 2-2: (3S)-3-methyl-1-[3-(4-methyl-1H-1,3-benzodiazol-2-yl)-5-(pyrrolidine-1-carbonyl)pyridin-4-yl]pyrrolidin-3-amine; 2-3: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-ethyl-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide; 2-4: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopentyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide; 2-5: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-(oxolan-3-yl)pyridine-3-carboxamide; 2-6: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-phenylpyridine-3-carboxamide; 2-7: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-(2,2,2-trifluoroethyl)pyridine-3-carboxamide; 2-8: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(2-methoxyethyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide; 2-9: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(2-hydroxyethyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide; 2-10: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-(2,2,2-trifluoroethyl)pyridine-3-carboxamide; 2-11: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 2-12: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopropyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide; 2-13: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(cyclopropylmethyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide; 2-14: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(1-cyclopropylethyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide; 2-15: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide; 2-16: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopentyl-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide; 2-17: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide; 2-18: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-[(2R)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 2-19: (3S)-1-[3-(3,3-dimethylpyrrolidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine; 2-20: (3S)-1-[3-(2,2-dimethylpyrrolidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine; 2-21: (3S)-1-[3-(3,3-dimethylazetidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine; 2-22: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopropyl-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide; 2-23: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(cyclopropylmethyl)-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide; 2-24: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-fluoro-1H-1,3-benzodiazol-2-yl)-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 2-25: (3S)-1-[3-(3,3-difluoropyrrolidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine; 2-26: (3S)-1-(3-{2-azatricyclo[3.3.1.13, 7 ]decane-2-carbonyl}-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl)-3-methylpyrrolidin-3-amine; 2-27: (3S)-1-[3-(3-tert-butylpyrrolidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine; 2-28: (3S)-1-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl}-3-methylpyrrolidin-3-amine; 2-29: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide; 2-30: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(7-fluoro-4-methyl-1H-1,3-benzodiazol-2-yl)-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 2-31: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(cyclobutylmethyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide; 2-32: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-(4,4,4-trifluorobutan-2-yl)pyridine-3-carboxamide; 2-33: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[2.2.1]heptane-1-yl}-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide; 2-34: (3S)-1-[3-(2,3-dihydro-1H-indole-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine; 2-35: (3S)-1-(3-{2-azabicyclo[2.2.2]octane-2-carbonyl}-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl)-3-methylpyrrolidin-3-amine; 2-36: (3S)-3-methyl-1-[3-(4-methyl-1H-1,3-benzodiazol-2-yl)-5-[2-(propan-2-yl)pyrrolidine-1-carbonyl]pyridin-4-yl]pyrrolidin-3-amine; 2-37: (3S)-1-{3-[(3aR)-octahydrocyclopenta[b]pyrrole-1-carbonyl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl}-3-methylpyrrolidin-3-amine; 2-38: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide; 2-39: (3S)-1-(3-{5-azaspiro[2.4]heptane-5-carbonyl}-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl)-3-methylpyrrolidin-3-amine; 2-40: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-[(2S)-1,1,1-trifluorobutan-2-yl]pyridine-3-carboxamide; 2-41: (3S)-3-methyl-1-[3-(4-methyl-1H-1,3-benzodiazol-2-yl)-5-[(2S)-2-(trifluoromethyl)pyrrolidine-1-carbonyl]pyridin-4-yl]pyrrolidin-3-amine; 2-42: (3S)-1-[3-(3-cyclopropylpyrrolidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine; 2-43: (3S)-1-[3-(2-cyclopropylpyrrolidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine; 2-44: (3S)-3-methyl-1-[3-(4-methyl-1H-1,3-benzodiazol-2-yl)-5-[3-(trifluoromethyl)pyrrolidine-1-carbonyl]pyridin-4-yl]pyrrolidin-3-amine; 2-45: (3S)-1-(3-{2-azatricyclo[3.3.1.13, 7 ]decane-2-carbonyl}-5-(7-chloro-1H-1,3-benzodiazol-2-yl)pyridin-4-yl)-3-methylpyrrolidin-3-amine; 1-161: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(1-methyl-1H-indazol-6-yl)pyridine-3-carboxamide; 1-162: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(1-methyl-1H-indazol-4-yl)pyridine-3-carboxamide; 1-182: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-methoxy-5-(1-methyl-1H-1,3-benzodiazol-6-yl)-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-183: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-methoxy-5-(1-methyl-1H-indazol-4-yl)-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-186: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(2,1,3-benzoxadiazol-5-yl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropane-2-yl]pyridine-3-carboxamide; 1-2: 4-[(3R)-3-aminopyrrolidin-1-yl]-N,5-bis(3,5-dimethylphenyl)pyridine-3-carboxamide; 1-36: 4-[3-amino-3-(methoxymethyl)pyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-63: 4-[3-(1-aminoethyl)azetidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-75: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyanopyridine-3-carboxamide; 1-99: 4-[(3R)-3-amino-3-(hydroxymethyl)pyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-100: 4-[3-(1-aminoethyl)azetidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-102: 4-[(3S,4S)-3-amino-4-fluoropyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-117: 4-[(3S)-3-amino-3-(methoxymethyl)pyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-119: 4-[(3R)-3-amino-3-(2,2-difluoroethyl)pyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-136: 4-[(3S,4S)-3-amino-4-fluoropyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-139: 4-[(3S,4S)-3-amino-4-fluoropyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-cyano-N-[(1S)-1-cyclopropylethyl]pyridine-3-carboxamide; 1-220: 4-[(3S)-3-amino-3-(fluoromethyl)pyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-221: 4-[(3R)-3-amino-3-(fluoromethyl)pyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide; 1-274: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-bromo-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide; 3-1: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2-(3,5-difluorophenyl)pyridine-4-carboxamide; 3-2: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-2-(3,5-difluorophenyl)pyridine-4-carboxamide; 3-3: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-(3,5-difluorophenyl)-N-[(1S)-1-phenylethyl]pyridine-4-carboxamide; 3-4: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(dicyclopropylmethyl)-2-(3,5-difluorophenyl)pyridine-4-carboxamide; 3-5: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[2.2.1]heptane-1-yl}-2-(3,5-difluorophenyl)pyridine-4-carboxamide; 3-6: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cycloheptyl-2-(3,5-difluorophenyl)pyridine-4-carboxamide; 3-7: N-(adamantan-1-yl)-3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-(3,5-difluorophenyl)pyridine-4-carboxamide; 3-8: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopentyl-2-(3,5-difluorophenyl)pyridine-4-carboxamide; 4-1: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-chloro-N-[(1S)-1-cyclopropylethyl]-4-(3,5-difluorophenyl)pyridine-2-carboxamide; 4-2: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-4-(3,5-difluorophenyl)-5-methylpyridine-2-carboxamide; 4-3: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-cyano-N-[(1S)-1-cyclopropylethyl]-4-(3,5-difluorophenyl)pyridine-2-carboxamide; 4-4: 5-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-{[(1S)-1-cyclopropylethyl]carbamoyl}-4-(3,5-difluorophenyl)pyridine-3-carboxylic acid methyl ester; and 4-5: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N2-[(1S)-1-cyclopropylethyl]-4-(3,5-difluorophenyl)pyridine-2,5-dicarboxamide; or a pharmaceutically acceptable salt or solvate thereof.

9. A pharmaceutical composition comprising a compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient.

10. A method of treating a disease or condition in a mammal that would benefit from modulation of somatostatin receptor subtype 5 (SSTR5) activity, comprising administering to the mammal in need thereof a compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt or solvate thereof.

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