Heterocyclic compounds

Abstract

The present invention relates to a compound represented by general formula (I), 1 ~R 7 The present invention provides novel heterocyclic compounds having the formula:

Description

[Technical Field]

[0001] Field of Invention The present invention relates to organic compounds useful for the treatment or prevention of mammals, and more particularly to monoacylglycerol lipase (MAGL) inhibitors for the treatment or prevention of neuroinflammation, neurodegenerative diseases, pain, cancer, mental disorders, multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, anxiety disorders, migraines, depression, inflammatory bowel disease, abdominal pain, abdominal pain associated with irritable bowel syndrome, and / or visceral pain in mammals. [Background technology]

[0002] Background of the Invention Endocannabinoids (ECs) are signaling lipids that exert biological effects by interacting with cannabinoid receptors (CBRs) CB1 and CB2. They regulate several physiological processes, including neuroinflammation, neurodegeneration, and tissue regeneration (Iannotti, FA, et al., Progress in lipid research 2016, 62, 107-28). In the brain, the main endocannabinoid, 2-arachidonoylglycerol (2-AG), is produced by diacidglycerol lipase (DAGL) and hydrolyzed by monoacylglycerol lipase MAGL. MAGL hydrolyzes 85% of 2-AG, and the remaining 15% is hydrolyzed by ABHD6 and ABDH12 (Nomura, DK, et al., Science 2011, 334, 809). MAGL is expressed throughout the brain, as well as in most brain cell types, including neurons, astrocytes, oligodendrocytes, and microglia (Chanda, PK, et al., Molecular pharmacology 2010, 78, 996; Viader, A., et al., Cell reports 2015, 12, 798). Hydrolysis of 2-AG leads to the formation of arachidonic acid (AA), a precursor of prostaglandins (PG) and leukotrienes (LT). Oxidative metabolism of AA is increased in inflammatory tissues. Two major enzymatic pathways involved in the oxidation of arachidonic acid in the inflammatory process are cyclooxygenase, which produces PG, and 5-lipoxygenase, which produces LT. Among the various cyclooxygenase products formed during inflammation, PGE2 is one of the most important. These products have been detected at inflammatory sites, for example in the cerebrospinal fluid of patients with neurodegenerative disorders, and are thought to contribute to the inflammatory response and disease progression. Mice lacking MAGL (Mgll- / -) showed a dramatic decrease in 2-AG hydrolase activity and a dramatic increase in 2-AG levels in the nervous system, while other arachidonoyl-containing phospholipids and neutral lipid species, including anandamide (AEA), and other free fatty acids remained unchanged.Conversely, levels of AA and AA-derived prostaglandins, as well as other eicosanoids including prostaglandins E2 (PGE2), D2 (PGD2), and F2 (PGF2), and thromboxane B2 (TXB2), are significantly reduced. While the phospholipase A2 (PLA2) enzyme has been considered a major source of AA, cPLA2-deficient mice do not alter AA levels in their brains, highlighting the importance of the role of MAGL in the brain in regulating AA production and brain inflammatory processes.

[0003] Neuroinflammation is a common pathological alteration in brain diseases, including, but not limited to, neurodegenerative diseases (e.g., multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, and mental disorders such as anxiety and migraines). In the brain, the production of eicosanoids and prostaglandins regulates neuroinflammatory processes. The pro-inflammatory substance lipopolysaccharide (LPS) results in a robust, time-dependent increase in brain eicosanoids, which is markedly blunted in Mgll- / - mice. LPS treatment also induces widespread elevations of inflammatory cytokines, including interleukin-1-α (IL-1-α), IL-1β, IL-6, and tumor necrosis factor-α (TNF-α), which are suppressed in Mgll- / - mice.

[0004] Neuroinflammation is characterized by the activation of innate immune cells in the central nervous system, microglia, and astrocytes. Anti-inflammatory drugs have been reported to suppress glial cell activation and disease progression, including Alzheimer's disease and multiple sclerosis, in preclinical models (Lleo A., Cell Mol Life Sci. 2007, 64, 1403). Importantly, genetic and / or pharmacological disruption of MAGL activity also inhibits LPS-induced activation of microglial cells in the brain (Nomura, DK, et al., Science 2011, 334, 809).

[0005] Furthermore, genetic and / or pharmacological disruption of MAGL activity has been shown to be protective in several animal models of neurodegeneration, including, but not limited to, Alzheimer's disease, Parkinson's disease, and multiple sclerosis. For example, irreversible MAGL inhibitors are widely used in preclinical models of neuroinflammation and neurodegeneration (Long, JZ, et al., Nature Chemical Biology 2009, 5, 37). Systemic injection of such inhibitors replicates the Mgll- / - mouse phenotype in the brain, which includes increased 2-AG levels, decreased AA levels and associated eicosanoid production, and suppression of cytokine production and microglial activation after LPS-induced neuroinflammation (Nomura, DK, et al., Science 2011, 334, 809), confirming that MAGL is a target that could lead to new drugs.

[0006] Following genetic and / or pharmacological disruption of MAGL activity, endogenous levels of the MAGL native substrate, 2-AG, increase in the brain. 2-AG has been reported to exhibit beneficial effects, for example, on antinociceptive effects in mice (Ignatowska-Jankowska B. et al., J. Pharmacol. Exp. Ther. 2015, 353, 424.) and on pain induced by mental disorders such as depression in chronic stress models (Zhong P. et al., Neuropsychopharmacology 2014, 39, 1763.).

[0007] Furthermore, oligodendrocytes (OLs) and their precursors (OPCs), myelinated cells of the central nervous system, express cannabinoid receptor 2 (CB2) on their membranes. CB2-AG is an endogenous ligand for CB1 and CB2 receptors. It has been reported that both cannabinoids and pharmacological inhibition of MAGL may reduce the vulnerability of OLs and OPCs to excitotoxic injury and thus be neuroprotective (Bernal-Chico, A., et al., Glia 2015, 63, 163). In addition, pharmacological inhibition of MAGL increased the number of myelinated OLs in the mouse brain, suggesting that MAGL inhibition may promote OPC differentiation in myelinated OLs in vivo (Alpar, A., et al., Nature communications 2014, 5, 4421). Inhibition of MAGL has also been shown to promote remyelination and functional recovery in a mouse model of progressive multiple sclerosis (Feliu A. et al., Journal of Neuroscience 2017, 37(35), 8385).

[0008] Furthermore, metabolism, particularly lipid metabolism, has become extremely important in cancer research in recent years. Researchers believe that novel fatty acid synthesis plays a crucial role in tumor development. Numerous studies have shown that endocannabinoids possess antitumor effects, including antiproliferative, apoptosis-inducing, and antimetastatic effects. MAGL, as a key degrading enzyme for both lipid metabolism and the endocannabinoid system, also contributes to various aspects of tumorigenesis, including glioblastoma, as part of its gene expression characteristics (Qin, H., et al., Cell Biochem. Biophys. 2014, 70, 33; Nomura DK et al., Cell 2009, 140(1), 49-61; Nomura DK et al., Chem. Biol. 2011, 18(7), 846-856; Jinlong Yin et al, Nature Communications 2020, 11, 2978).

[0009] The endogenous cannabinoid system is also involved in many gastrointestinal physiological and physiological-pathological effects (Marquez, Suarez et al. 2009). All of these effects are driven primarily by cannabinoid receptors (CBRs), CB1 and CB2. CB1 receptors are present throughout the gastrointestinal tract of animals and healthy humans, particularly in the enteric nervous system (ENS) and lining epithelium, as well as in the smooth muscle cells of blood vessels in the colon wall (Wright, Rooney et al. 2005), (Duncan, Davison et al. 2005). Activation of CB1 results in antiemetic, anti-motility, and anti-inflammatory effects, and helps regulate pain (Perisetti, Rimu et al. 2020). CB2 receptors are expressed in plasma cells and immune cells such as macrophages, in the lamina propria of the gastrointestinal mucosa (Wright, Rooney et al., 2005), and in the epithelium of human colon tissue, primarily associated with inflammatory bowel disease (IBD). Activation of CB2 exerts anti-inflammatory effects by reducing pro-inflammatory cytokines. MAGL expression is increased in the colon tissue of UC patients (Marquez, Suarez et al. 2009), and 2-AG levels are increased in the plasma of IBD patients (Grill, Hogenauer et al. 2019). Several animal studies have demonstrated the potential of MAGL inhibitors for the symptomatic treatment of IBD. MAGL inhibition prevents TNBS-induced mouse colitis and reduces local and circulating inflammatory markers via CB1 / CB2 MoA (Marquez, Suarez et al. 2009). Furthermore, MAGL inhibition improves intestinal wall integrity and intestinal permeability via CB1-driven MoA (Wang, Zhang et al. 2020). [Overview of the Initiative] [Problems that the invention aims to solve]

[0010] In conclusion, inhibiting the action and / or activation of MAGL is a promising new therapeutic strategy for treating or preventing neuroinflammation, neurodegenerative diseases, pain, cancer, psychiatric disorders, inflammatory bowel disease, abdominal pain, and abdominal pain associated with irritable bowel syndrome. Furthermore, inhibiting the action and / or activation of MAGL is a promising new therapeutic strategy for achieving neuroprotection and myelin regeneration. Thus, there is a high unmet medical need for new MAGL inhibitors. [Means for solving the problem]

[0011] In a first embodiment, the present invention relates to formula (I) [ka] (In the formula, A, B, X and R 1 ~R 7 (as defined herein) The compound is provided.

[0012] In a further embodiment, the present invention provides a method for producing a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, as described in any one of schemes 1 to 44.

[0013] In a further embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, when prepared according to the method described herein.

[0014] In a further embodiment, the present invention provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, for use as therapeutic agents.

[0015] In a further embodiment, the present invention provides a pharmaceutical composition comprising a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, and a therapeutically inactive carrier.

[0016] In a further embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, for use in a method for inhibiting monoacylglycerol lipase in mammals.

[0017] In a further embodiment, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, for use in the treatment or prevention of neuroinflammation, neurodegenerative diseases, pain, cancer, mental disorders and / or inflammatory bowel disease in mammals.

[0018] In a further embodiment, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, for use in the treatment or prevention of multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, anxiety, migraine, depression, hepatocellular carcinoma, colon cancer, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, pain-related spasticity, abdominal pain, abdominal pain associated with irritable bowel syndrome, and / or visceral pain in mammals. [Modes for carrying out the invention]

[0019] Detailed description of the invention definition Features, integers, characteristics, compounds, chemical parts, or groups described in relation to specific aspects, embodiments, or examples of the present invention should be understood to be applicable to any other aspects, embodiments, or examples described herein, unless they are incompatible. All features disclosed herein (including any appended claims, abstract, and drawings) and / or all steps of any method or process so so disclosed may be combined in any combination, except for combinations in which at least some of such features and / or steps are mutually exclusive. The present invention is not limited to the details of any of the embodiments described above. The present invention extends to any novel features or any novel combination of features disclosed herein (including any appended claims, abstract, and drawings), or any novel steps or any novel combination of any method or process so so disclosed.

[0020] The term "alkyl" refers to a monovalent or polyvalent linear or branched saturated hydrocarbon group having 1 to 12 carbon atoms, for example. In some preferred embodiments, the alkyl group has 1 to 6 carbon atoms ("C"). 1~6 Alkyl groups, for example, contain 1, 2, 3, 4, 5, or 6 carbon atoms. In other embodiments, alkyl groups contain 1 to 3 carbon atoms, for example, 1, 2, or 3 carbon atoms. Some non-limiting examples of alkyl groups include methyl, ethyl, propyl, 2-propyl (isopropyl), n-butyl, isobutyl, sec-butyl, tert-butyl, and 2,2-dimethylpropyl. Particularly preferred but non-limiting examples of alkyl groups are methyl, tert-butyl, and 2,2-dimethylpropyl.

[0021] The term "alkoxy" refers to the alkyl group defined above, bonded to the parent molecule via an oxygen atom. Unless otherwise specified, an alkoxy group contains 1 to 12 carbon atoms. In some preferred embodiments, the alkoxy group contains 1 to 6 carbon atoms ("C"). 1~6This includes "alkoxy". In other embodiments, the alkoxy group contains 1 to 4 carbon atoms. In yet another embodiment, the alkoxy group contains 1 to 3 carbon atoms. Some non-limiting examples of alkoxy groups include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, and tert-butoxy. A particularly preferred but non-limiting example of an alkoxy is methoxy.

[0022] The terms "halogen" or "halo" refer to fluoro(F), chloro(Cl), bromo(Br), or iodine(I). Preferably, the terms "halogen" or "halo" refer to fluoro(F), chloro(Cl), or bromo(Br). Particularly preferred but non-limiting examples of "halogen" or "halo" are fluoro(F) and chloro(Cl).

[0023] As used herein, the term "cycloalkyl" refers to a monocyclic or bicyclic hydrocarbon group having 3 to 10 ring carbon atoms, being saturated or partially unsaturated ("C"). 3-10 "Cycloalkyl"). In some preferred embodiments, the cycloalkyl group is a saturated monocyclic hydrocarbon group having 3 to 8 ring carbon atoms. "Bicyclic cycloalkyl" refers to a cycloalkyl moiety consisting of two saturated carbon rings having two common carbon atoms, i.e., the bridging separating the two rings is either a single bond or a chain of one or two ring atoms, and a spirocyclic moiety, i.e., a cycloalkyl moiety in which the two rings are linked via one common ring atom. Preferably, the cycloalkyl group is a saturated monocyclic hydrocarbon group having 3 to 6 ring carbon atoms, e.g., 3, 4, 5, or 6 carbon atoms. Some non-limiting examples of cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 1-bicyclo[1.1.1]pentanyl, norbornanyl, and 1-bicyclo[2.2.2]octanyl. A particularly preferred, but non-limiting, example of a cycloalkyl is cyclopropyl.

[0024] The term "aryl" refers to a total of 6-14 ring members ("C6-C6").14 An aryl is a monocyclic, bicyclic, or tricyclic carbocyclic ring system having 6 to 12 ring members, more preferably 6 to 10 ring members, wherein at least one ring in the system is aromatic. Some non-limiting examples of aryls include phenyl and 9H-fluorenyl (e.g., 9H-fluoren-9-yl). A particularly preferred, but non-limiting, example of an aryl is phenyl.

[0025] The term "haloaryl" refers to an aryl group in which at least one hydrogen atom of the aryl group is substituted with a halogen atom, preferably a fluorohydrogen atom. Preferably, "haloaryl" refers to an aryl group in which one, two, or three hydrogen atoms of the aryl group are substituted with halogen atoms, most preferably a fluorohydrogen atom. A particularly preferred but non-limiting example of a haloaryl is fluorophenyl.

[0026] The term "heteroaryl" refers to a monovalent or polyvalent monocyclic, bicyclic, or tricyclic, preferably bicyclic, ring system having a total of 5 to 14 ring members, preferably 5 to 12 ring members, more preferably 5 to 10 ring members, wherein at least one ring in the system is aromatic, and at least one ring in the system contains one or more heteroatoms. Preferably, "heteroaryl" refers to a 5- to 10-membered heteroaryl containing 1, 2, 3, or 4 heteroatoms independently selected from O, S, and N. Most preferably, "heteroaryl" refers to a 5- to 10-membered heteroaryl containing 1 to 2 heteroatoms independently selected from O, S, and N.Some non-restrictive examples of heteroaryls include spiro[cyclopropane-1,3'-indoline] (e.g., spiro[cyclopropane-1,3'-indoline]-1'-yl), 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazine-2-yl, pyrimidine-2-yl, pyrimidine-4-yl, pyrimidine-5-yl, pyrimidine-6-yl, indole-1-yl, 1H-indole-2-yl, 1H-indole-3-yl, 1H-indole 1H-indole-4-yl, 1H-indole-5-yl, 1H-indole-6-yl, 1H-indole-7-yl, 1,2-benzoxazole-3-yl, 1,2-benzoxazole-4-yl, 1,2-benzoxazole-5-yl, 1,2-benzoxazole-6-yl, 1,2-benzoxazole-7-yl, 1H-indazole-3-yl, 1H-indazole-4-yl, 1H-indazole-5-yl, 1H-indazole-6-yl, 1H- Ndazole-7-yl, pyrazole-1-yl, 1H-pyrazole-3-yl, 1H-pyrazole-4-yl, 1H-pyrazole-5-yl, imidazole-1-yl, 1H-imidazole-2-yl, 1H-imidazole-4-yl, 1H-imidazole-5-yl, oxazole-2-yl, oxazole-4-yl, oxazole-5-yl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, thiazole-2-yl, thiazole Examples include -4-yl, thiazole-5-yl, pyridazine-3-yl, pyridazine-4-yl, 1,2,4-triazole-4-yl, 1,2,4-triazole-1-yl, 4H-1,2,4-triazole-3-yl, 4,5,6,7-tetrahydroindazole-2-yl, 6,7-dihydro-4H-pyrano[4,3-c]pyrazole-2-yl, thiazolyl, benzofuran-4-yl, tetrathiazolyl, isoxazolyl, and morpholinil. Particularly preferred but non-limiting examples of heteroaryls are pyridyl, pyrazinyl, pyrimidinyl, pyrazolyl, imidazolyl, oxazolyl, oxadiazolyl, and triazolyl.

[0027] The term "heterocyclyl" refers to a saturated or partially unsaturated monocyclic or bicyclic ring system, preferably a monocyclic ring system, having 3 to 14 ring atoms, preferably 3 to 10 ring atoms, more preferably 3 to 8 ring atoms, where 1, 2, or 3 of the ring atoms are heteroatoms selected from N, O, and S, and the remaining ring atoms are carbon. Preferably, 1 to 2 of the ring atoms are selected from N and O, and the remaining ring atoms are carbon. A "bicyclic heterocyclyl" refers to a heterocyclic portion consisting of two rings having two common ring atoms, i.e., a spirocyclic portion, i.e., a heterocyclic portion in which the two rings are joined via one common ring atom, where the bridge separating the two rings is either a single bond or a chain of one or two ring atoms. Some non-limiting examples of heterocyclyl groups include azetidinyl, piperidyl, pyrrolidinyl, oxetanyl, 5-azaspiro[2.5]octan-5-yl, piperidyl, 3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl, 2-azaspiro[3.3]heptan-2-yl, 2,6-diazaspiro[3.3]heptanyl, 2-azaspiro[3.5]nonane-2-yl, 1,2-dihydropyridiin, piperidyl, pyrrolidinyl, tetrahydrothiophenyl, and thietanyl.

[0028] The term "hydroxy" refers to the -OH group.

[0029] The term "cyano" refers to the -CN (nitrile) group.

[0030] The term "amino" refers to the -NH2 group.

[0031] The term "carboxy" refers to the -COOH group (i.e., a carboxylic acid group).

[0032] The term "alkoxycarbonyl" refers to a -C(O)-O-C1~C6 alkyl group (i.e., a carboxylic acid ester group).

[0033] The term "oxo" refers to double-bonded oxygen (=O).

[0034] The term "carbamoyl" refers to the group H2N-C(O)-.

[0035] The term "haloalkyl" refers to an alkyl group in which at least one hydrogen atom of the alkyl group is replaced by a halogen atom, preferably a fluoro atom. Preferably, "haloalkyl" refers to an alkyl group in which one, two, or three hydrogen atoms of the alkyl group are replaced by a halogen atom, most preferably a fluoro atom. Particularly preferred but non-limiting examples of haloalkyls are trifluoromethyl, difluoromethyl, 1,1-difluoroethyl, 2,2-difluoroethyl, and 2,2,2-trifluoroethyl.

[0036] The term "haloalkoxy" refers to an alkoxy group in which at least one of the hydrogen atoms of the alkoxy group is replaced by a halogen atom, preferably a fluoro atom. Preferably, "haloalkoxy" refers to an alkoxy group in which one, two, or three of the hydrogen atoms of the alkoxy group are replaced by halogen atoms, most preferably a fluoro atom. Particularly preferred but non-limiting examples of haloalkoxys are trifluoromethoxy, difluoromethoxy, 2,2,2-trifluoro-1,1-dimethylethoxy, (1,1,1-trifluoropropan-2-yl)oxy, and 2,2,2-trifluoroethoxy.

[0037] The term "pharmaceutically acceptable salt" refers to a salt that retains the biological efficacy and properties of a free base or free acid, and is not biologically or otherwise undesirable. Salts are formed from inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and especially hydrochloric acid, as well as organic acids, such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, N-acetylcysteine, and the like. Furthermore, these salts can be prepared by adding an inorganic base or organic base to a free acid. Salts derived from inorganic bases include, but are not limited to, sodium salts, potassium salts, lithium salts, ammonium salts, calcium salts, and magnesium salts. Salts derived from organic bases include, but are not limited to, primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, and basic ion exchange resins such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, lysine, arginine, N-ethylpiperidine, piperidine, and polyimine resins.

[0038] The compound of formula (I) may contain several chiral centers and may exist as an optically pure enantiomer, a mixture of enantiomers such as a racemate, an optically pure diastereoisomer, a mixture of diastereoisomers, a diastereoisomer racemate, or a mixture of diastereoisomer racemates.

[0039] According to the Cahn-Ingold-Prelog rule, an asymmetric carbon atom can have either an "R" or "S" configuration.

[0040] The abbreviation "MAGL" refers to the enzyme monoacylglycerol lipase. The terms "MAGL" and "monoacylglycerol lipase" are used interchangeably in this specification.

[0041] The term “treatment,” as used herein, includes: (1) suppressing a symptom, disorder, or condition (e.g., in the case of maintenance treatment, stopping, reducing, or delaying the onset or recurrence of at least one clinical symptom or asymptomatic disease); and / or (2) alleviating a condition (i.e., causing a regression of a symptom, disorder, or condition, or at least one of its clinical symptoms or asymptomatics). The benefit to the treated patient is either statistically significant or at least recognizable to the patient or physician. However, it will be understood that when a medicine is administered to a patient to treat a disease, the outcome does not necessarily have to be an effective treatment.

[0042] As used herein, the term “prevention” includes, in mammals, preventing or delaying the onset of clinical symptoms of a condition, disorder or condition that develops in humans who are suffering from or susceptible to a condition, disorder or condition but have not yet experienced or shown any clinical symptoms or asymptomatic symptoms of that condition, disorder or condition.

[0043] As used herein, the term “neuroinflammation” refers to acute and chronic inflammation of nerve tissue, which is the major tissue component of the two parts of the nervous system: the brain and spinal cord of the central nervous system (CNS), and the branched peripheral nerves of the peripheral nervous system (PNS). Chronic neuroinflammation is associated with neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. Acute neuroinflammation usually occurs immediately after injury to the central nervous system, for example, as a result of traumatic brain injury (TBI).

[0044] The term "traumatic brain injury" (also known as "TBI" or "intracranial injury") refers to brain damage resulting from external mechanical forces such as rapid acceleration or deceleration, impact, blast, or penetration by a projectile.

[0045] The term “neurodegenerative disease” refers to diseases that involve the progressive loss of structure or function of neurons, including neuronal death. Examples of neurodegenerative diseases include, but are not limited to, multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis.

[0046] The term “mental disorder” (also called mental illness or psychiatric disorder) relates to behavioral or mental patterns that may cause distress or dysfunction in life. Such features may occur as persistent, recurrent, and remittent episodes, or as single episodes. Examples of mental disorders include, but are not limited to, anxiety disorders and depression.

[0047] The term “pain” refers to an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Examples of pain include, but are not limited to, nociceptive pain, chronic pain (including idiopathic pain), neuropathic pain including chemotherapy-induced neuropathy, phantom limb pain, and psychogenic pain. A specific example of pain is neuropathic pain, which is caused by injury or disease affecting any part of the nervous system involved in bodily feelings (i.e., the somatosensory system). In one embodiment, “pain” is neuropathic pain resulting from amputation or thoracotomy. In one embodiment, “pain” is chemotherapy-induced neuropathy.

[0048] The term "neurotoxicity" relates to toxicity in the nervous system. This occurs when exposure to naturally occurring or artificially produced toxic substances (neurotoxins) alters the normal activity of the nervous system and causes damage to nerve tissue. Examples of neurotoxicity include, but are not limited to, exposure to substances used in chemotherapy, radiation therapy, drug therapy, drug abuse, and organ transplantation, as well as neurotoxicity resulting from exposure to heavy metals, certain foods and food additives, pesticides, industrial and / or cleaning solvents, cosmetics, and some naturally occurring substances.

[0049] The term "cancer" refers to a disease characterized by the presence of a neoplasm or tumor, which is caused by abnormal and uncontrolled proliferation of cells (such cells are "cancer cells"). As used herein, the term "cancer" explicitly includes, but is not limited to, hepatocellular carcinoma, colorectal carcinogenesis, and ovarian cancer.

[0050] As used herein, the term "mammal" includes both humans and non-humans, including, but not limited to, humans, non-human primates, dogs, cats, mice, cows, horses, and pigs. In particularly preferred embodiments, the term "mammal" refers to a human.

[0051] The compounds of the present invention In a first aspect, the present invention provides a compound of formula (I)

Chemical formula

Chemical formula

[0052] In one embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. X is CR 8 And, A is C6~C 14 Aryl, C3~C 10 Selected from cycloalkyl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl, B is B-1 to B-6: [ka] (The wavy lines indicate the connection points to the rest of equation (I)) A heteroaryl selected from, C is C6~C 14 Aryl, C3~C 10 Selected from cycloalkyl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl, L 1 is a covalent bond, -CR 12 R 13 -, -CH2O-, -OCH2-, -CH2NH-, -NHCH2-, -CH2OCH2-, -O-, -NH-, [ka] Selected from -SO2NH-, -NHSO2-, -SO2NHCH2-, -CH2NHSO2-, -SO2-, -CH2SO2-, -SO2CH2-, -(CH2)2SO2-, -SO2(CH2)2-, carbonyl, -NHC(O)-, and -C(O)NH-, R 1 hydrogen, halogen, [ka] C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, C1-C6 alkyl-SO2NH-, C3-C 10 Selected from cycloalkyl-C1~C6alkyl-S(O)2-, C1~C6alkyl-SO2-, halo-C1~C6alkyl-S(O)2-, (C1~C6alkyl)2N-SO2-, and halo-C1~C6alkyl-C(O)-, R 2 , R 3 , and R 4 Each of these is independently selected from hydrogen, halogen, C1-C6 alkyl, halo-C1-C6 alkyl, and 3- to 14-membered heterocyclines. R 5 and R 6These are, independently, hydrogen, halogen, cyano, hydroxyl, amino, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, halo-C1-C6 alkoxy, and C3-C 10 Selected from cycloalkyl and 3- to 14-membered heterocyclines, C3~C 10 Cycloalkyl and 3- to 14-membered heterocyclyls are optionally substituted with one, two, or three substituents selected from C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, halogen, cyano, amino, and hydroxy. R 7 It is either absent, or selected from hydrogen, halogen, cyano, hydroxy, amino, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, and halo-C1-C6 alkoxy. R 8 These are selected from hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy and hydroxy, R 9 These are hydrogen, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, halo-C1-C6 alkoxy, halogen, cyano, SF5, C3-C 10 Cycloalkyl, C3-C 10 Cycloalkyl-C1~C6 alkyl-, 3-membered~14-membered heterocyclyl, C6~C 14 Selected from aryl, C1-C6 alkyl-SO2-, amino, carboxy, carboxy-C1-C6 alkyl, C1-C6 alkoxycarbonyl, C1-C6 alkoxycarbonyl-C1-C6 alkyl-, NH2SO2-, carbamoyl, C1-C6 alkyl-C(O)NH-, halo-C1-C6 alkyl-NHC(O)- and oxo, C3-C 10 Cycloalkyl, 3-membered to 14-membered heterocyclyl, and C6-C 14 The aryl group is optionally substituted with one, two, or three substituents selected from C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, 3- to 14-membered heterocyclyl, halogen, cyano, amino, and hydroxy. R10 and R 11 Each of these is independently selected from hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, and oxo. R 12 These are hydrogen, carbamoyl, C1-C6 alkyl-NHC(O)- and halo-C6-C 14 Selected from the aryl, R 13 is hydrogen, or R 12 and R 13 These, together with the carbon atoms to which they are bonded, C3~C 10 It forms a cycloalkyl group.

[0053] In one embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. A is C6~C 14 Aryl, C3~C 10 Selected from cycloalkyl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl, C is C6~C 14 Aryl, C3~C 10 Selected from cycloalkyl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl, L 1 is a covalent bond, -CR 12 R 13 -, -CH2O-, -CH2NH-, -CH2OCH2-, -O-, -NH-, [ka] Selected from -SO2NH-, -NHSO2-, -SO2NHCH2-, -CH2NHSO2-, -SO2-, -CH2SO2-, -(CH2)2SO2-, carbonyl, and -C(O)NH-, R 1 teeth, [ka] Halo-C1-C6 alkoxy, C1-C6 alkyl-SO2NH-, C3-C 10 Cycloalkyl-C1-C6 alkyl-S(O)2-, C1-C6 alkyl-SO2-, halo-C1-C6 alkyl-S(O)2-, (C1-C6 alkyl)2N-SO2-, and halo-C1-C6 alkyl-C(O)-, selected from R 2 is selected from hydrogen, halogen, C1-C6 alkyl, halo-C1-C6 alkyl, and 3- to 14-member heterocyclyl, R 3 is selected from hydrogen and halogen, R 4 is hydrogen, R 9 is hydrogen, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, halo-C1-C6 alkoxy, halogen, cyano, SF5, C3-C 10 Cycloalkyl, C3-C 10 Cycloalkyl-C1-C6 alkyl-, 3- to 14-member heterocyclyl, C6-C 14 Aryl, C1-C6 alkyl-SO2-, amino, carboxy, carboxy-C1-C6 alkyl, C1-C6 alkoxycarbonyl, C1-C6 alkoxycarbonyl-C1-C6 alkyl-, NH2SO2-, carbamoyl, C1-C6 alkyl-C(O)NH-, halo-C1-C6 alkyl-NHC(O)- and oxo, selected from C3-C 10 Cycloalkyl, 3- to 14-member heterocyclyl and C6-C 14 Aryl is optionally substituted with one or two substituents selected from halo-C1-C6 alkyl, 3- to 14-member heterocyclyl, halogen and hydroxy, R 10 is selected from hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, and oxo, R 11 is selected from hydrogen and halogen, R 12 is hydrogen, carbamoyl, C1-C6 alkyl-NHC(O)- and halo-C6-C 14Selected from the aryl, R 13 is hydrogen, or R 12 and R 13 These, together with the carbon atoms to which they are bonded, C3~C 10 It forms a cycloalkyl group.

[0054] In preferred embodiments, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. A is C6~C 14 Selected from aryls, 5-14 member heteroaryls, and 3-14 member heterocyclines, C is C6~C 14 Aryl, C3~C 10 Selected from cycloalkyl and 5- to 14-membered heteroaryls, L 1 is a covalent bond, -CR 12 R 13 -, -CH2O-, -O-, -SO2NH-, and -SO2- are selected. R 1 teeth, [ka] And, R 2 These are selected from hydrogen and C1-C6 alkyl groups. R 3 , R 4 , R 12 , and R 13 It is all hydrogen, R 9 These include C1-C6 alkyl, halo-C1-C6 alkyl, halo-C1-C6 alkoxy, SF5, and C3-C 10 Selected from cycloalkyl, 3- to 14-membered heterocyclyl, and C1-C6 alkyl-SO2-, and C3-C 10 Cycloalkyl and 3- to 14-membered heterocyclyls are optionally substituted with one or two substituents selected from halo-C1 to C6 alkyl and hydroxyl groups. R 10These are selected from hydrogen, halogens, and C1-C6 alkoxys. R 11 The element is selected from hydrogen and halogens.

[0055] In particularly preferred embodiments, the present invention provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof. A is selected from phenyl, pyridyl, azetidinyl, 2-azaspiro[3.3]heptan-2-yl, 2,6-diazaspiro[3.3]heptanyl, and 2-azaspiro[3.5]nonan-2-yl, C is selected from phenyl, cyclopropyl, pyridyl, 1,2,4-oxadiazolyl, pyrazinyl, and pyrimidinyl. L 1 is a covalent bond, -CR 12 R 13 -, -CH2O-, -O-, -SO2NH-, and -SO2- are selected. R 1 teeth, [ka] And, R 2 It is selected from hydrogen and methyl, R 3 , R 4 , R 12 , and R 13 It is all hydrogen, R 9 The compound is selected from tert-butyl, CF3, CF3O, SF5, cyclopropyl, azetidinyl, pyrrolidinyl, and methylsulfonyl, and cyclopropyl, azetidinyl, and pyrrolidinyl are optionally substituted with one or two substituents selected from CF3 and hydroxyl. R 10 It is selected from hydrogen, fluoro, chloro and methoxy, R 11 It is selected from hydrogen and fluorocarbon.

[0056] In one embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. A is [ka] Selected from.

[0057] In one embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. A is [ka] Selected from.

[0058] In preferred embodiments, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. A is [ka] Selected from.

[0059] In one embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. A is [ka] Selected from, C is C6~C 14 Aryl, C3~C 10 Selected from cycloalkyl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl, D is C3~C 10 Cycloalkyl, 3-membered to 14-membered heterocyclyl, C6-C 14 Selected from aryls and 5- to 14-membered heteroaryls, E is C3~C 10 Selected from cycloalkyl and 3- to 14-membered heterocyclines, L 1 is a covalent bond, -CR 12 R 13 -, -CH2O-, -CH2NH-, -CH2OCH2-, -O-, -NH-, [ka] Selected from -SO2NH-, -NHSO2-, -SO2NHCH2-, -CH2NHSO2-, -SO2-, -CH2SO2-, -(CH2)2SO2-, carbonyl, and -C(O)NH-, L 2 The following are selected from covalent bonds, -CH2-, -CH2NH-, -NHCH2-, -NH-, -N(C1~C6 alkyl)-, and -SO2-. L 3 It is selected from covalent bonds and -CH2-, R 1 teeth, [ka] Halo-C1~C6 alkoxy, C1~C6 alkyl-SO2NH-, C3~C 10 Selected from cycloalkyl-C1~C6alkyl-S(O)2-, C1~C6alkyl-SO2-, halo-C1~C6alkyl-S(O)2-, (C1~C6alkyl)2N-SO2-, and halo-C1~C6alkyl-C(O)-, R 2 These are selected from hydrogen, halogens, C1-C6 alkyl groups, halo-C1-C6 alkyl groups, and 3- to 14-membered heterocyclines. R 3 It is selected from hydrogen and halogens. R 4 It is hydrogen, R 9These include hydrogen, C1~C6 alkyl, C1~C6 alkoxy, halo-C1~C6 alkyl, halo-C1~C6 alkoxy, halogen, cyano, SF5, C1~C6 alkyl-SO2-, halo-C1~C6 alkyl-SO2-, (C1~C6 alkyl)2-PO-, amino, carboxy, carboxy-C1~C6 alkyl, C1~C6 alkoxycarbonyl, C1~C6 alkoxycarbonyl-C1~C6 alkyl-, NH2SO2-, carbamoyl, C1~C6 alkyl-C(O)NH-, halo-C1~C6 alkyl-NHC(O)-, oxo, [ka] [ka] and [ka] Selected from C3~C 10 Cycloalkyl, 3-membered to 14-membered heterocyclyl and C6-C 14 The aryl group is optionally substituted with one or two substituents selected from halo-C1-C6 alkyl groups, 3- to 14-membered heterocyclines, halogens, and hydroxyls. R 10 These are selected from hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, and oxo. R 11 It is selected from hydrogen and halogens. R 12 These are hydrogen, carbamoyl, C1-C6 alkyl-NHC(O)- and halo-C6-C 14 Selected from the aryl, R 13 is hydrogen, or R 12 and R 13 However, together with the carbon atoms to which they are bonded, C3~C 10 Forming a cycloalkyl group, R 14These are hydrogen, C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, halogen, cyano, amino, carbamoyl, hydroxy, oxo, C1-C6 alkyl-SO2-, [ka] Selected from, R 15 These are selected from hydrogen, halogen, hydroxyl, oxo, and C1-C6 alkyl groups. R 16 It is selected from hydrogen and halogens. R 17 The element is selected from hydrogen, C1-C6 alkyl, and halo-C1-C6 alkyl.

[0060] In one embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. A is [ka] Selected from, C is C6~C 14 Aryl, C3~C 10 Selected from cycloalkyl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl, D is C3~C 10 Cycloalkyl, 3-membered to 14-membered heterocyclyl, C6-C 14 Selected from aryls and 5- to 14-membered heteroaryls, E is C3~C 10 Selected from cycloalkyl and 3- to 14-membered heterocyclines, L 1 is a covalent bond, -CR 12 R 13 -, -CH2O-, -CH2NH-, -CH2OCH2-, -O-, -NH-, [ka] Selected from -SO2NH-, -NHSO2-, -SO2NHCH2-, -CH2NHSO2-, -SO2-, -CH2SO2-, -(CH2)2SO2-, carbonyl, and -C(O)NH-, L 2 The following are selected from covalent bonds, -CH2-, -CH2NH-, -NHCH2-, -NH-, -N(C1~C6 alkyl)-, and -SO2-. L 3 It is selected from covalent bonds and -CH2-, R 1 teeth, [ka] Halo-C1~C6 alkoxy, C1~C6 alkyl-SO2NH-, C3~C 10 Selected from cycloalkyl-C1~C6alkyl-S(O)2-, C1~C6alkyl-SO2-, halo-C1~C6alkyl-S(O)2-, (C1~C6alkyl)2N-SO2-, and halo-C1~C6alkyl-C(O)-, R 2 These are selected from hydrogen, halogens, C1-C6 alkyl groups, halo-C1-C6 alkyl groups, and 3- to 14-membered heterocyclines. R 3 It is selected from hydrogen and halogens. R 4 It is hydrogen, R 9 These include hydrogen, C1~C6 alkyl, C1~C6 alkoxy, halo-C1~C6 alkyl, halo-C1~C6 alkoxy, halogen, cyano, SF5, C1~C6 alkyl-SO2-, halo-C1~C6 alkyl-SO2-, (C1~C6 alkyl)2-PO-, amino, carboxy, carboxy-C1~C6 alkyl, C1~C6 alkoxycarbonyl, C1~C6 alkoxycarbonyl-C1~C6 alkyl-, NH2SO2-, carbamoyl, C1~C6 alkyl-C(O)NH-, halo-C1~C6 alkyl-NHC(O)-, oxo, [ka] [ka] and [ka] Selected from C3~C 10 Cycloalkyl, 3-membered to 14-membered heterocyclyl and C6-C 14 The aryl group is optionally substituted with one or two substituents selected from halo-C1-C6 alkyl groups, 3- to 14-membered heterocyclines, halogens, and hydroxyls. R 10 These are selected from hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, and oxo. R 11 It is selected from hydrogen and halogens. R 12 These are hydrogen, carbamoyl, C1-C6 alkyl-NHC(O)- and halo-C6-C 14 Selected from the aryl, R 13 is hydrogen, or R 12 and R 13 However, together with the carbon atoms to which they are bonded, C3~C 10 Forming a cycloalkyl group, R 14 These are hydrogen, C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, halogen, cyano, amino, carbamoyl, hydroxy, oxo, C1-C6 alkyl-SO2-, [ka] Selected from, R 15 These are selected from hydrogen, halogen, hydroxyl, oxo, and C1-C6 alkyl groups. R 16 It is selected from hydrogen and halogens. R 17The element is selected from hydrogen, C1-C6 alkyl, and halo-C1-C6 alkyl.

[0061] In preferred embodiments, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. A is [ka] Selected from, C is C6~C 14 Aryl, C3~C 10 Selected from cycloalkyl and 5- to 14-membered heteroaryls, D is C3~C 10 Selected from cycloalkyl and 3- to 14-membered heterocyclines, L 1 is a covalent bond, -CR 12 R 13 -, -CH2O-, -O-, -SO2NH-, and -SO2- are selected. L 2 It is selected from covalent bonds and -CH2-, R 1 teeth, [ka] And, R 2 These are selected from hydrogen and C1-C6 alkyl groups. R 3 , R 4 , R 12 , and R 13 It is all hydrogen, R 9 These include halogens, C1-C6 alkyls, halo-C1-C6 alkyls, halo-C1-C6 alkoxys, SF5, C1-C6 alkyl-SO2-, [ka] [ka] and [ka] Selected from, R 10 These are selected from hydrogen, halogens, C1-C6 alkyl groups, and C1-C6 alkoxy groups. R 11 It is selected from hydrogen and halogens. R 14 These are selected from hydrogen and halo-C1~C6 alkyl groups. R 15 It is selected from hydrogen and hydroxyl, R 16 It is hydrogen.

[0062] In one embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. A is C6~C 14 Aryl, C3~C 10 Selected from cycloalkyl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl, C is C6~C 14 Aryl, C3~C 10 Selected from cycloalkyl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl, D is C3~C 10 Cycloalkyl, 3-membered to 14-membered heterocyclyl, C6-C 14 Selected from aryls and 5- to 14-membered heteroaryls, E is C3~C 10 Selected from cycloalkyl and 3- to 14-membered heterocyclines, L 1 is a covalent bond, -CR 12 R 13 -, -CH2O-, -CH2NH-, -CH2OCH2-, -O-, -NH-, [ka] Selected from -SO2NH-, -NHSO2-, -SO2NHCH2-, -CH2NHSO2-, -SO2-, -CH2SO2-, -(CH2)2SO2-, carbonyl, and -C(O)NH-, L 2 The following are selected from covalent bonds, -CH2-, -CH2NH-, -NHCH2-, -NH-, -N(C1~C6 alkyl)-, and -SO2-. L 3 It is selected from covalent bonds and -CH2-, R 1 teeth, [ka] Halo-C1~C6 alkoxy, C1~C6 alkyl-SO2NH-, C3~C 10 Selected from cycloalkyl-C1~C6alkyl-S(O)2-, C1~C6alkyl-SO2-, halo-C1~C6alkyl-S(O)2-, (C1~C6alkyl)2N-SO2-, and halo-C1~C6alkyl-C(O)-, R 2 These are selected from hydrogen, halogens, C1-C6 alkyl groups, halo-C1-C6 alkyl groups, and 3- to 14-membered heterocyclines. R 3 It is selected from hydrogen and halogens. R 4 It is hydrogen, R 9 These include hydrogen, C1~C6 alkyl, C1~C6 alkoxy, halo-C1~C6 alkyl, halo-C1~C6 alkoxy, halogen, cyano, SF5, C1~C6 alkyl-SO2-, halo-C1~C6 alkyl-SO2-, (C1~C6 alkyl)2-PO-, amino, carboxy, carboxy-C1~C6 alkyl, C1~C6 alkoxycarbonyl, C1~C6 alkoxycarbonyl-C1~C6 alkyl-, NH2SO2-, carbamoyl, C1~C6 alkyl-C(O)NH-, halo-C1~C6 alkyl-NHC(O)-, oxo, [ka] [ka] and [ka] Selected from C3~C 10 Cycloalkyl, 3-membered to 14-membered heterocyclyl and C6-C 14 The aryl group is optionally substituted with one or two substituents selected from halo-C1-C6 alkyl groups, 3- to 14-membered heterocyclines, halogens, and hydroxyls. R 10 These are selected from hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, and oxo. R 11 It is selected from hydrogen and halogens. R 12 These are hydrogen, carbamoyl, C1-C6 alkyl-NHC(O)- and halo-C6-C 14 Selected from the aryl, R 13 is hydrogen, or R 12 and R 13 These, together with the carbon atoms to which they are bonded, C3~C 10 Forming a cycloalkyl group, R 14 These are hydrogen, C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, halogen, cyano, amino, carbamoyl, hydroxy, oxo, C1-C6 alkyl-SO2-, [ka] Selected from, R 15 These are selected from hydrogen, halogen, hydroxyl, oxo, and C1-C6 alkyl groups. R 16 It is selected from hydrogen and halogens. R 17The element is selected from hydrogen, C1-C6 alkyl, and halo-C1-C6 alkyl.

[0063] In preferred embodiments, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. A is C6~C 14 Selected from aryls, 5-14 member heteroaryls, and 3-14 member heterocyclines, C is C6~C 14 Aryl, C3~C 10 Selected from cycloalkyl and 5- to 14-membered heteroaryls, D is C3~C 10 Selected from cycloalkyl and 3- to 14-membered heterocyclines, L 1 is a covalent bond, -CR 12 R 13 -, -CH2O-, -O-, -SO2NH-, and -SO2- are selected. L 2 It is selected from covalent bonds and -CH2-, R 1 teeth, [ka] And, R 2 These are selected from hydrogen and C1-C6 alkyl groups. R 3 , R 4 , R 12 , and R 13 It is all hydrogen, R 9 These include halogens, C1-C6 alkyls, halo-C1-C6 alkyls, halo-C1-C6 alkoxys, SF5, C1-C6 alkyl-SO2-, [ka] [ka] and [ka] Selected from, R 10 These are selected from hydrogen, halogens, C1-C6 alkyl groups, and C1-C6 alkoxy groups. R 11 It is selected from hydrogen and halogens. R 14 These are selected from hydrogen and halo-C1~C6 alkyl groups. R 15 However, selected from hydrogen and hydroxyl, R 16 It is hydrogen.

[0064] In particularly preferred embodiments, the present invention provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof. A is selected from phenyl, pyridyl, azetidinyl, 2-azaspiro[3.3]heptan-2-yl, 2,6-diazaspiro[3.3]heptanyl, and 2-azaspiro[3.5]nonan-2-yl, C is selected from phenyl, cyclopropyl, pyridyl, 1,2,4-oxadiazolyl, pyrazinyl, and pyrimidinyl. D is selected from cyclopropyl, azetidinil, and pyrrolidinil. L 1 is a covalent bond, -CR 12 R 13 -, -CH2O-, -O-, -SO2NH-, and -SO2- are selected. L 2 It is selected from covalent bonds and -CH2-, R 1 teeth, [ka] And, R 2 It is selected from hydrogen and methyl, R 3 , R 4 , R 12 , and R13 It is all hydrogen, R 9 Fluorochloroterite-butyl CF3, CF3O, SF5, methylsulfonyl [ka] [ka] and [ka] Selected from, R 10 It is selected from hydrogen, fluoro, chloro, CF3, and methoxy. R 11 It is selected from hydrogen and fluoro, R 14 It is selected from hydrogen and CF3, R 15 However, selected from hydrogen and hydroxyl, R 16 It is hydrogen.

[0065] In one embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. B is B-1 to B-6: [ka] (The wavy lines indicate the connection points to the rest of equation (I)) A heteroaryl selected from, R 5 These include hydrogen, halogens, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, and C3-C 10 Selected from cycloalkyls and 3- to 14-membered heterocyclines, the C3-C 10 Cycloalkyl groups are optionally substituted with one C1-C6 alkyl substituent. R6 It is selected from hydrogen and halogens. R 7 However, it either does not exist or is hydrogen.

[0066] In preferred embodiments, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. B, [ka] (The wavy lines indicate the connection points to the rest of equation (I)) And, R 5 C1-C6 alkyl and C3-C 10 Selected from cycloalkyl groups, R 6 It is hydrogen, R 7 It does not exist.

[0067] In particularly preferred embodiments, the present invention provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof. B is [ka] (The wavy lines indicate the connection points to the rest of equation (I)) And, R 5 It is selected from ethyl and cyclopropyl, R 6 It is hydrogen, R 7 It does not exist.

[0068] In one embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. B is B-1 to B-10: [ka] (The wavy lines indicate the connection points to the rest of equation (I)) A heteroaryl selected from, R 5 These include hydrogen, halogens, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, and C3-C 10 Selected from cycloalkyls and 3- to 14-membered heterocyclines, the C3-C 10 The cycloalkyl group is optionally substituted with one substituent selected from hydroxy and C1-C6 alkyl groups. R 6 It is selected from hydrogen and halogens. R 7 It either does not exist or is hydrogen.

[0069] In preferred embodiments, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. B is [ka] (The wavy lines indicate the connection points to the rest of equation (I)) And, R 5 These include C1-C6 alkyl, halo-C1-C6 alkyl, and C3-C 10 Selected from cycloalkyl groups, C3~C 10 The cycloalkyl group is optionally substituted with one hydroxyl substituent. R 6 It is hydrogen, R 7 It does not exist.

[0070] In particularly preferred embodiments, the present invention provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof. B is [ka] (The wavy lines indicate the connection points to the rest of equation (I)) And, R 5 This is selected from ethyl, CF3, and cyclopropyl, and the cyclopropyl is optionally substituted with one hydroxy substituent. R 6 It is hydrogen, R 7 It does not exist.

[0071] In a preferred embodiment, the present invention is R 8 The present specification provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen or hydroxyl.

[0072] In a particularly preferred embodiment, the present invention is R 8 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein the compound is hydrogen.

[0073] In one embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. X is CR 8 or N, R 8 is either hydrogen or hydroxyl.

[0074] In preferred embodiments, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. X is CR 8 And, R 8 It is hydrogen.

[0075] In one embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. A is C6~C 14 Aryl, C3~C 10 Selected from cycloalkyl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl, B is B-1 to B-6: [ka] (The wavy lines indicate the connection points to the rest of equation (I)) A heteroaryl selected from, C is C6~C 14 Aryl, C3~C 10 Selected from cycloalkyl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl, L 1 is a covalent bond, -CR 12 R 13 -, -CH2O-, -CH2NH-, -CH2OCH2-, -O-, -NH-, [ka] Selected from -SO2NH-, -NHSO2-, -SO2NHCH2-, -CH2NHSO2-, -SO2-, -CH2SO2-, -(CH2)2SO2-, carbonyl, and -C(O)NH-, R 1 teeth, [ka] Halo-C1~C6 alkoxy, C1~C6 alkyl-SO2NH-, C3~C 10 Selected from cycloalkyl-C1~C6alkyl-S(O)2-, C1~C6alkyl-SO2-, halo-C1~C6alkyl-S(O)2-, (C1~C6alkyl)2N-SO2-, and halo-C1~C6alkyl-C(O)-, R 2 These are selected from hydrogen, halogens, C1-C6 alkyl groups, halo-C1-C6 alkyl groups, and 3- to 14-membered heterocyclines. R 3 It is selected from hydrogen and halogens. R 4 It is hydrogen, R 5 These include hydrogen, halogens, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, and C3-C 10 Selected from cycloalkyls and 3- to 14-membered heterocyclines, the C3-C10 Cycloalkyl groups are optionally substituted with one C1-C6 alkyl substituent. R 6 It is selected from hydrogen and halogens. R 7 It either does not exist or is hydrogen. R 8 is hydrogen or hydroxyl, R 9 These are hydrogen, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, halo-C1-C6 alkoxy, halogen, cyano, SF5, C3-C 10 Cycloalkyl, C3-C 10 Cycloalkyl-C1~C6 alkyl-, 3-membered~14-membered heterocyclyl, C6~C 14 Selected from aryl, C1-C6 alkyl-SO2-, amino, carboxy, carboxy-C1-C6 alkyl, C1-C6 alkoxycarbonyl, C1-C6 alkoxycarbonyl-C1-C6 alkyl-, NH2SO2-, carbamoyl, C1-C6 alkyl-C(O)NH-, halo-C1-C6 alkyl-NHC(O)- and oxo, C3-C 10 Cycloalkyl, 3-membered to 14-membered heterocyclyl and C6-C 14 The aryl group is optionally substituted with one or two substituents selected from halo-C1-C6 alkyl groups, 3- to 14-membered heterocyclines, halogens, and hydroxyls. R 10 These are selected from hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, and oxo. R 11 It is selected from hydrogen and halogens. R 12 These are hydrogen, carbamoyl, C1-C6 alkyl-NHC(O)- and halo-C6-C 14 Selected from the aryl, R 13 is hydrogen, or R 12 and R 13 These, together with the carbon atoms to which they are bonded, C3~C 10 It forms a cycloalkyl group.

[0076] In preferred embodiments, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. A is C6~C 14 Selected from aryls, 5- to 14-membered heteroaryls, and 3- to 14-membered heterocyclines, B is [ka] (The wavy lines indicate the connection points to the rest of equation (I)) And, C is C6~C 14 Aryl, C3~C 10 Selected from cycloalkyl and 5- to 14-membered heteroaryls, L 1 is a covalent bond, -CR 12 R 13 -, -CH2O-, -O-, -SO2NH-, and -SO2- are selected. R 1 teeth, [ka] And, R 2 These are selected from hydrogen and C1-C6 alkyl groups. R 3 , R 4 , R 6 , R 8 , R 12 and R 13 It is all hydrogen, R 5 C1-C6 alkyl and C3-C 10 Selected from cycloalkyl groups, R 7 It does not exist, R 9 These include C1-C6 alkyl, halo-C1-C6 alkyl, halo-C1-C6 alkoxy, SF5, and C3-C 10 Selected from cycloalkyl, 3- to 14-membered heterocyclyl, and C1-C6 alkyl-SO2-, and C3-C 10Cycloalkyl and 3- to 14-membered heterocyclyls are optionally substituted with one or two substituents selected from halo-C1 to C6 alkyl and hydroxyl groups. R 10 These are selected from hydrogen, halogens, and C1-C6 alkoxys. R 11 The element is selected from hydrogen and halogens.

[0077] In particularly preferred embodiments, the present invention provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof. A is selected from phenyl, pyridyl, azetidinyl, 2-azaspiro[3.3]heptan-2-yl, 2,6-diazaspiro[3.3]heptanyl, and 2-azaspiro[3.5]nonan-2-yl, B is [ka] (The wavy lines indicate the connection points to the rest of equation (I)) And, C is selected from phenyl, cyclopropyl, pyridyl, 1,2,4-oxadiazolyl, pyrazinyl, and pyrimidinyl. L 1 is a covalent bond, -CR 12 R 13 -, -CH2O-, -O-, -SO2NH-, and -SO2- are selected. R 1 teeth, [ka] And, R 2 It is selected from hydrogen and methyl, R 3 , R 4 , R 6 , R 8 , R 12 and R 13 It is all hydrogen, R 5 It is selected from ethyl and cyclopropyl, R 7 It does not exist, R 9 The compound is selected from tert-butyl, CF3, CF3O, SF5, cyclopropyl, azetidinyl, pyrrolidinyl, and methylsulfonyl, and cyclopropyl, azetidinyl, and pyrrolidinyl are optionally substituted with one or two substituents selected from CF3 and hydroxyl. R 10 It is selected from hydrogen, fluoro, chloro and methoxy, R 11 It is selected from hydrogen and fluorocarbon.

[0078] In one embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. X is CR 8 or N, A is C6~C 14 Aryl, C3~C 10 Selected from cycloalkyl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl, B is B-1 to B-10: [ka] (The wavy lines indicate the connection points to the rest of equation (I)) A heteroaryl selected from, C is C6~C 14 Aryl, C3~C 10 Selected from cycloalkyl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl, D is C3~C 10 Cycloalkyl, 3-membered to 14-membered heterocyclyl, C6-C 14 Selected from aryls and 5- to 14-membered heteroaryls, E is C3~C 10 Selected from cycloalkyl and 3- to 14-membered heterocyclines, L 1 is a covalent bond, -CR 12 R 13-, -CH2O-, -CH2NH-, -CH2OCH2-, -O-, -NH-, [ka] Selected from -SO2NH-, -NHSO2-, -SO2NHCH2-, -CH2NHSO2-, -SO2-, -CH2SO2-, -(CH2)2SO2-, carbonyl, and -C(O)NH-, L 2 The following are selected from covalent bonds, -CH2-, -CH2NH-, -NHCH2-, -NH-, -N(C1~C6 alkyl)-, and -SO2-. L 3 It is selected from covalent bonds and -CH2-, R 1 teeth, [ka] Halo-C1~C6 alkoxy, C1~C6 alkyl-SO2NH-, C3~C 10 Selected from cycloalkyl-C1~C6alkyl-S(O)2-, C1~C6alkyl-SO2-, halo-C1~C6alkyl-S(O)2-, (C1~C6alkyl)2N-SO2-, and halo-C1~C6alkyl-C(O)-, R 2 These are selected from hydrogen, halogens, C1-C6 alkyl groups, halo-C1-C6 alkyl groups, and 3- to 14-membered heterocyclines. R 3 It is selected from hydrogen and halogens. R 4 It is hydrogen, R 5 These include hydrogen, halogens, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, and C3-C 10 Selected from cycloalkyls and 3- to 14-membered heterocyclines, the C3-C 10 The cycloalkyl group is optionally substituted with one substituent selected from hydroxy and C1-C6 alkyl groups. R 6 It is selected from hydrogen and halogens. R 7 It either does not exist or is hydrogen. R 8 is hydrogen or hydroxyl, R 9 These include hydrogen, C1~C6 alkyl, C1~C6 alkoxy, halo-C1~C6 alkyl, halo-C1~C6 alkoxy, halogen, cyano, SF5, C1~C6 alkyl-SO2-, halo-C1~C6 alkyl-SO2-, (C1~C6 alkyl)2-PO-, amino, carboxy, carboxy-C1~C6 alkyl, C1~C6 alkoxycarbonyl, C1~C6 alkoxycarbonyl-C1~C6 alkyl-, NH2SO2-, carbamoyl, C1~C6 alkyl-C(O)NH-, halo-C1~C6 alkyl-NHC(O)-, oxo, [ka] [ka] and [ka] Selected from, R 10 These are selected from hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, and oxo. R 11 It is selected from hydrogen and halogens. R 12 These are hydrogen, carbamoyl, C1-C6 alkyl-NHC(O)- and halo-C6-C 14 Selected from the aryl, R 13 is hydrogen, or R 12 and R 13 These, together with the carbon atoms to which they are bonded, C3~C 10 Forming a cycloalkyl group, R 14These are hydrogen, C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, halogen, cyano, amino, carbamoyl, hydroxy, oxo, C1-C6 alkyl-SO2-, [ka] Selected from, R 15 These are selected from hydrogen, halogen, hydroxyl, oxo, and C1-C6 alkyl groups. R 16 It is selected from hydrogen and halogens. R 17 The element is selected from hydrogen, C1-C6 alkyl, and halo-C1-C6 alkyl.

[0079] In preferred embodiments, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. X is CR 8 And, A is C6~C 14 Selected from aryls, 5-14 member heteroaryls, and 3-14 member heterocyclines, B is [ka] (The wavy lines indicate the connection points to the rest of equation (I)) And, C is C6~C 14 Aryl, C3~C 10 Selected from cycloalkyl and 5- to 14-membered heteroaryls, D is C3~C 10 Selected from cycloalkyl and 3- to 14-membered heterocyclines, L 1 is a covalent bond, -CR 12 R 13 -, -CH2O-, -O-, -SO2NH-, and -SO2- are selected. L 2 It is selected from covalent bonds and -CH2-, R 1 teeth, [ka] And, R 2 These are selected from hydrogen and C1-C6 alkyl groups. R 3 , R 4 , R 6 , R 8 , R 12 and R 13 It is all hydrogen, R 5 These include C1-C6 alkyl, halo-C1-C6 alkyl, and C3-C 10 Selected from cycloalkyl groups, C3~C 10 The cycloalkyl group is optionally substituted with one hydroxyl substituent. R 7 It does not exist, R 9 These include halogens, C1-C6 alkyls, halo-C1-C6 alkyls, halo-C1-C6 alkoxys, SF5, C1-C6 alkyl-SO2-, [ka] [ka] and [ka] Selected from, R 10 These are selected from hydrogen, halogens, C1-C6 alkyl groups, and C1-C6 alkoxy groups. R 11 It is selected from hydrogen and halogens. R 14 These are selected from hydrogen and halo-C1~C6 alkyl groups. R 15 However, selected from hydrogen and hydroxyl, R 16It is hydrogen.

[0080] In particularly preferred embodiments, the present invention provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof. X is CR 8 And, A is selected from phenyl, pyridyl, azetidinyl, 2-azaspiro[3.3]heptan-2-yl, 2,6-diazaspiro[3.3]heptanyl, and 2-azaspiro[3.5]nonan-2-yl, B is [ka] (The wavy lines indicate the connection points to the rest of equation (I)) And, C is selected from phenyl, cyclopropyl, pyridyl, 1,2,4-oxadiazolyl, pyrazinyl, and pyrimidinyl. D is selected from cyclopropyl, azetidinil, and pyrrolidinil. L 1 is a covalent bond, -CR 12 R 13 -, -CH2O-, -O-, -SO2NH-, and -SO2- are selected. L 2 It is selected from covalent bonds and -CH2-, R 1 teeth, [ka] And, R 2 It is selected from hydrogen and methyl, R 3 , R 4 , R 6 , R 8 , R 12 and R 13 It is all hydrogen, R 5 This is selected from ethyl, CF3, and cyclopropyl, and the cyclopropyl is optionally substituted with one hydroxy substituent. R 7 It does not exist, R 9 Fluorochloroterite-butyl CF3, CF3O, SF5, methylsulfonyl [ka] [ka] and [ka] Selected from, R 10 It is selected from hydrogen, fluoro, chloro, CF3, and methoxy. R 11 It is selected from hydrogen and fluoro, R 14 It is selected from hydrogen and CF3, R 15 It is selected from hydrogen and hydroxyl, R 16 It is hydrogen.

[0081] In one embodiment, the present invention is that A is C6~C 14 Aryl, C3~C 10 The present invention provides compounds of formula (I) as described herein, selected from cycloalkyls, 5- to 14-membered heteroaryls, and 3- to 14-membered heterocyclines, or pharmaceutically acceptable salts thereof.

[0082] In one embodiment, the present invention has B as B-1 to B-6: [ka] (The wavy lines indicate the connection points to the rest of equation (I)) The present specification provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, which is a heteroaryl selected from the above.

[0083] In one embodiment, the present invention has B-1 to B-10: [ka] (The wavy lines indicate the connection points to the rest of equation (I)) The present specification provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, which is a heteroary selected from the above.

[0084] In one embodiment, the present invention is such that C is C6~C 14 Aryl, C3~C 10 The present invention provides compounds of formula (I) as described herein, selected from cycloalkyls, 5- to 14-membered heteroaryls, and 3- to 14-membered heterocyclines, or pharmaceutically acceptable salts thereof.

[0085] In one embodiment, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein C is selected from phenyl, bicyclo[1.1.1]pentanyl, pyridyl, pyrimidinyl, pyridazinyl, and pyrazinyl.

[0086] In one embodiment, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein D is selected from cyclopropyl, thietanyl, tetrahydrothiophene, azetidinyl, pyrrolidinyl, piperidyl, oxetanyl, phenyl, 1H-1,2,4-triazolyl, 1H-triazolyl, 4H-1,2,4-triazolyl, and 1,3,4-oxadiazolyl.

[0087] In one embodiment, the present invention is such that E is C3~C 10 The present invention provides compounds of formula (I) as described herein, selected from cycloalkyls and 3- to 14-membered heterocyclines, or pharmaceutically acceptable salts thereof.

[0088] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, in which E is selected from cyclopropyl and cyclobutyl.

[0089] In one embodiment, the present invention is L 1 Covalent bond, -CR 12 R 13 -, -CH2O-, -CH2NH-, -CH2OCH2-, -O-, -NH-, [ka] Selected from -SO2NH-, -NHSO2-, -SO2NHCH2-, -CH2NHSO2-, -SO2-, -CH2SO2-, -(CH2)2SO2-, carbonyl, and -C(O)NH-, R 12 and R 13 The present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof.

[0090] In one embodiment, the present invention is L 2 The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein the bond is selected from covalent, -CH2-, -CH2NH-, -NHCH2-, -NH-, -N(C1~C6 alkyl)-, and -SO2-.

[0091] In one embodiment, the present invention is L 3 The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein the bond is selected from covalent bonds and -CH2-.

[0092] In one embodiment, the present invention is R 1 but, [ka] Halo-C1~C6 alkoxy, C1~C6 alkyl-SO2NH-, C3~C 10 Selected from cycloalkyl-C1~C6alkyl-S(O)2-, C1~C6alkyl-SO2-, halo-C1~C6alkyl-S(O)2-, (C1~C6alkyl)2N-SO2-, and halo-C1~C6alkyl-C(O)-, R 9 , R10 , R 11 , L 1 The present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, where C is as defined herein.

[0093] In one embodiment, the present invention is R 2 The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen, halogens, C1-C6 alkyl groups, halo-C1-C6 alkyl groups, and 3- to 14-membered heterocyclines.

[0094] In one embodiment, the present invention is R 3 This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen and halogens.

[0095] In a preferred embodiment, the present invention is R 4 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein the compound is hydrogen.

[0096] In one embodiment, the present invention is R 5 Hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, C3-C 10 Selected from cycloalkyls and 3- to 14-membered heterocyclines, the C3-C 10 The present invention provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein the cycloalkyl group is optionally substituted with one C1-C6 alkyl substituent.

[0097] In one embodiment, the present invention is R 5 Hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, C3-C 10 Selected from cycloalkyls and 3- to 14-membered heterocyclines, the C3-C 10The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein the cycloalkyl group is optionally substituted with one substituent selected from hydroxyl and C1-C6 alkyl groups.

[0098] In one embodiment, the present invention is R 6 This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen and halogens.

[0099] In one embodiment, the present invention is R 7 The present specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein the element is absent or is hydrogen.

[0100] In one embodiment, the present invention is R 8 The present specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein is hydrogen or hydroxyl.

[0101] In one embodiment, the present invention is R 9 Hydrogen, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, halo-C1-C6 alkoxy, halogen, cyano, SF5, C3-C 10 Cycloalkyl, C3-C 10 Cycloalkyl-C1~C6 alkyl-, 3-membered~14-membered heterocyclyl, C6~C 14 -Selected from aryl, C1~C6 alkyl-SO2-, amino, carboxy, carboxy-C1~C6 alkyl, C1~C6 alkoxycarbonyl, C1~C6 alkoxycarbonyl-C1~C6 alkyl-, NH2SO2-, carbamoyl, C1~C6 alkyl-C(O)NH-, halo-C1~C6 alkyl-NHC(O)- and oxo, C3~C 10 Cycloalkyl, 3-membered to 14-membered heterocyclyl and C6-C 14 The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein the aryl is optionally substituted with one or two substituents selected from halo-C1-C6 alkyl, 3- to 14-membered heterocyclyl, halogen, and hydroxyl.

[0102] In one embodiment, the present invention is R 9 Hydrogen, C1~C6 alkyl, C1~C6 alkoxy, halo-C1~C6 alkyl, halo-C1~C6 alkoxy, halogen cyano, SF5, C1~C6 alkyl-SO2-, halo-C1~C6 alkyl-SO2-, (C1~C6 alkyl)2-PO-, amino, carboxy, carboxy-C1~C6 alkyl, C1~C6 alkoxycarbonyl, C1~C6 alkoxycarbonyl-C1~C6 alkyl-, NH2SO2-, carbamoyl, C1~C6 alkyl-C(O)NH-, halo-C1~C6 alkyl-NHC(O)-, oxo, [ka] [ka] and [ka] Selected from, L 2 , D, and R 14 ~R 16 This provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable compound thereof, or a pharmaceutically acceptable salt thereof.

[0103] In one embodiment, the present invention is R 10 The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, and oxo.

[0104] In one embodiment, the present invention is R 11 This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen and halogens.

[0105] In one embodiment, the present invention is R 12 This includes hydrogen, carbamoyl, C1-C6 alkyl-NHC(O)-, and halo-C6-C 14 The following provides compounds of formula (I) as described herein, selected from aryl compounds, or pharmaceutically acceptable salts thereof.

[0106] In a preferred embodiment, the present invention is R 13 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein the compound is hydrogen.

[0107] In one embodiment, the present invention is R 12 and R 13 However, together with the carbon atoms to which they are bonded, C3~C 10 This specification provides compounds of formula (I) described herein that form a cycloalkyl group, or pharmaceutically acceptable salts thereof.

[0108] In a preferred embodiment, the present invention is R 14 hydrogen, C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, halogen, cyano, amino, carbamoyl, hydroxy, oxo, C1-C6 alkyl-SO2- and [ka] Selected from, L 3 , E, and R 17 This provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof.

[0109] In a preferred embodiment, the present invention is R 15 The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen, halogen, hydroxyl, oxo, and C1-C6 alkyl.

[0110] In a preferred embodiment, the present invention is R 16This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen and halogens.

[0111] In a preferred embodiment, the present invention is R 17 The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen, C1-C6 alkyl, and halo-C1-C6 alkyl.

[0112] In a preferred embodiment, the present invention is such that A is C6~C 14 The present invention provides compounds of formula (I) as described herein, selected from aryls, 5- to 14-membered heteroaryls, and 3- to 14-membered heterocyclines, or pharmaceutically acceptable salts thereof.

[0113] In a preferred embodiment, the present invention is that B [ka] (The wavy lines indicate the connection points to the rest of equation (I)) This specification provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof.

[0114] In a preferred embodiment, the present invention relates to C6~C 14 Aryl, C3~C 10 The present invention provides compounds of formula (I) as described herein, selected from cycloalkyls and 5- to 14-membered heteroaryls, or pharmaceutically acceptable salts thereof.

[0115] In a preferred embodiment, the present invention has D = C3~C 10 The present invention provides compounds of formula (I) as described herein, selected from cycloalkyls and 3- to 14-membered heterocyclines, or pharmaceutically acceptable salts thereof.

[0116] In a preferred embodiment, the present invention is L 1 Covalent bond, -CR 12 R 13-, -CH2O-, -O-, -SO2NH-, and -SO2- are selected from R 12 and R 13 The present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof.

[0117] In a preferred embodiment, the present invention is L 2 The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein the bond is selected from covalent bonds and -CH2-.

[0118] In a preferred embodiment, the present invention is R 1 but [ka] And R 9 , R 10 , R 11 , L 1 The present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein C is as defined herein.

[0119] In a preferred embodiment, the present invention is R 2 This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein the compound is selected from hydrogen and C1-C6 alkyl groups.

[0120] In a preferred embodiment, the present invention is R 3 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein the compound is hydrogen.

[0121] In a preferred embodiment, the present invention is R 6 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein the compound is hydrogen.

[0122] In a preferred embodiment, the present invention is R 8 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein the compound is hydrogen.

[0123] In a preferred embodiment, the present invention is R 12 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein the compound is hydrogen.

[0124] In a preferred embodiment, the present invention is R 5 C1-C6 alkyl and C3-C 10 This specification provides compounds of formula (I) as described herein, selected from cycloalkyl groups, or pharmaceutically acceptable salts thereof.

[0125] In a preferred embodiment, the present invention is R 5 C1-C6 alkyl, halo-C1-C6 alkyl, and C3-C 10 Selected from cycloalkyl groups, C3~C 10 The following are provided: compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein the cycloalkyl group is optionally substituted with one hydroxy substituent.

[0126] In a preferred embodiment, the present invention is R 7 This specification provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, in which the compound is not present.

[0127] In a preferred embodiment, the present invention is R 9 C1-C6 alkyl, halo-C1-C6 alkyl, halo-C1-C6 alkoxy, SF5, C3-C 10 Selected from cycloalkyl, 3- to 14-membered heterocyclyl, and C1-C6 alkoxy-SO2-, and C3-C 10 The cycloalkyl and 3- to 14-membered heterocyclils are optionally substituted with one or two substituents selected from halo-C1 to C6 alkyl and hydroxyl compounds, providing compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof.

[0128] In a preferred embodiment, the present invention is R 9These include halogens, C1-C6 alkyl, halo-C1-C6 alkyl, halo-C1-C6 alkoxy, SF5, C1-C6 alkyl-SO2-, [ka] [ka] and [ka] The present specification provides compounds of formula (I) selected from, or pharmaceutically acceptable salts thereof.

[0129] In a preferred embodiment, the present invention is R 10 The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen, halogens, and C1-C6 alkoxys.

[0130] In a preferred embodiment, the present invention is R 10 The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen, halogens, halo-C1-C6 alkoxys, and C1-C6 alkoxys.

[0131] In a preferred embodiment, the present invention is R 11 This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen and halogens.

[0132] In a preferred embodiment, the present invention is R 14 The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen and halo-C1~C6 alkyl groups.

[0133] In a preferred embodiment, the present invention is R 15This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen and hydroxyl.

[0134] In a preferred embodiment, the present invention is R 16 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein the compound is hydrogen.

[0135] In particularly preferred embodiments, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein A is selected from phenyl, pyridyl, azetidinyl, 2-azaspiro[3.3]heptan-2-yl, 2,6-diazaspiro[3.3]heptanyl, and 2-azaspiro[3.5]nonan-2-yl.

[0136] In particularly preferred embodiments, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein C is selected from phenyl, cyclopropyl, pyridyl, 1,2,4-oxadiazolyl, pyrazinyl, and pyrimidinyl.

[0137] In particularly preferred embodiments, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein D is selected from phenyl, cyclopropyl, pyridyl, 1,2,4-oxadiazolyl, pyrazinyl, and pyrimidinyl.

[0138] In a particularly preferred embodiment, the present invention is R 2 This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein the compound is selected from hydrogen and methyl.

[0139] In a particularly preferred embodiment, the present invention is R 5 This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from ethyl and cyclopropyl.

[0140] In a particularly preferred embodiment, the present invention is R 5The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from ethyl, CF3, and cyclopropyl, and the cyclopropyl is optionally substituted with one hydroxy substituent.

[0141] In a particularly preferred embodiment, the present invention is R 7 This specification provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, in which no such compound exists.

[0142] In a particularly preferred embodiment, the present invention is 9 The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from tert-butyl, CF3, CF3O, SF5, cyclopropyl, azetidinyl, pyrrolidinyl, and methylsulfonyl, and cyclopropyl, azetidinyl, and pyrrolidinyl are optionally substituted with one or two substituents selected from CF3 and hydroxyl.

[0143] In a particularly preferred embodiment, the present invention is R 9 Fluorochloro, tert-butyl, CF3, CF3O, SF5, methylsulfonyl, [ka] [ka] and [ka] The present specification provides compounds of formula (I) selected from, or pharmaceutically acceptable salts thereof.

[0144] In a particularly preferred embodiment, the present invention is R 10 The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen, fluoro, chloro, and methoxy.

[0145] In a particularly preferred embodiment, the present invention is R 10 The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen, fluoro, chloro, CF3, and methoxy.

[0146] In a particularly preferred embodiment, the present invention is R 11 This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein the compound is selected from hydrogen and fluoro.

[0147] In a particularly preferred embodiment, the present invention is R 14 The present specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen and CF3.

[0148] In preferred embodiments, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. A is C6~C 14 Selected from aryls and 3- to 14-membered heterocyclines, B is [ka] (The wavy lines indicate the connection points to the rest of equation (I)) And, C is C6~C 14 Selected from aryls and 5-14 member heteroaryls, L 1 Covalent and -CR 12 R 13 - Selected from, R 1 teeth, [ka] And, R 2 , R 3 , R 4 , R 6 , R 8 , R 11 , R12 , and R 13 These are hydrogen atoms, R 5 C3~C 10 It is a cycloalkyl, R 7 It does not exist, R 9 C1-C6 alkyl, halogen and C3-C 10 Selected from cycloalkyl groups, C3-C 10 The cycloalkyl group is arbitrarily substituted with a halo-C1~C6 alkyl group. R 10 The element is selected from hydrogen and halogens.

[0149] In particularly preferred embodiments, the present invention provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof. A is selected from phenyl, azetidinyl, and 2-azaspiro[3.3]heptan-2-yl, B is [ka] (The wavy lines indicate the connection points to the rest of equation (I)) And, C is selected from phenyl and 1,2,4-oxadiazolyl. L 1 Covalent and -CR 12 R 13 - Selected from, R 1 teeth, [ka] And, R 2 , R 3 , R 4 , R 6 , R 8 , R 11 , R 12 , and R 13 These are hydrogen atoms, R 5It is cyclopropyl, R 7 It does not exist, R 9 It is selected from tert-butyl, fluoro, and cyclopropyl, and cyclopropyl is substituted with CF3. R 10 It is selected from hydrogen and fluorocarbon.

[0150] In a preferred embodiment, the present invention is such that A is C6~C 14 The present invention provides compounds of formula (I) as described herein, selected from aryls and 3- to 14-membered heterocyclines, or pharmaceutically acceptable salts thereof.

[0151] In a preferred embodiment, the present invention relates to C6~C 14 The present invention provides compounds of formula (I) as described herein, selected from aryls and 5- to 14-membered heteroaryls, or pharmaceutically acceptable salts thereof.

[0152] In a preferred embodiment, the present invention is L 1 However, covalent bonding and -CR 12 R 13 - Provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, selected from the above.

[0153] In a preferred embodiment, the present invention is R 2 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein the compound is hydrogen.

[0154] In a preferred embodiment, the present invention is R 11 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein the compound is hydrogen.

[0155] In a preferred embodiment, the present invention is R 5 C3~C 10 This specification provides a cycloalkyl compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof.

[0156] In a preferred embodiment, the present invention is R 9 C1-C6 alkyl, halogen and C3-C 10 Selected from cycloalkyl groups, C3-C 10 This specification provides compounds of formula (I) described herein, in which the cycloalkyl group is substituted with a halo-C1-C6 alkyl group, or pharmaceutically acceptable salts thereof.

[0157] In a preferred embodiment, the present invention is R 10 This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen and halogens.

[0158] In particularly preferred embodiments, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein A is selected from phenyl, azetidinyl, and 2-azaspiro[3.3]heptan-2-yl.

[0159] In particularly preferred embodiments, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein C is selected from phenyl and 1,2,4-oxadiazolyl.

[0160] In a particularly preferred embodiment, the present invention is R 5 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein is cyclopropyl.

[0161] In a particularly preferred embodiment, the present invention is R 9 The present invention provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein is selected from tert-butyl, fluoro, and cyclopropyl, and cyclopropyl is substituted with CF3.

[0162] In a particularly preferred embodiment, the present invention is R 10 This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein the compound is selected from hydrogen and fluoro.

[0163] In a preferred embodiment, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein A is a 3- to 14-membered heterocycline.

[0164] In particularly preferred embodiments, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein A is azetidinil.

[0165] In a preferred embodiment, the present invention relates to C6~C 14 The following are provided: compounds of formula (I) described herein that are aryl, or pharmaceutically acceptable salts thereof.

[0166] In particularly preferred embodiments, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein C is phenyl.

[0167] In a particularly preferred embodiment, the present invention is L 1 The present specification provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, wherein the bond is covalent.

[0168] In a preferred embodiment, the present invention is R 9 C3-C3 is substituted with a halo-C1-C6 alkyl group. 10 This specification provides a cycloalkyl compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof.

[0169] In a particularly preferred embodiment, the present invention is R 9 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein is a cyclopropyl substituted with CF3.

[0170] In a particularly preferred embodiment, the present invention is R 10 This specification provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein the compound is hydrogen.

[0171] In particularly preferred embodiments, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is of formula (II): [ka] (In the formula, A, R 1 , R 2 , R 3 and R 4 (as defined herein) It is a compound of [the compound].

[0172] In one embodiment, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein A is selected from phenyl, cyclobutyl, 1-bicyclo[1.1.1]pentanyl, norbornanyl, 1-bicyclo[2.2.2]octanyl, pyridyl, pyrimidinyl, pyridadinyl, pyrazinyl, azetidinyl, pyrrolidinyl, 5-azaspiro[2.5]octan-5-yl, piperidyl, 3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl, 2-azaspiro[3.3]heptan-2-yl, 2,6-diazaspiro[3.3]heptanyl, and 2-azaspiro[3.5]nonan-2-yl.

[0173] In one embodiment, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein B is selected from pyrazolyl, imidazolyl, triazolyl, pyridyl, oxazolyl, 4,5,6,7-tetrahydroindazole-2-yl, and 6,7-dihydro-4H-pyrano[4,3-c]pyrazole-2-yl.

[0174] In one embodiment, the present invention provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, wherein C is selected from phenyl, cyclopropyl, cyclohexyl, 1,2,4-triazolyl, thiazolyl, pyridyl, 1,2,4-oxadiazolyl; 1,3,4-oxadiazolyl, pyrazolyl, pyrazinyl, pyridadinyl, benzofurazan-4-yl, tetrazolyl, isoxazolyl, pyrimidinyl, morpholinyl, 1,2-dihydropyridiin, piperidyl, pyrrolidinyl, and thietanyl.

[0175] In one embodiment, the present invention is R 1 but, [ka] 2,2,2-trifluoro-1,1-dimethylethoxy, 2,2,2-trifluoroethoxy, C1~C6 alkyl-SO2NH-, C3~C 10 Selected from cycloalkyl-C1~C6alkyl-S(O)2-, C1~C6alkyl-SO2-, halo-C1~C6alkyl-S(O)2-, (C1~C6alkyl)2N-SO2-, halo-C1~C6alkyl-C(O)-, R 9 , R 10 , R 11 , L 1 The present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein C is as defined herein.

[0176] In one embodiment, the present invention is R 2 The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen, fluoro, methyl, CF3, and oxetanyl.

[0177] In one embodiment, the present invention is R 3 This specification provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein the compound is selected from hydrogen and fluoro.

[0178] In one embodiment, the present invention is R5 The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen, fluoro, chloro, cyano, methyl, ethyl, methoxy, CF3, cyclopropyl, cyclobutyl, and azetidinyl, and the cyclopropyl and cyclobutyl are optionally substituted with one or more methyl substituents.

[0179] In one embodiment, the present invention is R 9 Hydrogen, methyl, tert-butyl, 2,2-dimethylpropyl, methoxy, CF3, difluoroethyl, 1,1-difluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trifluoroethoxy, difluoromethoxy, CF3O, (1,1,1-trifluoropropane-2-yl)oxy), fluoro, cyano, SF5, cyclopropyl, cyclopropyl-CH2-, oxetanyl, azetidinyl, pyrrolidinyl, phenyl, methylsulfonyl, 2-neopentylsulfonyl, amino, carboxy, 2-methylpropanoic acid, 2,2-di The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, selected from methylpropanoic acid, methoxycarbonyl, methyl-2,2-dimethylpropanoate, methyl-2-methylpropanoate, NH2SO2-, carbamoyl, C1-C6 alkyl-C(O)NH-, halo-C1-C6 alkyl-NHC(O)-, and oxo, wherein cyclopropyl, phenyl, oxetanyl, azetidinyl, and pyrrolidinyl are optionally substituted with one or two substituents selected from CF3, morpholinyl, halogen, and hydroxyl.

[0180] In one embodiment, the present invention is 10 The present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein is selected from hydrogen, fluoro, chloro, cyano, methyl, methoxy, CF3, 2,2,2-trifluoroethyl, and oxo.

[0181] In preferred embodiments, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. X is CR 8 And, A is a 3- to 14-member heterocycline. B is [ka] (The wavy lines indicate the connection points to the rest of equation (I)) And, C is C6~C 14 It is Ariel, D is C3~C 10 It is a cycloalkyl, L 1 It is a covalent bond, L 2 It is a covalent bond, R 1 teeth, [ka] And, R 2 , R 3 , R 4 , R 6 , R 8 , R 10 , R 11 , R 15 , R 16 It is all hydrogen, R 5 C3~C 10 It is a cycloalkyl, R 7 It does not exist, R 9 teeth, [ka] And, R 14 These are halo-C1~C6 alkyl groups.

[0182] In particularly preferred embodiments, the present invention provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof. X is CR 8 And, A is azetidinyl, B is [ka] (The wavy lines indicate the connection points to the rest of equation (I)) And, C is phenyl, D is cyclopropyl, L 1 It is a covalent bond, L 2 It is a covalent bond, R 1 teeth, [ka] And, R 2 , R 3 , R 4 , R 6 , R 8 , R 10 , R 11 , R 15 , R 16 It is all hydrogen, R 5 It is cyclopropyl, R 7 It does not exist, R 9 teeth, [ka] And, R 14 This is CF3.

[0183] In preferred embodiments, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. X is CR 8 And, A is a 3- to 14-member heterocycline. B is [ka] And, C is a 5-14 member heteroaryl, L 1 It is -CH2-, R 1 ~R 8 This is defined herein.

[0184] In preferred embodiments, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof. X is CR 8 And, A is a 3- to 14-member heterocycline. B is [ka] And, C is a 5- to 14-membered heteroaryl, L 1 It is -CH2-, R 5 C3~C 10 It is a cycloalkyl, R 6 It is hydrogen, R 7 It does not exist, R 1 ~R 4 and R 8 This is defined herein.

[0185] In particularly preferred embodiments, the present invention provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof. X is CR 8 And, A is 2-azaspiro[3.3]heptane, B is [ka] And, C is a 6-membered heteroaryl, L 1 It is -CH2-, R 1 ~R 8 This is defined herein.

[0186] In particularly preferred embodiments, the present invention provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof. X is CR 8 And, A is 2-azaspiro[3.3]heptane, B is [ka] And, C is a 6-membered heteroaryl, L 1 It is -CH2-, R 5 It is cyclopropyl, R 6 It is hydrogen, R 7 It does not exist, R 1 ~R 4 and R 8 This is defined herein.

[0187] In one embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)azetidine-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(3-((1-(trifluoromethyl)cyclopropyl)methyl)-1,2,4-oxadiazole-5-yl)azetidine-1-yl)methanone; (4-(5-(tert-butyl)-1,2,4-oxadiazole-3-yl)phenyl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (4-(5-(tert-butyl)-1,2,4-oxadiazole-3-yl)phenyl)(6-(3-(trifluoromethyl)-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-[3-(trifluoromethyl)pyrazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(4-chloropyrazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(4-cyclopropylpyrazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; 1-[2-[4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)benzoyl]-2-azaspiro[3,3]heptan-6-yl]pyrazole-3-carbonitriel; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-[3-(1-methylcyclopropyl)pyrazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-[5-(1-methylcyclopropyl)pyrazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(4-methoxypyrazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(4,5,6,7-tetrahydroindazole-2-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(3-methoxypyrazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(6,7-dihydro-4H-pyrano[4,3-c]pyrazole-2-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(4-fluoropyrazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-[5-(trifluoromethyl)pyrazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(5-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(6,7-dihydro-4H-pyrano[4,3-c]pyrazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(5-methoxypyrazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; 1-[2-[4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)benzoyl]-2-azaspiro[3,3]heptan-6-yl]-1,2,4-triazole-3-carbonitriel; 1-[2-[4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)benzoyl]-2-azaspiro[3,3]heptan-6-yl]pyrazole-4-carbonitriel; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(4,5,6,7-tetrahydroindazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(6-methyl-3-pyridyl)-2-azaspiro[3,3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[5-methyl-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-methyl-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[5-fluoro-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[6-methyl-5-[[1-(trifluoromethyl)cyclopropyl]methoxy]pyrazine-2-yl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-fluoro-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[5-fluoro-6-[(1-methylcyclopropyl)methoxy]-3-pyridyl]methanone; [[6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-fluoro-6-[(1-methylcyclopropyl)methoxy]-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[2-[[1-(trifluoromethyl)cyclopropyl]methoxy]pyrimidine-5-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[5-methyl-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]pyridazine-3-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[4-(trifluoromethoxy)phenyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[4-(1-morpholinocyclopropyl)phenyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[4-(1,1-difluoroethyl)phenyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[3-fluoro-4-(trifluoromethoxy)phenyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[4-(2,2,2-trifluoroethyl)phenyl]azetidine-1-yl]methanone; [3-(4-cyclopropyl-2-fluorophenyl)azetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; 5-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]azetidine-3-yl]-2-(trifluoromethoxy)benzonitrile; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-methoxy-4-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[2-fluoro-4-(trifluoromethoxy)phenoxy]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[4-(trifluoromethyl)phenoxy]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-(4-tert-butylphenyl)azetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [6-(2-chloro-4-fluorophenoxy)-2-azaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-(3-fluoro-5-(trifluoromethyl)phenoxy)-2-azaspiro[3.3]heptan-2-yl)methanone; 2-[[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]oxy]-5-(trifluoromethoxy)benzonitrile; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[[2-fluoro-4-(pentafluoro-λ 6 -Sulfanyl)phenyl]methoxy]azetidine-1-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-(3,4-difluorobenzyl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((6-(trifluoromethyl)pyrazine-2-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-2-pyridyl]oxy]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-chloro-4-(trifluoromethoxy)phenyl]azetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[4-(trifluoromethoxy)phenoxy]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[2-(trifluoromethyl)pyrimidine-4-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((6-(difluoromethoxy)pyridine-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[6-(trifluoromethyl)pyrimidine-4-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[4-(trifluoromethyl)pyrimidine-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-(2,4-difluorophenoxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((6-methoxypyridine-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((2-(trifluoromethyl)pyrimidine-5-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[6-(trifluoromethyl)pyridazine-3-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((5-fluoropyridine-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (4-(5-(tert-butyl)-1,2,4-oxadiazole-3-yl)phenyl)(6-(4-cyclopropyl-1H-imidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(2,2,2-trifluoroethoxy)-2-azaspiro[3.3]heptan-2-yl]methanone; 4-[[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]oxy]-1-methylpyridine-2-one; [6-(5-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(3,4-difluorophenoxy)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-chloro-4-(trifluoromethoxy)phenyl]azetidine-1-yl]-[6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[5-(trifluoromethyl)pyrazine-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-(trifluoromethoxy)benzyl)oxy)azetidine-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-(trifluoromethyl)benzyl)oxy)azetidine-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((2-fluoro-5-(trifluoromethyl)benzyl)oxy)azetidine-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((3-fluoro-4-(trifluoromethyl)benzyl)oxy)azetidine-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((2-fluoro-4-(trifluoromethoxy)benzyl)oxy)azetidine-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((3-fluoro-5-(trifluoromethyl)benzyl)oxy)azetidine-1-yl)methanone; (3-((2-chloro-4-fluorobenzyl)oxy)azetidine-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-fluoro-2-(trifluoromethyl)benzyl)oxy)azetidine-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-(2,5-difluorophenoxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((6-(trifluoromethyl)pyridine-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((5-(trifluoromethyl)pyridine-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-((5-chloropyridine-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-((6-chloropyridine-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [3-[2-chloro-4-(trifluoromethoxy)phenyl]azetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[3,5-difluoro-4-(trifluoromethoxy)phenyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[2-fluoro-4-(trifluoromethoxy)phenyl]azetidine-1-yl]methanone; [3-(2-tert-butylthiazole-4-yl)azetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[4-[5-(2,2-dimethylpropyl)-1,2,4-oxadiazole-3-yl]phenyl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azapiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-[2-fluoro-4-(trifluoromethyl)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(3-cyclobutyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[rac-(3aR,6aS)-5-(2-chloro-4-fluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[2-[4-(difluoromethoxy)phenyl]ethinyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azapiro[3,3]heptan-2-yl]-[rac-(3aR,6aS)-5-(2-chloro-4-fluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; (3-(2-chloro-3-cyclopropylphenoxy)azetidine-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (3-(4-chloro-3-cyclopropylphenoxy)azetidine-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(2-fluoro-4-(trifluoromethyl)phenoxy)azetidine-1-yl)methanone; (3-(2-chloro-4-methylphenoxy)azetidine-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(2,4-dichlorophenoxy)azetidine-1-yl)methanone; (3-(4-chloro-2-fluorophenoxy)azetidine-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (3-((2-chloro-6-methylpyridine-3-yl)oxy)azetidine-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[3-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[4-(pentafluoro-λ 6 -Sulfanyl)phenyl]methoxy]azetidine-1-yl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[2-fluoro-4-(pentafluoro-λ 6 -Sulfanyl)phenyl]methoxy]azetidine-1-yl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[4-methyl-3-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[2-[2-(difluoromethyl)phenyl]ethynyl]azetidine-1-yl]methanone; [3-[(4-chloro-2-fluorophenyl)methoxy]azetidine-1-yl]-[6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[(2-chloro-4-fluorophenyl)methoxy]azetidine-1-yl]-[6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[(2,4-difluorophenyl)methoxy]azetidine-1-yl]methanone; 4-[[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]-2-azaspiro[3,3]heptan-6-yl]oxy]-3-fluorobenzonitrile; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azapiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-[4-(difluoromethoxy)-2-fluorophenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azapiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-[4-(trifluoromethyl)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; 2-[[rac-(3aS,6aR)-2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-5-yl]oxy]-5-(trifluoromethyl)benzonitrile; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azapiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-[3-chloro-4-(trifluoromethyl)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azapiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-[2-methoxy-4-(trifluoromethyl)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azapiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-[3-fluoro-4-(trifluoromethyl)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; 5-[[rac-(3aS,6aR)-2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-5-yl]oxy]-2-(trifluoromethyl)benzonitrile; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-(3,4-difluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azapiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-[4-fluoro-3-(trifluoromethyl)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-(2,4-difluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azapiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-2-methoxyphenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-2-methylsulfonylphenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-(2,4,6-trifluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azapiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-3-methylphenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azapiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-3-chlorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; 2-Fluoro-5-[[rac-(3aS,6aR)-2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-5-yl]oxy]benzonitrile; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4,5-difluoro-2-methylphenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; 5-Fluoro-2-[[rac-(3aS,6aR)-2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-5-yl]oxy]benzonitrile; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azapiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-3-methylsulfonylphenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azapiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-3-methoxyphenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azapiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-[2,4-difluoro-5-(trifluoromethyl)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azapiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-[4-fluoro-3-(trifluoromethoxy)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azapiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-[4-(trifluoromethoxy)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azapiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-[3-fluoro-4-(trifluoromethoxy)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[[5-(trifluoromethyl)-3-pyridyl]methoxy]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[2-methyl-3-[[4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3[2-[2-(difluoromethyl)phenyl]ethynyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazole-3-yl]azetidine-1-yl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazole-3-yl]azetidine-1-yl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-methyl-6-[(1-methylcyclopropyl)methoxy]-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[5-methyl-6-[(1-methylcyclopropyl)methoxy]-3-pyridyl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[4-(2,2,2-trifluoroethoxy)pyrazole-1-yl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazole-2-yl]azetidine-1-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(4-methylpyrazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [6-(4-methylpyrazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[5-methyl-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(3-methylpyrazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[8-[[1-(trifluoromethyl)cyclopropyl]methoxy]-5-azaspiro[2.5]octane-5-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3,3-difluoro-4-[[1-(trifluoromethyl)cyclopropyl]methoxy]-1-piperidyl]methanone; [6-(3-cyclopropylpyrazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[5-methyl-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone; [6-(3-cyclopropylpyrazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[5-methyl-6-(2,2,2-trifluoro-1,1-dimethylethoxy)-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[5-(trifluoromethyl)-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[5-(oxetan-3-yl)-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[4-[[1-(trifluoromethyl)cyclopropyl]methoxymethyl]-1-bicyclo[2.2.2]octanyl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(3-ethyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(4-ethylimidazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-[4-(trifluoromethyl)imidazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(4-chloroimidazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; 1-[2-[4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)benzoyl]-2-azaspiro[3,3]heptan-6-yl]imidazole-4-carbonitriel; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[4-[[1-(trifluoromethyl)cyclopropyl]methoxymethyl]norbornan-1-yl]methanone; [3-(5-tert-butyl-1,2,4-oxadiazole-3-yl)-1-bicyclo[1.1.1]pentanyl]-[6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-(5-tert-butyl-1,2,4-oxadiazole-3-yl)-1-bicyclo[1.1.1]pentanyl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[1-[1-(trifluoromethyl)cyclopropyl]triazole-4-yl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[4-(2,2,2-trifluoroethoxy)pyrazole-1-yl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazole-5-yl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[1-[3-(trifluoromethyl)oxetane-3-yl]triazole-4-yl]azetidine-1-yl]methanone; [4-(5-tert-butyl-1,3,4-oxadiazole-2-yl)phenyl]-[6-(3-chloro-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,3,4-oxadiazole-2-yl)phenyl]-[6-(3-cyclopropylpyrazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [4-(1-tert-butylpyrazole-4-yl)phenyl]-[6-(3-chloro-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(3-cyclopropylpyrazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(3-chloro-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[[1-(trifluoromethyl)cyclopropyl]methoxymethyl]cyclobutyl]methanone; [6-(3-cyclopropylpyrazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[5-methyl-6-(2,2,2-trifluoro-1,1-dimethylethoxy)-3-pyridyl]methanone; [6-(3-chloro-1,2,4-triazol-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[5-methyl-6-(2,2,2-trifluoro-1,1-dimethylethoxy)-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[[1-(trifluoromethyl)cyclopropyl]methoxy]cyclobutyl]methanone; (6-(3-(azetidine-1-yl)-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-(trifluoromethyl)benzyl)oxy)azetidine-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-4-yl)-2-azapiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-(2-chloro-4-fluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(2-cyclopropyloxazol-5-yl)-6-hydroxy-2-azaspiro[3,3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(5-cyclopropylpyrazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [3-(1-tert-butylpyrazole-4-yl)azetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[3-methyl-4-(trifluoromethoxy)phenyl]azetidine-1-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-cyclopropylphenoxy)azetidine-1-yl)methanone; [6-(3-cyclobutyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; (3-((3-chloro-4-cyclopropylpyridine-2-yl)oxy)azetidine-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(3-ethyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(3-cyclopropyl-4-(trifluoromethyl)phenoxy)azetidine-1-yl)methanone; 5-Cyclopropyl-2-((1-(6-(3-Cyclopropyl-1H-1,2,4-Triazole-1-yl)-2-Azaspiro[3.3]Heptan-2-Carbonyl)Azetidine-3-yl)Oxy)Benzonitrile; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[2-fluoro-4-(trifluoromethyl)benzyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-cyclopropyl-2-fluorophenoxy)azetidine-1-yl)methanone; 2-Cyclopropyl-6-((1-(6-(3-Cyclopropyl-1H-1,2,4-triazole-1-yl)-2-Azaspiro[3.3]heptan-2-carbonyl)azetidine-3-yl)oxy)benzonitrile; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(3-mesylbenzyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)pyrazine-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; Methyl 3-[3-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]azetidine-3-yl]oxyphenyl]-2,2-dimethylpropanoate; N-[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]-3-(trifluoromethyl)benzenesulfonamide; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]-2-yl]-[6-[[4-fluoro-2-(trifluoromethyl)phenyl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [4-[(R)-(3-cyclopropyl-1,2,4-oxadiazole-5-yl)-(4-fluorophenyl)methyl]-1-piperidyl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(3-cyclopropyl-2-fluorophenoxy)azetidine-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; Methyl 2-[3-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]azetidine-3-yl]oxyphenyl]-2-methylpropanoate; (6-(2-chloro-4-fluorobenzyl)-2,6-diazaspiro[3.3]heptan-2-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-(trifluoromethyl)phenoxy)azetidine-1-yl)methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(3-isopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-cyclopropyl-3-fluoropyridine-2-yl)oxy)azetidine-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(4-mesylbenzyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[6-[3-hydroxy-3-(trifluoromethyl)azetidine-1-yl]-3-pyridyl]azetidine-1-yl]methanone; (4-((3-cyclopropyl-1,2,4-oxadiazole-5-yl)(4-fluorophenyl)methyl)piperidine-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((6-cyclopropyl-2-fluoropyridine-3-yl)oxy)azetidine-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[3-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [3-[(5-cyclopropyl-2-pyridyl)oxy]azetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((4-fluoro-2-(trifluoromethyl)phenyl)sulfonyl)-2,6-diazaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[6-[3-hydroxy-3-(trifluoromethyl)pyrrolidino]-3-pyridyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(3,5-difluorophenyl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[6-[(3R)-3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-yl]methanone; N-[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]-2,2-dimethyl-propane-1-sulfonamide; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[6-[(3S)-3-hydroxy-3-(trifluoromethyl)pyrrolidino]-3-pyridyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(5-fluoro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(4-methylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(2-methoxy-3-(trifluoromethyl)phenoxy)azetidine-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(3-cyclopropyl-4-fluorophenoxy)azetidine-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(3,5-difluorobenzyl)-2,6-diazaspiro[3.3]heptan-2-yl]methanone; (3-(2-chloro-3-(trifluoromethyl)phenoxy)azetidine-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; (2-Cyclohexylsulfonyl-2,6-diazaspiro[3.3]heptan-6-yl)-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[4-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[3-fluoro-5-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [4-[(S)-(3-cyclopropyl-1,2,4-oxadiazole-5-yl)-(4-fluorophenyl)methyl]-1-piperidyl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-((2-chloro-4-fluorophenyl)sulfonyl)-2,6-diazaspiro[3.3]heptan-2-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; 2-[[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methyl]methyl benzoate; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[4-(trifluoromethoxy)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(2,4-difluorophenyl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[3-(trifluoromethoxy)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(2,4-difluorobenzyl)-2,6-diazaspiro[3.3]heptan-2-yl]methanone; (3-((4-chloro-5-cyclopropylpyridine-3-yl)oxy)azetidine-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[4-fluoro-3-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-(2-piperidinosulfonyl-2,6-diazaspiro[3.3]heptan-6-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-(4-fluoro-2-mesylphenoxy)-2-azaspiro[3.5]nonan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-(2-neopentylsulfonyl-2,6-diazaspiro[3.3]heptan-6-yl)methanone; 2-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzonitrile; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(2-fluoro-4-methylphenoxy)azetidine-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(2,4,6-trifluorophenyl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [2-[(2-chloro-3-pyridyl)sulfonyl]-2,6-diazaspiro[3.3]heptan-6-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [2-(cyclohexylmethylsulfonyl)-2,6-diazaspiro[3.3]heptan-6-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(3-methoxyphenyl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; N-[[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]azetidine-3-yl]methyl]-3-(trifluoromethyl)benzenesulfonamide; 6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-N-[[1-(trifluoromethyl)cyclopropyl]methyl]-2,6-diazaspiro[3.3]heptan-2-sulfonamide; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((6-(trifluoromethyl)pyridazine-3-yl)oxy)azetidine-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-((1,1,1-trifluoropropan-2-yl)oxy)-1H-pyrazole-1-yl)azetidine-1-yl)methanone; (2-Benzofurazan-4-ylsulfonyl-2,6-diazaspiro[3.3]heptan-6-yl)-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(2-methoxyphenyl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[4-[1-(2H-tetrazole-5-yl)cyclopropyl]phenyl]azetidine-1-yl]methanone; N-[[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]-4-piperidyl]methyl]-4-(trifluoromethyl)benzenesulfonamide; (3-((6-chloro-5-cyclopropylpyridine-3-yl)oxy)azetidine-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[[6-(trifluoromethyl)-3-pyridyl]sulfonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methanone; 6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-N-(4-fluorobenzyl)-2,6-diazaspiro[3.3]heptan-2-sulfonamide; 2-[[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methyl]benzenesulfonamide; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(3,5-difluoro-2-pyridyl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; N-[[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]-4-piperidyl]methyl]-4-(trifluoromethoxy)benzenesulfonamide; 6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-N-[1-(trifluoromethyl)cyclopropyl]-2,6-diazaspiro[3.3]heptan-2-sulfonamide; 4-(1-(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl)azetidine-3-yl)-1-(2,2,2-trifluoroethyl)pyridine-2(1H)-one; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[[2-fluoro-4-(trifluoromethyl)benzyl]amino]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[[4-(trifluoromethyl)-3-pyridyl]sulfonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methanone; 2-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]methyl benzoate; (2-benzylsulfonyl-2,6-diazaspiro[3.3]heptan-6-yl)-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-(2-fluoro-4-mesyl-benzyl)oxyazetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[6-(trifluoromethyl)pyridazine-3-yl]amino]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[[5-(trifluoromethyl)-3-pyridyl]sulfonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methanone; 6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-N-(1-methylcyclopropyl)-2,6-diazaspiro[3.3]heptan-2-sulfonamide; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((6-(trifluoromethyl)pyridine-3-yl)oxy)azetidine-1-yl)methanone; 4-Chloro-N-[[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]-4-piperidyl]methyl]benzenesulfonamide; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[2-(4-fluorophenyl)ethylsulfonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(3,4-difluorophenyl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((2-cyclopropylpyrimidine-4-yl)oxy)azetidine-1-yl)methanone; (6-(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)(4-fluoro-2-(trifluoromethyl)phenyl)methanone; N-[[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]azetidine-3-yl]methyl]-4-(trifluoromethyl)benzenesulfonamide; N-[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]-1-(trifluoromethyl)cyclopropanecarboxamide; [2-[(4-chloro-3-pyridyl)sulfonyl]-2,6-diazaspiro[3.3]heptan-6-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 2-[3-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]azetidine-3-yl]oxyphenyl]-2-methylpropanoic acid; [3-(6-cyclopropylpyridazin-3-yl)oxyazetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(3,5-dimethylisoxazole-4-yl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(4-methoxyphenyl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((2-(trifluoromethyl)pyrimidine-4-yl)oxy)azetidine-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-(2-pyrrolidinosulfonyl-2,6-diazaspiro[3.3]heptan-6-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((6-(trifluoromethyl)pyrimidine-4-yl)oxy)azetidine-1-yl)methanone; [2-[(6-chloro-2-pyridyl)sulfonyl]-2,6-diazaspiro[3.3]heptan-6-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 3-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzonitrile; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(1-methylcyclopropyl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(5-(2,4-difluorophenyl)-4H-1,2,4-triazole-3-yl)azetidine-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(4-fluoro-2-methoxyphenyl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; (2S)-2-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]-4-piperidyl]-2-(4-fluorophenyl)acetamide; (6-(2-chloro-4-fluorobenzoyl)-2,6-diazaspiro[3.3]heptan-2-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; 4-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]azetidine-3-yl]benzenesulfonamide; 3-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]-4-fluorobenzamide; N-[4-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]phenyl]acetamide; [2-(cyclopropylmethylsulfonyl)-2,6-diazaspiro[3.3]heptan-6-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[[2-(trifluoromethyl)-3-pyridyl]sulfonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methanone; 4-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzamide; 3-[3-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]azetidine-3-yl]oxyphenyl]-2,2-dimethylpropanoic acid; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(5-methylisoxazole-4-yl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; (2R)-2-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]-4-piperidyl]-2-(4-fluorophenyl)acetamide; N-[[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]azetidine-3-yl]methyl]-4-fluoro-2-(trifluoromethyl)benzenesulfonamide; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((6-(trifluoromethyl)pyrazine-2-yl)oxy)azetidine-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-(2-trifuryl-2,6-diazaspiro[3.3]heptan-6-yl)methanone; 2-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]-4-piperidyl]-2-(4-fluorophenyl)acetamide; (2S)-2-[4-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]piperazino]-2-(4-fluorophenyl)acetamide; [3-[[4-(pentafluoro-16-sulfanyl)phenyl]methoxy]azetidine-1-yl]-[6-[4-(trifluoromethyl)imidazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; 4-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzonitrile; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[(2-methoxy-3-pyridyl)sulfonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [2-(2-aminopyrimidine-5-yl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 2-[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]-N-methyl-2-phenylacetamide; 1-(1-(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl)azetidine-3-yl)-N-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carboxamide; 2-[[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methyl]benzoic acid; 6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-N,N-dimethyl-2,6-diazaspiro[3.3]heptan-2-sulfonamide; [6-(4-methylimidazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[[4-(pentafluoro-16-sulfanyl)phenyl]methoxy]azetidine-1-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-(trifluoromethyl)pyrimidine-2-yl)oxy)azetidine-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(3-pyridylsulfonyl)-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-(2-morpholinosulfonyl-2,6-diazaspiro[3.3]heptan-6-yl)methanone; 3-[[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]-4-piperidyl]methyl]-4-fluorobenzenesulfonamide; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-(2-propylsulfonyl-2,6-diazaspiro[3.3]heptan-6-yl)methanone; N-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]-4-piperidyl]-4-(trifluoromethyl)benzenesulfonamide; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[4-(trifluoromethyl)pyridazine-3-yl]oxyazetidine-1-yl]methanone; 2-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzamide; 4-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzoic acid; N-[[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]-4-piperidyl]methyl]benzenesulfonamide; (2R)-2-[4-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]piperazino]-2-(4-fluorophenyl)acetamide; 3-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]-4-fluorobenzoic acid; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(5-ethyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(2,2,2-trifluoroethylsulfonyl)-2,6-diazaspiro[3.3]heptan-6-yl]methanone; (2S)-2-[4-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]piperazino]-2-(4-fluorophenyl)-N-methylacetamide; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(1-methylpyrazole-4-yl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; 2-[4-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]piperazino]-2-(4-fluorophenyl)acetamide; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(5-(cyclopropylmethyl)-4H-1,2,4-triazol-3-yl)azetidine-1-yl)methanone; 2-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]-N-methyl-benzamide; (2R)-2-[4-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]piperazino]-2-(4-fluorophenyl)-N-methylacetamide; N-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]-4-piperidyl]-4-fluorobenzenesulfonamide; 1-[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]-2,2,2-trifluoro-ethanone; 2-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]-2,6-diazaspiro[3,3]heptan-2-yl]sulfonyl]benzoic acid; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(1,1-diketothietan-3-yl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; 2-[4-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]piperazino]-2-(4-fluorophenyl)-N-methylacetamide; [3-[4-(4-chloro-2-methylsulfonylphenyl)phenyl]azetidine-1-yl]-[6-(triazole-2-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [3-[4-(4-chloro-2-methylsulfonylphenyl)phenyl]azetidine-1-yl]-[6-(triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(4-fluorophenyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[6-[2-(trifluoromethyl)pyrimidine-5-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[4-(trifluoromethylsulfonyl)phenyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(4-methylsulfonylphenyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-chloro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(5-fluoro-3-pyridyl)-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [3-[4-[3-(2,2-dimethylpropyl)triazole-4-yl]phenyl]azetidine-1-yl]-[6-(5-fluoro-3-pyridyl)-2,6-diazaspiro[3,3]heptan-2-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[6-(5-fluoro-3-pyridyl)-2,6-diazaspiro[3,3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[(6S)-6-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[(6R)-6-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[4-fluoro-2-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-(5-cyclopropyl-3-methylpyrazole-1-yl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-(5-cyclopropyl-3-methylpyrazole-1-yl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-(3,5-dimethylpyrazole-1-yl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(1H-pyrazolo[4,3-b]pyridine-5-ylmethyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-methylsulfonyl-5-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[(6S)-6-[[3-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[(6R)-6-[[3-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[(6S)-6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[(6R)-6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [6-[(4-cyclopropylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; 5-[[2-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]-2-(trifluoromethyl)benzonitrile; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[6-(5-fluoro-3-pyridyl)-2-azaspiro[3,3]heptan-2-yl]methanone; [6-[(5-chloro-3-fluoro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; 4-[[2-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]-2-(trifluoromethyl)benzonitrile; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[7-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2,7-diazaspiro[3.4]octan-2-yl]methanone; 3-[[2-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]-5-(trifluoromethyl)benzonitrile; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3,3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]-[3-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-3-pyridyl]azetidine-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]-[3-[6-[(3R)-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(4-dimethylphosphorylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-dimethylphosphorylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-dimethylphosphoryl-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(5-dimethylphosphoryl-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(4-dimethylphosphorylphenyl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(5-fluoro-3-pyridyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[6-(trifluoromethoxy)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[[6-(trifluoromethyl)-3-pyridyl]methyl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-(1H-pyrazolo[4,3-b]pyridine-5-ylmethyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[(5-cyclopropyl-4H-1,2,4-triazole-3-yl)methyl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-methylsulfonyl-3-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-(4-chloro-2-methylsulfonylphenyl)-3-pyridyl]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; 5-[[(6S)-2-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.4]octane-6-yl]oxy]-2-(trifluoromethyl)pyridine-4-carbonitriel; [6-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3.4]octan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [6-[(5-fluoro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[7-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[[2-methoxy-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]-[3-[4-[5-[(1-methylcyclopropyl)methyl]-4H-1,2,4-triazole-3-yl]phenyl]azetidine-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[[1-(trifluoromethyl)cyclopropyl]methylamino]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonylphenyl)phenyl]azetidine-1-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]-[3-[6-[(3S)-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidine-1-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]-[3-[[4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidine-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)-2-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; N-[2-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]-3-(trifluoromethyl)benzenesulfonamide; [6-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(2-fluoro-4-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-chloro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[6-(trifluoromethyl)pyridazin-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(trifluoromethyl)pyrimidine-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(3-fluoro-5-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [3-[4-(4-chloro-2-methylsulfonylphenyl)phenyl]azetidine-1-yl]-[6-(1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[(4-dimethylphosphorylphenyl)methoxy]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[(4-dimethylphosphorylphenyl)methoxy]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-fluoro-2-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[4-[3-(2,2-dimethylpropyl)triazole-4-yl]phenyl]azetidine-1-yl]-[6-(1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [3-[3-[5-[1-(trifluoromethyl)cyclopropyl]-4H-1,2,4-triazole-3-yl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[5-[1-(trifluoromethyl)cyclopropyl]-4H-1,2,4-triazole-3-yl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; [3-[3-[[[1-(trifluoromethyl)cyclopropyl]amino]methyl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-[[1-(trifluoromethyl)cyclopropyl]methylamino]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-[3-(trifluoromethyl)azetidine-1-yl]-3-pyridyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]methanone; [3-[2-[3-(trifluoromethyl)azetidine-1-yl]pyrimidine-5-yl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]methanone; [3-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-3-pyridyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]methanone; [3-[4-[5-[(1-methylcyclopropyl)methyl]-4H-1,2,4-triazole-3-yl]phenyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]methanone; [3-[6-[(3S)-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]methanone; [3-[6-[(3R)-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]methanone; [3-[6-[(1,1-dioxothietan-3-yl)methylamino]-3-pyridyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]methanone; 2-[4-[1-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3,3]heptan-2-carbonyl]azetidine-3-yl]phenyl]benzamide; [6-[[4-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-(5-cyclopropyl-4H-1,2,4-triazole-3-yl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; [3-[3-(5-cyclopropyl-4H-1,2,4-triazole-3-yl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2,7-diazaspiro[3.4]octan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazole-2-yl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; [3-[3-(5-cyclopropyl-1,3,4-oxadiazole-2-yl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(trifluoromethyl)pyrazine-2-yl]methyl]-2,7-diazaspiro[3.4]octan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[6-(trifluoromethyl)pyridazine-3-yl]methyl]-2,7-diazaspiro[3.4]octan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2,7-diazaspiro[3.4]octan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[[[1-(trifluoromethyl)cyclopropyl]amino]methyl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[[1-(trifluoromethyl)cyclopropyl]methylamino]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[4-[5-[(1-methylcyclopropyl)methyl]-4H-1,2,4-triazole-3-yl]phenyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(5-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[[2-Methoxy-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]methanone; [3-[6-[3-hydroxy-3-(trifluoromethyl)azetidine-1-yl]-3-pyridyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]methanone; [3-[6-(3-hydroxy-3-methylazetidine-1-yl)-3-pyridyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]methanone; 3-(trifluoromethyl)-N-[2-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]benzenesulfonamide; [6-[(4-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(3-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-methylsulfonyl-3-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-methylsulfonyl-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(2-fluoro-4-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(3-fluoro-5-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[[3-(trifluoromethyl)oxetane-3-yl]amino]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[4-[5-[1-(trifluoromethyl)cyclopropyl]-4H-1,2,4-triazole-3-yl]phenyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[4-(5-cyclopropyl-1H-1,2,4-triazole-3-yl)phenyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(3-fluoro-5-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[5-[[1-(trifluoromethyl)cyclopropyl]methylamino]pyrazine-2-yl]azetidine-1-yl]methanone; [3-[4-(5-cyclobutyl-1H-1,2,4-triazole-3-yl)phenyl]azetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[6-(trifluoromethyl)pyridazine-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)pyrazine-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[[3-(trifluoromethyl)-1-bicyclo[1.1.1]pentanyl]sulfonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-fluoro-2-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[6-[(3S)-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[6-[[1-(trifluoromethyl)cyclopropyl]amino]-3-pyridyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[5-[[1-(trifluoromethyl)cyclopropyl]methylamino]-2-pyridyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[2-[3-(trifluoromethyl)azetidine-1-yl]pyrimidine-5-yl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[6-[(3S)-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[2-[(3S)-3-(trifluoromethyl)pyrrolidine-1-yl]pyrimidine-5-yl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[2-[(3R)-3-(trifluoromethyl)pyrrolidine-1-yl]pyrimidine-5-yl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(2-fluoro-4-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[3-(trifluoromethyl)-1-bicyclo[1.1.1]pentanyl]sulfonyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[(3-methylsulfonylphenyl)methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[(4-methylsulfonylphenyl)methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)pyrazine-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(5-methylsulfonyl-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(5-methylsulfonyl-3-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[(3-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]-[3-[6-[[1-(trifluoromethyl)cyclopropyl]amino]-3-pyridyl]azetidine-1-yl]methanone; (2R)-1-[4-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]azetidine-3-yl]phenyl]-4,4-difluoropiperidine-2-carboxamide; (2R)-1-[4-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]azetidine-3-yl]phenyl]-4,4-difluoropiperidine-2-carboxamide; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]-[3-[6-[3-(trifluoromethyl)azetidine-1-yl]-3-pyridyl]azetidine-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[2-[3-(trifluoromethoxy)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[[3-(trifluoromethylsulfonyl)phenyl]methoxy]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[[4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-methylsulfonylphenyl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(3-methylsulfonylphenyl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(2-methylsulfonylphenyl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; 1-[4-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]azetidine-3-yl]phenyl]-4,4-difluoropiperidine-2-carboxamide; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[6-(3-hydroxy-3-methylazetidine-1-yl)-3-pyridyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[6-[(1,1-dioxothiolan-3-yl)amino]-3-pyridyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[4-(3-fluorophenoxy)-1-piperidyl]methanone; [3-(4-cyclobutylphenyl)azetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[2-(2-fluoro-6-methylphenyl)ethyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[(E)-2-(3-fluorophenyl)vinyl]azetidine-1-yl]methanone; Bis[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [7-[[6-(difluoromethoxy)-3-pyridyl]methyl]-2-azaspiro[3.5]nonan-2-yl]-[6-(5-fluoro-3-pyridyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-cyclopropyl-4-(trifluoromethyl)phenoxy]azetidine-1-yl]-[6-(5-fluoro-3-pyridyl)-2-azaspiro[3,3]heptan-2-yl]methanone; [3-[(2-chloro-4-fluorophenyl)methoxy]azetidine-1-yl]-[6-(5-fluoro-3-pyridyl)-2-azaspiro[3,3]heptan-2-yl]methanone; [3-[[2-chloro-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[6-(5-fluoro-3-pyridyl)-2-azaspiro[3,3]heptan-2-yl]methanone; [6-(5-fluoro-3-pyridyl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [7-[(5-fluoro-2-pyridyl)methyl]-2-azaspiro[3.5]nonan-2-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [7-[(5-chloro-2-pyridyl)methyl]-2-azaspiro[3.5]nonan-2-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[[2-Methoxy-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3,3]heptan-2-yl]methanone; [6-[[5-(trifluoromethyl)pyrazine-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3,3]heptan-2-yl]-[3[[4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidine-1-yl]methanone; [7-[[6-(difluoromethoxy)-3-pyridyl]methyl]-2-azaspiro[3.5]nonan-2-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; Bis[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3,3]heptan-2-yl]methanone; [3-[6-[3-(trifluoromethyl)azetidine-1-yl]-3-pyridyl]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3,3]heptan-2-yl]methanone; [6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[6-(trifluoromethyl)-3-pyridyl]oxy]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [3-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-3-pyridyl]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-cyclopropyl-4-(trifluoromethyl)phenoxy]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3,3]heptan-2-yl]methanone; [6-[(3-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(4-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[[2-chloro-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3,3]heptan-2-yl]methanone; [6-[[4-methylsulfonyl-3-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[(2-chloro-4-fluorophenyl)methoxy]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3,3]heptan-2-yl]methanone; [3-[6-(4-isopropyl-N-methyl-anilino)-3-pyridyl]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3,3]heptan-2-yl]methanone; [6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; 2-(trifluoromethyl)-5-[[2-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]benzonitrile; [3-[5-(2,4-dichlorophenyl)-2-pyridyl]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3,3]heptan-2-yl]methanone; [3-[6-(2-chloro-4-methylsulfonylphenyl)-3-pyridyl]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; and [3-[5-(4-chloro-2-fluorophenyl)-2-pyridyl]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3,3]heptan-2-yl]methanone Selected from.

[0188] In preferred embodiments, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-(2-methoxy-4-(trifluoromethyl)benzyl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-(2-fluoro-4-(trifluoromethoxy)phenoxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)azetidine-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-cyclopropylphenoxy)azetidine-1-yl)methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(3-ethyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-(4-(trifluoromethyl)phenoxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(2-chloro-4-fluorophenoxy)-2-azaspiro[3.3]heptan-2-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-(3-fluoro-5-(trifluoromethyl)phenoxy)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)pyrazine-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[[2-fluoro-4-(pentafluoro-16-sulfanyl)phenyl]methoxy]azetidine-1-yl]methanone (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-(3,4-difluorobenzyl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((6-(trifluoromethyl)pyrazine-2-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[2-fluoro-4-(trifluoromethoxy)phenyl]azetidine-1-yl]methanone; N-[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]-3-(trifluoromethyl)benzenesulfonamide; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]-2-yl]-[6-[[4-fluoro-2-(trifluoromethyl)phenyl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((5-(trifluoromethyl)pyridine-2-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(3-fluoro-4-(trifluoromethoxy)phenyl)azetidine-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-(trifluoromethoxy)phenyl)azetidine-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(2-chloro-4-fluorobenzyl)-2,6-diazaspiro[3.3]heptan-2-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-(3,4-difluorophenoxy)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(4-mesylbenzyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[6-[3-hydroxy-3-(trifluoromethyl)azetidine-1-yl]-3-pyridyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[3-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((4-fluoro-2-(trifluoromethyl)phenyl)sulfonyl)-2,6-diazaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[6-[(3R)-3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((2-(trifluoromethyl)pyrimidine-4-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[6-[(3S)-3-hydroxy-3-(trifluoromethyl)pyrrolidino]-3-pyridyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(5-fluoro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((5-(trifluoromethyl)pyrazine-2-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((3-fluoro-5-(trifluoromethyl)benzyl)oxy)azetidine-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((6-(trifluoromethyl)pyridine-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((6-(trifluoromethyl)pyrimidine-4-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-(2,4-difluorophenoxy)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[4-(trifluoromethoxy)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; (4-(5-(tert-butyl)-1,2,4-oxadiazole-3-yl)phenyl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-(4-fluoro-2-mesylphenoxy)-2-azaspiro[3.5]nonan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(5-methyl-6-((1-(trifluoromethyl)cyclopropyl)methoxy)pyridine-3-yl)methanone; and (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(3-((1-(trifluoromethyl)cyclopropyl)methyl)-1,2,4-oxadiazole-5-yl)azetidine-1-yl)methanone Selected from.

[0189] In particularly preferred embodiments, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)azetidine-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-(4-(trifluoromethyl)phenoxy)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)pyrazine-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(4-mesylbenzyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[3-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(5-fluoro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; (4-(5-(tert-butyl)-1,2,4-oxadiazole-3-yl)phenyl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; and (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(3-((1-(trifluoromethyl)cyclopropyl)methyl)-1,2,4-oxadiazole-5-yl)azetidine-1-yl)methanone Selected from.

[0190] In certain embodiments, the present invention provides pharmaceutically acceptable salts of compounds of formula (I) described herein. In even more specific embodiments, the present invention provides compounds of formula (I) described herein as free bases.

[0191] In some embodiments, the compound of formula (I) is isotope-labeled by having one or more atoms within it that are replaced by atoms having different atomic masses or mass numbers. Such isotope-labeled (i.e., radioactively labeled) compounds of formula (I) are considered to be within the scope of this disclosure. Examples of isotopes that can be incorporated into the compound of formula (I) are isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, and iodine, respectively, for example. 2 H, 3 H, 11 C, 13 C, 14 C, 13 N, 15 N, 15 O, 17 O, 18 O, 31 P, 32 P, 35 S, 18 F, 36 Cl, 123 I, and 125 Examples include, but are not limited to, formula (I). Certain isotope-labeled compounds of formula (I), for example, those incorporating radioactive isotopes, are useful for studying the tissue distribution of drugs and / or substrates. Radioactive isotope tritium, i.e., 3 H and carbon-14, that is, 14 C is particularly useful for this purpose, considering its ease of incorporation and immediate detection means. For example, the compound of formula (I) can be concentrated at 1, 2, 5, 10, 25, 50, 75, 90, 95, or 99 percent of a given isotope.

[0192] Heavier isotopes, such as deuterium, 2 Substitution with H, etc., can lead to increased metabolic stability, potentially resulting in specific therapeutic benefits, such as a longer in vivo half-life or a reduced required dosage.

[0193] 11 C, 18 F, 15 O and 13Substitution with positron-emitting isotopes such as 1N may be useful in positron emission tomography (PET) studies to examine the receptor occupancy of a substrate. Compounds of formula (I) labeled with isotope may be prepared by conventional techniques known to those skilled in the art, or by methods similar to those described in the examples below, using appropriate isotope-labeled reagents instead of previously used unlabeled reagents.

[0194] Manufacturing method The compounds of formula (I) of the present invention can be prepared by sequential or convergent synthetic routes. The synthesis of the present invention is shown in the following general scheme. The skills required to perform the reaction and purification of the resulting products are known to those skilled in the art. Substituents and indices used in the following description of the method have the meanings given herein unless otherwise indicated.

[0195] If one of the starting materials, intermediates, or compounds of formula (I) contains one or more functional groups that are unstable or reactive under the reaction conditions of one or more reaction steps, an appropriate protecting group (such as those described in "Protective Groups in Organic Chemistry" by TW Greene and PGMWutts, 5th edition, 2014, John Wiley & Sons, NY) can be introduced before a critical step by applying methods well known in the art. Such protecting groups can be removed at later stages of synthesis using standard methods described in the literature.

[0196] If the starting material or intermediate contains a stereocenter, the compound of formula (I) can be obtained as a mixture of diastereomers or enantiomers, which can be separated by methods well known in the art, such as chiral HPLC, chiral SFC, or chiral crystallization. Racemic compounds can be separated into their counterparts via diastereomer salts, for example, by crystallization with an optically pure acid, or by separating the counterparts by a specific chromatographic method using either a chiral adsorbent or a chiral eluent. It is also possible to separate the starting material and intermediate containing a stereocenter to obtain diastereomerically / enantiomerically enriched starting material and intermediate. When such diastereomerically / enantiomerically enriched starting material and intermediate are used in the synthesis of the compound of formula (I), the respective diastereomerically / enantiomerically enriched compounds of formula (I) are generally obtained.

[0197] Those skilled in the art will recognize that, in the synthesis of compounds of formula (I) (unless otherwise desired), an "orthogonal protection group strategy" can be applied to cleave several protecting groups one at a time without affecting other protecting groups in the molecule. The principle of orthogonal protection is well known in the art and is also described in the literature (e.g., Barany and RBMerrifield, J.Am.Chem.Soc. 1977, 99, 7363; H.Waldmann et al., Angew.Chem.Int.Ed.Engl. 1996, 35, 2056).

[0198] Those skilled in the art will recognize that the order of reactions may vary depending on the reactivity and properties of the intermediates.

[0199] More specifically, the compound of formula (I) can be prepared by the method shown below, the method shown in the examples, or a similar method. Suitable reaction conditions for each reaction step are known to those skilled in the art. For reaction conditions described in the literature that may affect the described reaction, see, for example, the following: Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 2nd Edition, Richard C. Larock, John Wiley & Sons, New York, NY. 1999). The reaction could be carried out readily with or without a solvent. There are no particular restrictions on the properties of the solvent used, as long as it does not adversely affect the reaction or the reagents involved and can dissolve the reagents to at least some extent. The described reaction can occur over a wide range of temperatures, and the exact reaction temperature is not important to the present invention. It is convenient to carry out the described reaction in the temperature range from -78°C to reflux. The time required for the reaction can also vary considerably, depending on many factors, particularly the reaction temperature and the properties of the reagents. However, obtaining the described intermediates and compounds usually takes only 0.5 hours to a few days. The reaction sequence is not limited to the order shown in the scheme, and the order of the reaction steps can be freely changed depending on the starting materials and their respective reactivity.

[0200] If the starting materials or intermediates are not commercially available, or if their synthesis is not documented in the literature, they may be prepared in the same manner as existing procedures for similar analogs, or as outlined in the experimental section.

[0201] The following abbreviations are used in this specification: AcOH = acetic acid, ACN = acetonitrile, Bn = benzyl, BINAP = (2,2'-bis(diphenylphosphin)-1,1'-binaphthyl), Boc = tert-butyloxycarbonyl, CAS RN = Chemical Abstracts Registration Number, Cbz = Benzyloxycarbonyl, Cs2CO3 = Cesium Carbonate, CO = Carbon Monoxide, CuCl = Copper(I) Chloride, CuCN = Copper(I) Cyanide, CuI = Copper(I) Iodide, DABCO = 1,4-Diazabicyclo[2.2.2]octane; Triethylenediamine, DAST = Sulfur (Diethylamino) Trifluoride, DBU = 1,8-Diazabicyclo[5,4,0]undeca-7-ene, DEAD = Diethylazodicarboxylate, DIAD = Diisopropylazodicarboxylate, DIBAL-H = Diisobutylaluminum Hydrogenate, DMAP = 4-Dimethylaminopyridine, DME = Dimethoxyethane, DMEDA = N,N '-dimethylethylenediamine, DMF=N,N-dimethylformamide, DIPEA=N,N-diisopropylethylamine, dppf=1,1-bis(diphenylphosphin)ferrocene, EDC.HCl=N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride, EI=electron shock, ESI=electrospray ionization, siRNA=ethyl acetate, EtOH=ethanol, h=hour, FA=formic acid, H2O=water, H2SO4=sulfuric acid, HATU=1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxidehexafluorophosphate, HBTU=O-benzotriazole-N,N,N',N'-Tetramethyluronium-hexafluorophosphate, HCl = hydrogen chloride, HOBt = 1-hydroxy-1H-benzotriazole, HPLC = high-performance liquid chromatography, iPrMgCl = isopropylmagnesium chloride, I2 = iodine, IPA = 2-propanol, ISP = positive ion spray (mode), ISN = negative ion spray (mode), K2CO3 = potassium carbonate, KHCO3 = potassium bicarbonate, KI = potassium iodide, KOH = potassium hydroxide, K3PO4 = tripotassium phosphate, LiAlH4 or L AH = Lithium aluminum hydride, LiHMDS = Lithium bis(trimethylsilyl)amide, LiOH = Lithium hydroxide, mCPBA = Meta-chloroperbenzoic acid, MgSO4 = Magnesium sulfate, min = minute, mL = milliliter, MPLC = Medium pressure liquid chromatography, MS = Mass spectrum, nBuLi = n-Butyllithium, NaBH3CN = Sodium borohydride cyanohydride, NaH = Sodium hydride, NBS = N-bromosuccinimide, NaHCO3 = Sodium bicarbonate, NaNO2 = Sodium nitrite, NaBH( OAc)3 = Sodium triacetoxyborohydride, NaOH = Sodium hydroxide, Na2CO3 = Sodium carbonate, Na2SO4 = Sodium sulfate, Na2S2O3 = Sodium thiosulfate, NET3 = Triethylamine (TEA), NH4Cl = Ammonium chloride, NMP = N-methyl-2-pyrrolidone, OAc = Acetoxy, T3P = Propylphosphone anhydride, PE = Petroleum ether, PG = Protecting group, Pd-C = Palladium-activated carbon, PdCl2(dppf)-CH2Cl2 = 1,1'-Bis(diphenylphosphin)ferrocene Palladium(II) dichloride dichloromethane complex, Pd2(dba)3=tris(dibenzylideneacetone)dipalladium(0), Pd(OAc)2=palladium(II) acetate, Pd(OH)2=palladium hydroxide, Pd(PPh3)4=tetrakis(triphenylphosphine)palladium(0), PMP=1,2,2,6,6-pentamethylpiperidine, PTSA=p-toluenesulfonic acid, R=any group, RP=reverse phase, RT=room temperature, SFC=supercritical fluid chromatography, S-PHOS=2-dicyclohexylphosphin-2',6'-Dimethoxybiphenyl, TBAI = Tetrabutylammonium Iodine, TEA = Triethylamine, TFA = Trifluoroacetic Acid, THF = Tetrahydrofuran, TMEDA = N,N,N',N'-Tetramethylethylenediamine, TS-TPP = Triphenylphosphine-polymer bond, ZnCl2 = Zinc Chloride, Hal = Halogen, prep-TLC = Preparative Thin-Layer Chromatography.

[0202] The compounds of the present invention, of formula I, in which ring A is an N-linked aliphatic heterocycle, can be prepared by reacting the activated intermediate of formula 2 with a nucleophilic cyclic amine by heating in a solvent such as DMF or CH3CN in the presence of a base such as DIPEA. In some cases, an alternative activated intermediate having a 4-nitrophenyl group was used instead of 1,2,4-triazole (Scheme 1). [ka]

[0203] The activated intermediate 2 can be produced by reacting amine 3 with a coupling agent such as di(1H-1,2,4-triazole-1-yl)methanone in a solvent such as CH2Cl2 in the presence of a base such as DIPEA (Scheme 2). The related 4-nitrophenyl carbonate intermediate can be produced in a similar manner using 4-nitrophenylca carbonochloride. Alternatively, the same strategies as in Schemes 1 and 2 may be used, but the activated intermediate may be constructed on ring A first before coupling with amine 3. [ka]

[0204] Ring B is an N-bonded aromatic heterocycle, and X=CR 8In this case, amine 3 can be produced by reacting a nucleophilic heteroaryl 5 with a appropriately functionalized 2-azaspiro[3.3]heptane building block 4 (Y=leaving group, e.g., OMs, Cl, I, Br) in the presence of a base (e.g., DIPEA, Cs2CO3), followed by deprotection of the protecting group using standard conditions (e.g., using TFA with PG=Boc) (Scheme 3). Typically, a mesylate building block is used (Y=OMs), which can be conveniently produced from a hydroxyl analog by reacting it with MsCl in the presence of a mild base such as Et3N. [ka]

[0205] Alternatively, compounds of formula I in which ring A is an N-linked aliphatic heterocycle can be produced by direct coupling of building blocks 1 and 3 using a coupling agent such as CDI or triphosgene and a base (e.g., TEA, DIPEA) (Scheme 4). Intermediates corresponding to formula I (e.g., 14, 16) can also be prepared in this manner. [ka]

[0206] Alternatively, compounds of formula I in which ring A is carbon-bonded can be produced by coupling a suitable acid with amine 3 (e.g., using a coupling agent (e.g., HATU or T3P, etc.) and a base (e.g., TEA or DIPEA, etc.)) (Scheme 5). Intermediates corresponding to formula I (e.g., 12)) can also be prepared in this manner. [ka]

[0207] Alternatively, X is CR 8Compounds of formula I, in which ring B is an N-bonded aromatic heterocycle, can be produced by reacting a nucleophilic heteroaryl 5 with a appropriately functionalized intermediate 7 (Y = leaving group, e.g., OMs) in the presence of a base (e.g., Cs2CO3, NaOtBu) (Scheme 6). Intermediate 7 can be produced by coupling a suitable hydroxylation building block with ring A as described in Scheme 1 or 4 to produce intermediate 8, and then converting the hydroxyl group to a suitable leaving group (e.g., by mesylation in the presence of MsCl and a base). Alternatively, the hydroxylated intermediate 8 can be directly converted to the compound of formula I using Mitsunobu-type conditions (e.g., PS-PPh3, DIAD in THF) and a nucleophilic heteroaryl 5. [ka]

[0208] Alternatively, X=CR 8 And when ring B is a C-bonded (hetero)aryl, the compounds of formula I can be produced using metal-catalyzed cross-coupling reactions from appropriately functionalized intermediates 7 and 9, where one partner has an organometallic (e.g., zincate, boronate) typically produced from a halide intermediate such as I or Br, and the other partner has a halide such as Br or I (Scheme 7). For example, under Negishi conditions (palladium catalysis), iodide (7;Y 1 =I) The zincate 7 temporarily generated from (hetero)halide aryl 9(Y 2 It can be reacted with Br, I). Iodide 7 can be produced from the associated hydroxy building block 8 by reaction with I2 and PPh3. [ka]

[0209] Alternatively, compounds of formula I having A=(substituted)pyridyl, (substituted)pyrimidinyl, or (substituted)pyridazinyl with a (halo)alkoxy R group were prepared by reacting the compound of formula 10 (Y=F, Cl) with the corresponding alcohol and a suitable base (e.g., NaH or KOtBu) (Scheme 8). Alternatively, when Y=OH, compounds of formula I can be produced from the corresponding alcohol by the Mitsunobu reaction (e.g., using cyanomethyltributylphosphorane). [ka]

[0210] Alternatively, the compound of formula I having A=aliphatic (hetero)ring and C=(hetero)aryl can be produced by coupling the boronic acid derivative 11 (Y=B(OR)2) with iodide 12 under nickel or palladium catalysis. Alternatively, bromide 11 (Y=Br) can be directly bonded with 12 in a photochemical reaction using Ir[dF(CF3)ppy]2(dtbbpy)PF6, NiCl2·DME, dtbbpy and (TMS)3SiH (Scheme 9). [ka]

[0211] Alternatively, a compound of formula I having an aliphatic (hetero) ring A and L1 being oxygen (or containing it) can be converted using a base such as NaH. N In reaction 2, the alcohol of formula 13 (or other simple alcohols or haloalool groups) can be prepared by reacting it with a suitably functionalized building block 14 (wherein Y is a leaving group such as OM or I) (Scheme 10). If necessary, building block 14 can be generated from the corresponding alcohol (Y=OH, 16). [ka]

[0212] Alternatively, a compound of formula I where L1 is (or contains) oxygen and C is a (substituted) aliphatic (hetero) ring or (hetero)aryl (Y is S N The compound (located in a position suitable for Ar substitution) can be prepared by reacting 15 (where Y is a leaving group such as OMs or Cl) with alcohol 16 in the presence of a base such as NaH (Scheme 11). [ka]

[0213] The building blocks of formula 18, where A has an aliphatic (hetero) ring and L1 is oxygen (or contains it), are S using a base such as NaH. N In reaction 2, the alcohol of formula 13 (or other simple alcohol or haloalkyl-hydroxy group) can be prepared by reacting it with a appropriately functionalized building block 17, X 1 is a leaving group such as OM or I, and PG is a protecting group such as Boc. The protecting group can then be removed under standard conditions (e.g., TFA of PG = Boc) (Scheme 12). If necessary, building block 17 is converted to the corresponding alcohol (X 1 It can be generated from (=OH). Alternatively, if the ring C is a phenol-type (hetero)aryl (n=0), building block 18 can be generated from alcohol 17(X) using Mitsunobu conditions (e.g., PS-PPh3, DIAD in THF). 1 It can be generated from (=OH) and then deprotected. [ka]

[0214] Alternatively, the building block of formula 18 (X) is (or contains) oxygen, and C is an aliphatic (hetero) ring, a small (halo)alkyl fragment, or (hetero)aryl. 1 is S N (located in a position suitable for Ar substitution) is 15(X) in the presence of a base such as NaH or KOtBu. 1It can be prepared by reacting a leaving group (such as OMs or Cl) with a properly protected alcohol building block 19, followed by deprotection under standard conditions (for example, if PG=Boc, TFA is used) (Scheme 13). Alternatively, the building block of formula 18, where L1=oxygen and C is (hetero)aryl, can be prepared by reacting alcohol 19 with (hetero)aryl halogen 15(X 1 This can typically be produced by palladium-catalyzed cross-coupling with Br, I), followed by deprotection. [ka]

[0215] The building block of formula 21 having A = (substituted)pyridyl, (substituted)pyrimidinyl, or (substituted)pyridazinyl having a (halo)alkoxy R group is, if necessary, heated at high temperature in a solvent such as DMA, NMP, or DMF, and then converted to formula 20(X 1 A well-protected heteroaryl acid (e.g., as a methyl ester) of =F,Cl can be prepared by reacting it with the corresponding alcohol and a suitable base such as NaH or KOtBu. If a further substitution R2 is required on the heteroaryl, this can typically be done via a commercially available halide (R2=Br,I) followed by a metal-catalyzed cross-coupling reaction (e.g., Suzuki, Negishi, Ir-catalyzed photochemical reaction). The protecting group (if used) can be removed under standard conditions (e.g., alkaline hydrolysis of the methyl ester) (Scheme 14). Alternatively, these building blocks can be produced by synthesizing a suitable bromo or iodo-heterearene using standard techniques, followed by the introduction of an acid (or ester) functional group by a Pd-catalyzed carbonylation reaction. [ka]

[0216] X=CR 8If ring B is a C-bonded (hetero)aryl, amine 3 can be produced by reacting a carbanion (or carbanion equivalent) with a well-protected building block, e.g., tert-butyl 6-oxo-2-azaspiro[3.3]heptane-2-carboxylate, followed by deprotection of the protecting group under standard conditions (e.g., using TFA with PG=Boc). The anion can be produced by direct metallization of heteroaryl 22 (Y=H, e.g., BuLi) or by metal-halogen exchange (using Y=Br, I, e.g., BuLi) (Scheme 15). [ka]

[0217] The building block of formula 24 having A=aliphatic (hetero)ring and C=(hetero)aryl is a well protected boronic acid derivative 11(X 1 =B(OR)2) can be produced by coupling it with iodide 23 under nickel or palladium catalysis. Alternatively, bromide 11(X 1 =Br) can be directly bonded to 23 by photochemical reaction using Ir[dF(CF3)ppy]2(dtbbpy)PF6, NiCl2·DME, dtbbpy and (TMS)3SiH (Scheme 16). [ka]

[0218] The building blocks of equation 27, where C = (hetero)aryl, are Suzuki reactions (e.g., (hetero)aryl halides (X 1The compound can be produced by (Pd(dppf)Cl2,K2CO3, dioxane / H2O) of (Br, I, Cl), followed by hydrogenation (e.g., Pd / C, H2). The required boronate intermediate 25 can be produced by reacting the ketone with 4,4,5,5-tetramethyl-2-[(tetramethyl-1,3,2-dioxaborolan-2-yl)methyl]-1,3,2-dioxaborolan (LiTMP, THF, -78°C) (Scheme 17). Alternatively, the alkene 26 can be produced by a Wittig reaction using the ketone and a suitable triphenylphosphonium bromide (produced from benzyl bromide or heteroaryl equivalent) of ring C. Alternatively, building block 27 can be produced by generating a tosylhydrazone intermediate from an aldehyde on ring A (e.g., by condensation with 4-methylbenzenesulfon hydrazide) prior to deprotection, followed by reaction with the associated (hetero)arylboronic acid (e.g., K2CO3, under Baar-Enga conditions). L1=CR 12 R 13 and R 12 = Carbamoyl, R 13 The building block, which is hydrogen, can be synthesized by a similar strategy using standard techniques, which involves the condensation of (hetero)arylacetonitrile with ketone (52), followed by the hydrogenation of an alkene intermediate produced by hydrolysis of the nitrile and amide formation. [ka]

[0219] The building block of formula 30 having L1 as oxygen and C as phenol or (hetero)arylhydroxy(28) is a nucleophilic (hetero)arylhydroxyanion (produced using a base, e.g., NaH), S N Leaving group X at a position suitable for 2 substitution 1It can be prepared by reacting a well-protected building block 29 having (for example, OM which can be generated from a hydroxy derivative using MsCl, Et3N). Subsequently, it can be deprotected under standard conditions (for example, using TFA in the case of PG=Boc) (Scheme 18). Alternatively, building block 30 can be prepared by reacting phenol with alcohol 29 (X 1 It can be produced by a Mitsunobu reaction with (=OH) (e.g., using DIAD, PPh3, or 2-(tributyl-15-phosphanylidene)acetonitrile), followed by deprotection. [ka]

[0220] Alternatively, the building block of formula 32 having A=aliphatic (hetero)ring and C=(hetero)aryl is a boronic acid derivative 11(X 1 =B(OR)2) can be produced by coupling it with a properly protected halide (Y=I or Br)31 under nickel or palladium catalysis. Alternatively, bromide 11(X 1 Br) can be directly bonded to 31 (Y=I or Br) by photochemical reaction using Ir[dF(CF3)ppy]2(dtbbpy)PF6, NiCl2.DME, dtbbpy, and (TMS)3SiH. Following the coupling, an appropriate deprotection step (e.g., TsOH, PG=Boc) is performed (Scheme 19). [ka]

[0221] Alternatively, the building block of formula 35 having A=aliphatic (hetero)ring, L1=-OCH2- and C=(hetero)aryl may have a leaving group (e.g., X) at the benzyl position (33). 1This can be produced by reacting a (hetero)aryl having =Br) with alcohol 34 in the presence of a base (e.g., NaH). Following the coupling, an appropriate deprotection step (e.g., TsOH or TFA in the case of PG=Boc) is carried out (Scheme 20). This route is also suitable for the case of C=small aliphatic (hetero) ring (e.g., cyclopropyl) or when the ring C is replaced by a small alkyl or haloalkyl fragment. [ka]

[0222] Alternatively, the building block of formula 37 having an L1=CC triple bond can be coupled via Sonogashira coupling (e.g., Pd(PPh3)2Cl2, CuI, TEA) to aryl (hetero)halide 11(X 1 It can be generated from PG=Br or I) and a properly protected alkyne 36, followed by a suitable deprotection step (e.g., TsOH or TFA in the case of PG=Boc) (Scheme 21). [ka]

[0223] B=C linked (hetero)aryl and X=CR 8 The building blocks of formula 38 having the above characteristics can be produced by coupling a well-protected boronic acid derivative 39 (Y=B(OR)2) with an iodide or bromide (Z=I or Br) 40 under nickel or palladium catalysis. Alternatively, bromide 39 (Y=Br) can be directly coupled with 40 (Z=I or Br) in a photochemical reaction using Ir[dF(CF3)ppy]2(dtbbpy)PF6, NiCl2·DME, and dtbbpy(TMS)3SiH (Scheme 22). Alternatively, cross-coupling can be carried out under neutral conditions using zincate transiently produced from 39 (Y=I) and (hetero)aryl halide 40 (Z=I, Br). [ka]

[0224] The building blocks of formula 41 having X=N and B=(hetero)aryl can be prepared by a metal-catalyzed cross-coupling reaction (e.g., Buchwald reaction, Pd catalyst) between a well-protected 42 and an aryl (hetero)halide (Y=Br, I, Cl), followed by deprotection under standard conditions (e.g., using TsOH or TFA in the case of PG=Boc) (Scheme 23). [ka]

[0225] Alternatively, a building block of formula 44 having L1=-SO2NH- can be prepared from sulfonyl chloride 45, appropriately protected (spiro)cyclic amine (46) in the presence of a base such as DIPEA, and then deprotected under standard conditions (for example, using TsOH in the case of PG=Boc) (Scheme 24). This sequence is also suitable when a small alkyl group is present instead of the C ring. [ka]

[0226] Alternatively, the building block (X) of equation 47 where L1=NH and C is (hetero)aryl 1 is S N (Located in a suitable position for Ar substitution) is 48(X 1 is a leaving group such as Cl, Br, etc., and S N A amine building block 49, which is often adjacent to an aromatic nitrogen atom for the Ar reaction, can be prepared by reacting it with a properly protected amine building block 49 in the presence of a base such as DIPEA, followed by deprotection under standard conditions (for example, if PG=Boc, TsOH is used) (Scheme 25). [ka]

[0227] Alternatively, the building block of formula 50 having L1=NH2 or CH2NH can be set by a reductive amination reaction of amine 51 with a well-protected ketone building block 56 in the presence of a reducing agent such as sodium triacetoxyborohydride or sodium cyanoborohydride, followed by deprotection under standard conditions (e.g., using TsOH in the case of PG=Boc) (Scheme 26). [ka]

[0228] Alternatively, the building block of formula 53, in which L1=CH2 and A is N-bonded, can be prepared by the reductive amination reaction of aldehyde 54 with a well-protected heterocycle A(55) in the presence of a reducing agent such as sodium triacetoxyborohydride or sodium cyanoborohydride, followed by deprotection under standard conditions (e.g., using TsOH in the case of PG=Boc) (Scheme 27). The building block of formula 56 can also be produced by performing the same procedure, in which case L1=CH2NH comes from aldehyde 54 and amine 57 (Scheme 28). [ka] [ka]

[0229] Alternatively, the building block of formula 58, in which L1=SO2 and A is N-bonded, can be prepared from sulfonyl chloride 45 and a well-protected heterocycle A(55) in the presence of a base such as DIPEA, followed by deprotection under standard conditions (for example, using TsOH when PG=Boc) (Scheme 29). This sequence is also suitable when A is N-bonded and R1 is C1~C6 alkyl-SO2-. [ka]

[0230] Alternatively, the building block of formula 59, where L1=CH2 and A is bonded to an N bond, is (hetero)arylmethyl halide (X) in a solvent such as ACN in the presence of a base such as K2CO3. 1 It can be prepared by the reductive amination reaction of (=Br,I)60 with a well-protected heterocycle A(55), followed by deprotection under standard conditions (e.g., using TsOH in the case of PG=Boc) (Scheme 30). [ka]

[0231] Alternatively, the building block of formula 59, in which L1=CH2 and A is N-bonded, can be prepared by reductive amination of an acid chloride 61 with a well-protected heterocycle A(55) in the presence of a base (e.g., DIPEA) to form an amide, followed by reduction of the amide (e.g., using a boranetetrahydrofuran complex) and deprotection under standard conditions (e.g., using TsOH in the case of PG=Boc) (Scheme 31). [ka]

[0232] Alternatively, the building block of formula 62 having L1=C(O)NH could be prepared by reacting a well-protected amine 57 with a carboxylic acid 63 to produce an amide 45 using standard amide coupling techniques (e.g., HATU, DIPEA), followed by deprotection under standard conditions (e.g., using TsOH or TFA in the case of PG=Boc) (Scheme 32). [ka]

[0233] Or, L 1A sulfonylurea building block of formula 65 having -NHSO2- or -CH2NHSO2- can be prepared by activating 2-methyl-1-(2-methylimidazole-1-yl)sulfonylimidazole by methylation with methyl trifluoromethanesulfonate, followed by reaction with appropriately protected amine 55, further activation by methylation with methyltrifluoromethanesulfonate and subsequent reaction with amine 51, and finally deprotection under standard conditions (e.g., using TsOH or TFA in the case of PG=Boc) (Scheme 33). Alternatively, the sulfonylurea building block 65 can be generated from sulfuryl chloride, followed by sequential addition of 55 and 51 in the presence of a base such as Et3N or DIPEA, and finally deprotection under standard conditions. [ka]

[0234] L1=bond and C=C bond (hetero)aryl and R 9 A building block having an amine (L2=-NH- or -CH2NH-, where D is an aliphatic heterocycle such as cyclopropyl (66) or C=N bonded heterocycle (67)) is used to obtain an intermediate 70 (X) using the associated amine building block 71 or 72 (typically Pd-catalyzed, Buchwald reaction). 1 The required intermediate 70 can be produced by metal-catalyzed amination of Br (Cl) adjacent to aromatic N. The required intermediate 70 is obtained by transiently generating zincate from a well-protected building block 69 (Y=I) and a suitable dihalogenated (hetero)aryl building block 68 (X 2 X 1 It needs to be more responsive to cross-coupling conditions than X 2 =I or Br, X 1 It can be produced by cross-coupling such as the Negishi reaction between (=Br) and (Scheme 34). Alternatively, intermediate 70 can be produced by a p-tolylsulfonylhydrazono derivative of 69 (Y=N-NH-Ts) and boronic acid 68 (X 2It can be produced by reacting B(OH)2 with a base such as K2CO3. [ka]

[0235] Alternatively, amine 71 or 72 is used in the presence of a base (such as DIEA or K2CO3), S N Ar reaction with (hetero)aryl building block 68(X 1 After reacting with =F) to produce intermediate 73 or 74, a cross-coupling reaction can be carried out with the A ring (typically using Ir[dF(CF3)ppy]2(dtbbpy)PF6,NiCl2.DME, dtbbpy and (TMS)3SiH) using the photochemical reaction between 69 (Y=Br) and halide 73 or 74), followed by deprotection (Scheme 35). Alternatively, R 9 This S that generates amines N The Ar approach is 70 (where X is in the equation). 1 This can be carried out with intermediates such as =F). (Scheme 34) Depending on the case, copper catalyst S N Ar or Ullmann-type reactions were used in reactions 68 and 72 to obtain 74. [ka]

[0236] Building blocks having L1=bonds, C=C bonded (hetero)aryls, and D=N bonded heteroaryls (57) are boronic acid 68(X 1 =B(OH)2,X 2Intermediate 77 can be produced by Chan-Lam coupling (in the presence of Cu(OAc)2) with a heteroaryl compound (=Br), which can then be reacted with a well-protected (spiro)cyclic amine 69 (Y=Br) in a photochemical cross-coupling reaction using Ir[dF(CF3)ppy]2(dtbbpy)PF6,NiCl2.DME,dtbbpy and (TMS)3SiH), followed by deprotection (Scheme 36). Alternatively, in the case of a C-bonded heterocycle, the heterocycle C can be constructed by standard heterocycle synthesis techniques before the photochemical cross-coupling reaction and deprotection. [ka]

[0237] Alternatively, the building block of formula 78, having L1 and L2 bonds and C and D being (hetero)aryl, can be prepared by reacting a well-protected (spiro)cyclic amine (Y=I or Br) in two consecutive cross-coupling reactions followed by deprotection. Most typically, this involves a Ni-catalyzed cross-coupling between 69 (Y=I) and building block 79 having both bromide and boronic acid functional groups, yielding a bromo(hetero)aryl intermediate 80. Intermediate 80 could then be coupled with a boronic acid derivative 81 under Suzuki conditions and subsequently deprotected to obtain 78 (Scheme 37). [ka]

[0238] The building blocks of formula 82, where L1 = bond and L2 = -NHCH2-, can be generated by the reductive amination reaction of a well-protected aldehyde 83 with an amine 84 in the presence of a reducing agent such as sodium triacetoxyborohydride or sodium cyanoborohydride, followed by deprotection under standard conditions (e.g., using TsOH if PG = Boc) (Scheme 38). If necessary, aldehyde 83 can be generated from an acid via a sequence of reduction (e.g., using borane) and oxidation (e.g., using an oxidizing agent such as DMP). [ka]

[0239] The building block of formula 85, where L1=bond and L2=-NHCH2-, can be produced by a Curtius rearrangement of a well-protected acid building block 86 (e.g., using diphenylphosphonic acid azide, benzyl alcohol) and deprotection of the resulting carbamate (e.g., Pd / C,H2) to obtain amine 87, followed by further reductive amination of amine 87 with a suitable aldehyde 88, and then deprotection (Scheme 39). Alternatively, amine 87 can be used in heterocyclic synthesis reactions (e.g., condensation with a suitable 1,3-dione O-(4-nitrobenzoyl)hydroxylamine to produce a pyrazole) to produce an N-bonded heterocyclic D ring. [ka]

[0240] Building block 89 of formula 89, where L1 = bond and L2 = bond and C = heteroaryl, is a building block 90 having a cyano or carboxylic acid group. 1 It can be produced using standard heteroaryl synthesis techniques starting from (=CN,COOH) (Scheme 40). Using a similar sequence, a suitable R on the D ring is used for the building block which is L3=bonded and E=heteroaryl. 14 It is also possible to generate heterocyclic E-algebras from the base. [ka]

[0241] Alternatively, the building block of formula 91 having L1=-NHCH2- can be set up by a reductive amination reaction of amine 92 with a properly protected aldehyde building block 93 in the presence of a reducing agent such as sodium triacetoxyborohydride or sodium cyanoborohydride, followed by deprotection under standard conditions (e.g., using TsOH in the case of PG=Boc) (Scheme 41). [ka]

[0242] Alternatively, the building block of formula 94, having L1 and L2= bonds, with B being a (hetero)aryl and C being an N-linked cyclic amine, can be prepared by reacting a well-protected (spiro)cyclic amine (Y=I or Br) in two consecutive cross-coupling reactions followed by deprotection. Most typically, this involves a Ni-catalyzed cross-coupling of 69 (Y=I) with building block 79 having both bromide and boronic acid functional groups, yielding a bromo(hetero)aryl intermediate 95. Intermediate 95 could then be coupled with amine 96 (e.g., under Buchwald conditions, Pd-catalyzed) and subsequently deprotected to obtain 94 (Scheme 42). [ka]

[0243] L1 and L2 = bond, C = (hetero)aryl, and D = C3~C 10Building blocks of formula 97 having cycloalkyl and 3- to 14-membered heterocyclils can be prepared by reacting a well-protected (spiro)cyclic amine 69 (Y=I or Br) in two consecutive cross-coupling reactions followed by deprotection. Most typically, this involves a negishi cross-coupling of a zincate transiently produced from 69 (Y=I) with building block 98 having two bromide functional groups to obtain a bromo(hetero)aryl intermediate 99. Cross-coupling between intermediate 99 and bromide 100 in a photochemical reaction using Ir[dF(CF3)ppy]2(dtbbpy)PF6, NiCl2.DME, dtbbpy and (TMS)3SiH, followed by deprotection, produces building blocks of general formula 97 (Scheme 43). [ka]

[0244] The building blocks of formula 101, L2=CH2 and D=heteroaryl, can be generated via an Arndt-Eyshtaat homologous sequence of carboxylic acid 90 to produce homologous acid 102, which can then be further derivatized, for example, using standard heterocyclic synthesis techniques, followed by deprotection (Scheme 44). [ka]

[0245] The building block of Equation 1, where L1 = -CH2CH2-, can be generated by a Wittig coupling between the A and C rings to produce an alkene, which can then be reduced.

[0246] The building block of formula 1, in which C is a cyclic amine, D=(hetero)aryl, L1=bond, and L2=-CH2-bonded to the D ring via an N bond, can be produced by reductive amination in the same manner as described above.

[0247] In some cases, the compounds of formula I can also be produced by combining the already described steps with new combinations, for example, by performing the coupling of scheme 1 before completing the individual building blocks using the same sequences as described above.

[0248] In some cases, compounds of formula I can be further functionalized to obtain other compounds of formula I. For example, compounds of formula I having a (hetero)aryl bromide or iodide can be further functionalized with other groups, such as small amines or small alkyls, using metal-catalyzed cross-coupling conditions such as the Buchwald or Suzuki reaction. Building block 1 can also be subjected to further functionalization reactions (e.g., amide formation under standard conditions, alkylation of alcohols (e.g., using NaH and an alkylating agent in DMF), conversion of boron-containing groups to hydroxyls using alkaline peroxide conditions, oxidation of thioethers to sulfones, or placement of small alkyl groups in place of Br or I groups using metal-catalyzed cross-coupling conditions such as the Buchwald or Suzuki reaction) before or after deprotection of the nucleophilic amine to obtain other building blocks of formula 1.

[0249] In some cases, standard functional group interconversion techniques (e.g., conversion of halides to other groups, e.g., small amines, small alkyls using metal-catalyzed cross-coupling conditions (e.g., Buchwald or Suzuki reaction), conversion of boron-containing groups to hydroxyls using alkaline peroxide conditions, cyclization of azidotrimethylsilane with nitriles to produce tetrazoles, Sandmeyer reaction of aniline to bromide, oxidation of thioethers to sulfones, S N Building blocks can be generated from commercially available fragments by two reactions or by alkylation of a hydroxyl or amine group by reductive amination, acylation using an activated carbonyl derivative, or by the placement of an -SO2Me or -SO2CF3 group from an iodo- or bromo-building block using literature techniques. Such techniques may also be used to detail commercially available fragments before, after, or in between the above synthetic sequences.

[0250] Alternatively, especially in the case of C=5-membered ring heteroaryls, the building blocks can be prepared from appropriately functionalized and protected A-ring precursors using standard heterocyclic synthesis techniques (e.g., Heterocyclic Chemistry, Joule JA and Mills K., 5). th (See Edition, Wiley, 2010). For example: In the case of C=1,2,4-oxadiazole, the building block can be produced from ring A having a carboxylic acid derivative via condensation / cyclization with alkylN-hydroxyacetamidine (which can be prepared from alkylnitrile and hydroxylamine hydrochloride). The positional isomer 1,2,4-oxadiazole can also be produced in a similar manner using ring A having a nitrile group and a (halo)alkylcarboxylic acid. In the case of C=1,3,4-oxadiazole, the building block can be prepared from ring A having a carboxylic acid derivative via the formation of a hydrazine carbonyl derivative and condensation / cyclization with a (halo)alkylcarboxylic acid. In the case of C=1,2,3-triazole, the building block can be prepared from ring A having an acetylene derivative and a (halo)alkyl azide, which are transiently produced from an amine via cycloaddition.

[0251] Alternatively, C = heteroaryl, especially A ring = (hetero)aryl, and L 1 In the case of a single bond, the building block can be generated by a metal-catalyzed cross-coupling reaction such as a Buchwald or Ullmann type reaction (in the case of an N-bonded C ring) or a Suzuki reaction.

[0252] In one embodiment, the present invention provides a method for producing a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, as described in any one of schemes 1 to 44.

[0253] In one embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, which is prepared according to any one of the methods described herein.

[0254] MAGL inhibitory activity The compounds of the present invention are MAGL inhibitors. Accordingly, in one embodiment, the present invention provides the use of a compound of formula (I) described herein for inhibiting MAGL in mammals.

[0255] In a further embodiment, the present invention provides compounds of formula (I) described herein for use in methods of inhibiting MAGL in mammals.

[0256] In a further embodiment, the present invention provides the use of a compound of formula (I) described herein for the preparation of a pharmaceutical agent that inhibits MAGL in mammals.

[0257] In a further embodiment, the present invention provides a method for inhibiting MAGL in mammals, the method comprising administering an effective amount of a compound of formula (I) described herein to a mammal.

[0258] The MAGL inhibitory activity of the compound of formula (I) can be profiled by determining the enzyme activity following the hydrolysis of 2-arachidonoylglycerol (2-AG), a natural substrate that produces arachidonic acid, and then mass spectrometry may be performed. This assay will be abbreviated as the "2-AG assay" below.

[0259] The compound of formula (I) may be profiled for MAGL inhibitory activity by determining its enzyme activity following the hydrolysis of 2-arachidonoylglycerol (2-AG), a natural substrate that produces arachidonic acid, and then mass spectrometry may be performed. This assay will be abbreviated as the "2-AG assay" below. The 2-AG assay was performed in a 384-well polypropylene assay plate. Compound dilutions were prepared in a polypropylene plate by a 3-fold dilution step in 100% DMSO to obtain a final concentration range of 12.5 μM to 0.8 pM in the assay. The compound dilutions were added to the MAGL protein in assay buffer (50 mM TRIS, 1 mM EDTA, 0.01% (v / v) Tween-20, 2.5% (v / v) DMSO). After shaking, the plate was incubated at room temperature for 15 minutes. 2-arachidonoylglycerol in the assay buffer was added to initiate the reaction. The final concentrations in the assay were 50 pM for MAGL protein and 8 μM for 2-arachidonoylgrierol. After shaking and incubation at room temperature for 30 minutes, the reaction was stopped by adding two assay volumes of acetonitrile containing 4 μM d8-arachidonic acid. The amount of arachidonic acid formed was tracked by an online SPE system (Agilent Rapidfire) connected to a triple quadrupole mass spectrometer. A C18 SPE cartridge (Agilent G9205A) was used in an acetonitrile / water liquid setup. The mass spectrometer was operated in negative electrospray mode according to mass transitions of 303.1 → 259.1 for arachidonic acid and 311.1 → 267.0 for d8-arachidonic acid. The activity of the compounds was calculated based on the intensity ratio [arachidonic acid / d8-arachidonic acid]. [Table 1] TIFF0007886348000160.tif249169 TIFF0007886348000161.tif248169 TIFF0007886348000162.tif248169 TIFF0007886348000163.tif248169 TIFF0007886348000164.tif248169 TIFF0007886348000165.tif248169 TIFF0007886348000166.tif248169 TIFF0007886348000167.tif249169 TIFF0007886348000168.tif248169 TIFF0007886348000169.tif244169 TIFF0007886348000170.tif244169 TIFF0007886348000171.tif245169 TIFF0007886348000172.tif245169 TIFF0007886348000173.tif245169 TIFF0007886348000174.tif62169

[0260] In one embodiment, the present invention provides compounds of formula (I) as described herein and pharmaceutically acceptable salts or esters thereof, which, when measured by the MAGL assay described herein, exhibit IC50 for MAGL inhibition. 50 The concentration is less than 25 μM, preferably less than 10 μM, and more preferably less than 5 μM.

[0261] In one embodiment, the compounds of formula (I) described herein and their pharmaceutically acceptable salts or esters are measured by the MAGL assay described herein, and have an IC value. 50 The (MAGL inhibition) value is between 0.000001 μM and 25 μM, and certain compounds exhibit IC50. 50 The value is between 0.000005 μM and 10 μM, and furthermore, certain compounds exhibit IC50. 50 The value is between 0.00005 μM and 5 μM.

[0262] Use of the compound of the present invention In one embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, for use as a therapeutically active substance.

[0263] In a further embodiment, the present invention provides the use of compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, for the treatment or prevention of neuroinflammation, neurodegenerative diseases, pain, cancer, and / or mental disorders in mammals.

[0264] In one embodiment, the present invention provides the use of a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, for the treatment or prevention of neuroinflammatory and / or neurodegenerative diseases in mammals.

[0265] In one embodiment, the present invention provides the use of a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, for the treatment or prevention of neurodegenerative diseases in mammals.

[0266] In one embodiment, the present invention provides the use of a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, for the treatment or prevention of cancer in mammals.

[0267] In one embodiment, the present invention provides the use of a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, for the treatment or prevention of inflammatory bowel disease in mammals.

[0268] In one embodiment, the present invention provides the use of a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, for the treatment or prevention of pain in mammals.

[0269] In one embodiment, the present invention provides the use of compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, for the treatment or prevention of multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, anxiety disorders, migraines, depression, hepatocellular carcinoma, colon cancer development, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, and / or pain-associated spasticity in mammals.

[0270] In preferred embodiments, the present invention provides the use of compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, for the treatment or prevention of multiple sclerosis, Alzheimer's disease, and / or Parkinson's disease in mammals.

[0271] In particularly preferred embodiments, the present invention provides the use of a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, for the treatment or prevention of multiple sclerosis in mammals.

[0272] In one embodiment, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, for use in the treatment or prevention of neuroinflammation, neurodegenerative diseases, pain, cancer, and / or mental disorders in mammals.

[0273] In one embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of neuroinflammatory and / or neurodegenerative diseases in mammals.

[0274] In one embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of cancer in mammals.

[0275] In one embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of neurodegenerative diseases in mammals.

[0276] In one embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of inflammatory bowel disease in mammals.

[0277] In one embodiment, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of pain in mammals.

[0278] In one embodiment, the present invention provides compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, for use in the treatment or prevention of multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, anxiety disorders, migraines, depression, hepatocellular carcinoma, colon cancer development, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, and / or pain-associated spasticity in mammals.

[0279] In preferred embodiments, the present invention provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, for use in the treatment or prevention of multiple sclerosis, Alzheimer's disease, and / or Parkinson's disease in mammals.

[0280] In particularly preferred embodiments, the present invention provides compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, for use in the treatment or prevention of multiple sclerosis in mammals.

[0281] In one embodiment, the present invention provides the use of a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment or prevention of neuroinflammation, neurodegenerative diseases, pain, cancer, and / or mental disorders in mammals.

[0282] In one embodiment, the present invention provides the use of a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment or prevention of neuroinflammatory and / or neurodegenerative diseases in mammals.

[0283] In one embodiment, the present invention provides the use of a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a pharmacopoeia for the treatment or prevention of neurodegenerative diseases in mammals.

[0284] In one embodiment, the present invention provides the use of a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a pharmacopoeia for the treatment or prevention of cancer in mammals.

[0285] In one embodiment, the present invention provides the use of a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment or prevention of inflammatory bowel disease in mammals.

[0286] In one embodiment, the present invention provides the use of a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment or prevention of pain in mammals.

[0287] In a further embodiment, the present invention provides the use of compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, for the preparation of pharmaceuticals for the treatment or prevention of multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, anxiety, migraine, depression, hepatocellular carcinoma, colon cancer development, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, and / or pain-associated spasticity in mammals.

[0288] In preferred embodiments, the present invention provides the use of a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a pharmacopoeia for the treatment or prevention of multiple sclerosis, Alzheimer's disease, and / or Parkinson's disease in mammals.

[0289] In particularly preferred embodiments, the present invention provides the use of a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment or prevention of multiple sclerosis in mammals.

[0290] In one embodiment, the present invention provides a method for treating or preventing neuroinflammation, neurodegenerative diseases, pain, cancer, and / or mental disorders in mammals, comprising administering an effective amount of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, to the mammal.

[0291] In one embodiment, the present invention provides a method for treating or preventing neuroinflammatory and / or neurodegenerative diseases in mammals, the method comprising administering to a mammal an effective amount of a compound of formula (I) described herein or a pharmaceutically acceptable salt thereof.

[0292] In one embodiment, the present invention provides a method for treating or preventing neurodegenerative diseases in mammals, the method comprising administering an effective amount of a compound of formula (I) described herein or a pharmaceutically acceptable salt thereof to a mammal.

[0293] In one embodiment, the present invention provides a method for treating or preventing cancer in mammals, the method comprising administering to a mammal an effective amount of a compound of formula (I) described herein or a pharmaceutically acceptable salt thereof.

[0294] In one embodiment, the present invention provides a method for treating or preventing inflammatory bowel disease in mammals, the method comprising administering to a mammal an effective amount of a compound of formula (I) described herein or a pharmaceutically acceptable salt thereof.

[0295] In one embodiment, the present invention provides a method for treating or preventing pain in a mammal, the method comprising administering to a mammal an effective amount of a compound of formula (I) described herein or a pharmaceutically acceptable salt thereof.

[0296] In a further embodiment, the present invention provides a method for treating or preventing multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, anxiety, migraine, depression, hepatocellular carcinoma, colon carcinogenesis, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, pain-related spasticity, abdominal pain, abdominal pain associated with irritable bowel syndrome, and / or visceral pain in mammals, comprising administering an effective amount of a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, to a mammal.

[0297] In preferred embodiments, the present invention provides a method for treating or preventing multiple sclerosis, Alzheimer's disease, and / or Parkinson's disease in mammals, comprising administering an effective amount of a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, to the mammal.

[0298] In a particularly preferred embodiment, the present invention provides a method for treating or preventing multiple sclerosis in mammals, comprising administering an effective amount of a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, to the mammal.

[0299] Pharmaceutical composition and administration In one embodiment, the present invention provides a pharmaceutical composition comprising a compound of formula (I) described herein and a therapeutic inactivating carrier.

[0300] In one embodiment, a pharmaceutical composition according to Example 540 or 541 is provided.

[0301] Compounds of formula (I) and their pharmaceutically acceptable salts and esters may be used as pharmaceuticals (e.g., in the form of pharmaceutical formulations). Pharmaceutical formulations may be administered orally (e.g., in the form of tablets, coated tablets, sugar-coated tablets, hard gelatin capsules and soft gelatin capsules, solutions, emulsions or suspensions), nasally (e.g., in the form of nasal sprays), or rectally (e.g., in the form of suppositories), etc. However, administration may also be parenterally (e.g., intramuscular or intravenous, in the form of injections), etc.

[0302] Compounds of formula (I) and their pharmaceutically acceptable salts and esters can be treated with pharmaceutically inert inorganic or organic adjuvants for the production of tablets, coated tablets, sugar-coated tablets, and hard gelatin capsules. Lactose, corn starch or derivatives thereof, talc, stearic acid or salts thereof, etc., can be used as adjuvants for tablets, sugar-coated tablets, and hard gelatin capsules.

[0303] Suitable adjuvants for soft gelatin capsules include, for example, vegetable oils, waxes, fats, semi-solid substances, and liquid polyols.

[0304] Suitable adjuvants for the production of solutions and syrups include, for example, water, polyols, sucrose, invert sugar, and glucose.

[0305] Suitable adjuvants for injection solutions include, for example, water, alcohol, polyol, glycerol, and vegetable oil.

[0306] Suitable adjuvants for suppositories include, for example, natural or hydrogenated oils, waxes, fats, semi-solid or liquid polyols.

[0307] Furthermore, pharmaceutical preparations may contain preservatives, solubilizers, viscosity enhancers, stabilizers, humectants, emulsifiers, sweeteners, colorants, flavorings, salts to alter osmotic pressure, buffers, masking agents, or antioxidants. They may also contain other substances of therapeutic value.

[0308] Dosages can vary widely and, of course, can be adapted to the individual requirements of each specific case. Generally, for oral administration, a daily dose of about 0.1 mg to 20 mg / kg body weight, preferably about 0.5 mg to 4 mg / kg body weight (e.g., about 300 mg / person), may be appropriate, preferably divided into 1 to 3 individual doses, each of the same amount. However, it is clear that the upper limits given herein can be exceeded where indicated. [Examples]

[0309] The present invention will be better understood by referring to the following embodiments. However, the claims should not be construed as being limited to the scope of these embodiments.

[0310] If the preparation is obtained as a mixture of enantiomers, the pure enantiomers can be separated by the method described herein or by methods known to those skilled in the art, such as chiral chromatography (e.g., chiral SFC) or crystallization.

[0311] Unless otherwise specified, all reaction examples and intermediates were prepared under an argon atmosphere.

[0312] Example 1 (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)azetidine-1-yl)methanone [ka]

[0313] To a solution of (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(1H-1,2,4-triazole-1-yl)methanone (180 mg, 601 μmol) in dry DMF (3 mL), 3-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)azetidine 4-methylbenzenesulfonate (B.1) (261 mg, 631 μmol) and DIPEA (233 mg, 315 μL, 1.8 mmol) were added, and the reaction mixture was stirred at 80°C for 18 hours. The crude reaction mixture was directly subjected to reverse-phase HPLC purification to obtain 232 mg of the desired product. MS(ESI): m / z = 472.3 [M+H] +

[0314] Step a) (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl)(1H-1,2,4-triazole-1-yl)methanone

[0315] To a suspension of 6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptane 2,2,2-trifluoroacetate A.1) (10.0 g, 31.4 mmol) in dry CH2Cl2 (135 mL) cooled to 0°C, DIPEA (12.2 g, 16.5 ml, 94.3 mmol) was added, followed by di(1H-1,2,4-triazole-1-yl)methanone (5.41 g, 33.0 mmol). The reaction mixture was stirred at 0°C for 5 minutes and at room temperature for 30 minutes. The reaction mixture was diluted with dichloromethane, extracted with aqueous Na2CO3 solution (1 M solution), and the organic phase was recovered. It was dried over sodium sulfate and evaporated to dryness to obtain (9.27 g, crude). The batch was used directly without further purification. MS(ESI): m / z = 300.2[M+H] +

[0316] Similar to Example 1, the examples in the table below were generated using building blocks AX and BX. [Table 2] TIFF0007886348000177.tif252169 TIFF0007886348000178.tif245169 TIFF0007886348000179.tif219169 TIFF0007886348000180.tif249169 TIFF0007886348000181.tif253169 TIFF0007886348000182.tif234169 TIFF0007886348000183.tif46169

[0317] Example 3 [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone [ka]

[0318] A mixture of 3-cyclopropyl-1H-1,2,4-triazole (CAS: 1211390-33-8) (21.8 mg, 200 μmol) and [2-[4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)benzoyl]-2-azaspiro[3.3]heptan-6-yl]methanesulfonate (83 mg, 200 μmol) in CH3CN (2.0 mL) was to be mixed with Cs2CO3 (600 μmol) in an 8 mL vial. The mixture was shaken at 100 °C for 16 hours. The mixture was filtered and purified by preparative HPLC to obtain the title compound (23.9 mg, yield 28%). MS(ESI): m / z = 433.3 [M + H] +

[0319] Step a) [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-(6-hydroxy-2-azaspiro[3,3]heptan-2-yl)methanone

[0320] HATU (8.80 g, 23.2 mmol, 8.59 mL) and TEA (6.25 g, 61.7 mmol, 8.59 mL) were added to a solution of 4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)benzoic acid (CAS: 1119452-72-0) (3.8 g, 15.4 mmol) and 2-azaspiro[3.3]heptan-6-ol (2.54 g, 17.0 mmol, HCl salt) in THF (100 mL). The reaction mixture was stirred at 25 °C for 16 hours. The solution was filtered and concentrated under reduced pressure at 40 °C. The residue was purified by flash silica gel chromatography (elution on a 0-40% THF / petroleum ether gradient). The title compound (3.8 g, 10.0 mmol, yield 64.9%) was obtained as a white solid. MS(ESI): m / z = 342.3[M+H] +

[0321] Step b) [2-[4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)benzoyl]-2-azaspiro[3,3]heptan-6-yl]methanesulfonate

[0322] To a solution of [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-(6-hydroxy-2-azaspiro[3.3]heptan-2-yl)methanone (1.00 g, 2.64 mmol) and TEA (534 mg, 5.27 mmol, 734 μL) in DCM (10 mL), MsCl (1.34 g, 11.7 mmol, 905 μL) was added dropwise at 0°C. The resulting mixture was stirred at 0°C for 2 hours. The residue was poured into water (20 mL). The aqueous phase was extracted with DCM (20 mL x 3). The combined organic phase was dried over anhydrous Na2SO4, filtered, and concentrated under vacuum. The title compound (1.5 g, crude) was obtained as a yellow oily substance, which was used directly in the next step without further purification. MS(ESI): m / z = 420.2[M+H] +

[0323] Similar to Example 3, the examples in the table below were produced using their respective heteroarene building blocks in the final step. In some cases, NaOtBu was used instead of Cs2CO3 in the final step. [Table 3] TIFF0007886348000186.tif238169 TIFF0007886348000187.tif224169

[0324] Example 20 1-[2-[4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)benzoyl]-2-azaspiro[3,3]heptan-6-yl]-1,2,4-triazole-3-carbonitriel [ka]

[0325] To a mixture of [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-(6-hydroxy-2-azaspiro[3.3]heptan-2-yl)methanone (Example 3, step a) (68 mg, 200 μmol) and 1H-1,2,4-triazole-3-carbonitrile (CAS: 3641-10-9) (18.8 mg, 200 μmol) in THF (2.0 mL), PS-PPh3 (600 μmol) was added all at once to an 8 mL vial under N2. DIAD (260 μmol) was added to the mixture at 0°C, then the vial was capped and shaken at 30°C for 16 hours. The reaction mixture was filtered, and the solvent was concentrated by Speedvac. The residue was purified by preparative HPLC to obtain the title compound (24.6 mg, 29.4%). MS(ESI): m / z = 418.3[M+H] +

[0326] Similar to Example 20, the examples in the table below were generated using their respective heteroarene building blocks. [Table 4]

[0327] Example 23 [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(6-methyl-3-pyridyl)-2-azaspiro[3,3]heptan-2-yl]methanone [ka]

[0328] A mixture of [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-(6-iodo-2-azaspiro[3.3]heptan-2-yl)methanone (90 mg, 200 μmol), Zn (1 mmol), TMSCl (20 μmol), and 1,2-dibromoethane (20 μmol) in THF (3 mL) was stirred at 65 °C for 1 hour under an N2 atmosphere to obtain a solution. This solution was added dropwise to a mixture of 5-bromo-2-methylpyridine (41 mg, 300 μmol), Pd2(dba)3 (10 μmol), and Q-Phos (10 μmol) in THF (2 mL). After the dropwise addition was complete, the mixture was stirred at 30 °C for 2 hours. The solvent was removed under reduced pressure. The residue was washed with 1.5 mL of water and extracted with SiO (2 mL × 3). The organic layers were combined, dried over anhydrous Na2SO4, and concentrated to obtain a residue. This residue was purified by preparative HPLC to obtain the title compound (11.4 mg, 13.7%). MS(ESI): m / z = 418.3 [M + H] + Step a) [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-(6-iodo-2-azaspiro[3,3]heptan-2-yl)methanone

[0329] To a solution of [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-(6-hydroxy-2-azaspiro[3.3]heptan-2-yl)methanone (Example 3, step a) (0.80 g, 2.1 mmol) and I2 (803 mg, 3.16 mmol, 637 μL) in toluene (30 mL), imidazole (431 mg, 6.33 mmol) and triphenylphosphine (1.11 g, 4.22 mmol) were added. The reaction mixture was stirred at 110 °C for 2 hours. The solution was concentrated under reduced pressure at 50 °C. The residue was purified by flash silica gel chromatography eluting under a 0-100% DCM / petroleum ether gradient to obtain the title compound (0.8 g, 1.60 mmol, yield 75.7%) as a white solid. MS(ESI): m / z = 452.1 [M+H] +

[0330] Example 30 [[6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[5-fluoro-6-[(1-methylcyclopropyl)methoxy]-3-pyridyl]methanone [ka]

[0331] [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-(5,6-difluoro-3-pyridyl)methanone (crude, 0.12 mmol), 1-methylcyclopropanemethanol (103 mg, 1.2 mmol), and TEA (85.7 μL, 0.6 mmol) were dissolved in DMSO (1.0 mL), to which CsF (54.6 mg, 0.36 mmol) was added. The mixture was stirred under microwave at 110 °C for 2 hours. The mixture was filtered and concentrated under reduced pressure to obtain a residue, which was purified by preparative HPLC to obtain the title compound (24.1 mg, 0.052 mmol, yield 43.3%). MS(ESI): m / z = 411.2 [M + H] + .

[0332] Step a) [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-(5,6-difluoro-3-pyridyl)methanone

[0333] To a solution of 6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptane;2,2,2-trifluoroacetate (Example A.2) (24.3 mg, 0.12 mmol) and 5,6-difluoronicotinic acid (CAS: 851386-33-9) (19.1 mg, 0.12 mmol) and TEA (85.7 μL, 0.6 mmol) in ACN (1.0 mL), T3P (78.5 μL, 0.13 mmol) was added. The mixture was stirred at 80°C for 16 hours. The reaction mixture was concentrated under reduced pressure to obtain a residue, which was diluted with NaOH (1.0 M aqueous solution, 0.5 mL) and H2O (3.0 mL) and extracted with RINKAN (3 mL × 3). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure to obtain the title compound, which was used directly without further purification. MS(ESI): m / z = 345.2[M+H] +

[0334] Similar to Example 30, the examples in the table below were generated by using each building block instead of A.2. [Table 5]

[0335] Example 26 [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[5-fluoro-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone [ka]

[0336] To a solution of 6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptane (Example A.1) (24.5 mg, 0.12 mmol), 5-fluoro-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]pyridine-3-carboxylic acid (Example B.4) (0.12 mmol), and TEA (85.7 μL, 0.6 mmol) in ACN (1.0 mL), T3P (78.5 μL, 0.13 mmol) was added. The mixture was stirred at 80°C for 16 hours. The mixture was concentrated under reduced pressure to obtain the residue. The residue was purified by preparative HPLC to obtain the title compound (19.4 mg, 0.042 mmol, yield 35.0%). MS(ESI): m / z = 466.2 [M + H] + .

[0337] Similar to Example 1, the examples in the table below were produced using building blocks AX and BX, respectively. Other typical coupling agents used include HATU, and other typical bases include DIPEA. [Table 6] TIFF0007886348000195.tif246169 TIFF0007886348000196.tif186169

[0338] Example 33 [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[4-(trifluoromethoxy)phenyl]azetidine-1-yl]methanone [ka]

[0339] To a solution of [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-(3-iodoazetidine-1-yl)methanone (92.3 mg, 0.223 mmol) and (4-(trifluoromethoxy)phenyl)boronic acid (69.1 mg) in i-PrOH (3.00 mL), NiI2 (34.8 mg), trans-2-aminocyclohexanol hydrochloride (16.9 mg), and NaHMDS (0.446 mL, 1 M) were added. The mixture was stirred at 80°C for 16 hours. The reaction mixture was concentrated by speedvac. The residue was purified by preparative HPLC (FA as a modifier) ​​to obtain the final compound. MS(ESI): m / z = 448.3 [M + H] + .

[0340] Step a) 3-iodoazetidine

[0341] To a solution of tert-butyl 3-iodoazetidine-1-carboxylate (10 g, 35.3 mmol) in 2,2,2-trifluoroethanol (30 mL), ethoxyethane trifluoroborane; hydrogen fluoride (14.9 g, 45.9 mmol, 12.60 mL, purity 50-55%, 1.3 equivalents) was added. The mixture was stirred at 25°C for 16 hours. The solvent was removed under reduced pressure, and 50 mL of DCM was added. The mixture was stirred at 25°C for 30 minutes. The mixture was then filtered to obtain a white solid. The crude product 3-iodoazetidine (7.78 g, crude, HBF4 salt), as a pale yellow solid, was used in the next step without further purification. MS(ESI): m / z = 184.1 [M + H] + .

[0342] Step b) [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-(3-iodoazetidine-1-yl)methanone

[0343] To a solution of 3-iodoazetidine (2.69 g, 9.95 mmol, HBF₄ salt) in DCM (80 mL), DIEA (5.14 g, 39.8 mmol, 6.93 mL) and triphosgene (974 mg, 3.28 mmol) were added at 0°C. The mixture was stirred at 0°C for 30 minutes, and then 6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptane (A.1) (3.78 g, 9.95 mmol, 1 equivalent, 2HBF₄ salt) and DIEA (2.57 g, 19.9 mmol, 3.47 mL) were added. The mixture was then stirred at 25°C for 2 hours. The mixture was washed with 40 mL of H₂O and extracted with DCM (60 mL × 2). The organic layers were combined, dried over anhydrous Na₂SO₄, and concentrated to obtain the crude product. The residue was purified by flash silica gel chromatography under a 0-70% THF / petroleum ether gradient to obtain the title compound (1.54 g, 2.86 mmol, yield 28.7%) as a white solid. MS(ESI): m / z = 414.0[M+H] + .

[0344] Similar to Example 33, the examples shown in the table below were produced using commercially available boronic acid building blocks. [Table 7]

[0345] Example 35 6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[4-(1,1-difluoroethyl)phenyl]azetidine-1-yl]methanone [ka]

[0346] To a solution of (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-iodoazetidine-1-yl)methanone (Example 33, step b) (92.3 mg, 0.223 mmol) and (4-(1,1-difluoroethyl)phenyl)boronic acid (62.3 mg, 0.335 mmol) in DMF (3.0 mL), aqueous Cs2CO3 (2.0 M, 335 μl, 0.669 mmol), CyJohn Phos (3.86 mg, 0.011 mmol), and Pd2(dba)3 (10.2 mg, 0.011 mmol) were added. The mixture was stirred at 80°C for 16 hours. The reaction mixture was concentrated using Speedvac. The residue was purified by preparative HPLC, and then further purified by preparative TLC to obtain the title compound (13.4 mg). MS(ESI): m / z = 428.2 [M + H] + .

[0347] Example 84 [3-[2-chloro-4-(trifluoromethoxy)phenyl]azetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone [ka]

[0348] In a solution of 1-bromo-2-chloro-4-(trifluoromethoxy)benzene (CAS:892845-59-9) (55.1 mg, 200 μmol) in DME (1.0 mL), (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-iodoazetidine-1-yl)methanone (actual) was added in a glove box. Example 33, step b): (41.3 mg, 100 μmol), Na2CO3 (42.4 mg, 400 μmol), Ir[dF(CF3)ppy]2(dtbbpy)PF6 (1.1 mg, 1 μmol), NiCl2.DME (1.1 mg, 0.05 equivalent), dtbbpy (1.3 mg, 5 μmol, 0.05 equivalent), and (TMS)3SiH (37.2 mg, 150 μmol) were added. The mixture was stirred at 25°C for 16 hours under a 72 W blue LED strip. The mixture was filtered and washed with 1 mL of water. The mixture was then extracted with HCl (2 mL × 2). The organic layer was dried over anhydrous Na2SO4 and concentrated to obtain the crude product. The crude product was purified by preparative HPLC to obtain the title compound (16.4 mg). MS(ESI): m / z = 482.2 [M + H] + .

[0349] Similar to Example 84, the examples shown in the table below were produced using commercially available bromide building blocks. [Table 8]

[0350] Example 40 [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-methoxy-4-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone [ka]

[0351] To a solution of 6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptane 4-methylbenzenesulfonate (A.1; salt) (40 mg, 106 μmol, equivalent: 1) in acetonitrile (100 μL), triethylamine (75.3 mg, 104 μL, 744 μmol) was added, followed by di(1H-1,2,4-triazole-1-yl)methanone (17.4 mg, 106 μmol). The mixture was stirred at room temperature for 3 hours. 6-(2-methoxy-4-(trifluoromethyl)benzyl)-2-azaspiro[3.3]heptane 2,2,2-trifluoroacetate (B.8) (42.4 mg, 106 μmol) was added, and the mixture was stirred at 70°C for 16 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic layers were dried over MgSO4, filtered, and concentrated under vacuum to obtain a crude residue. This residue was then subjected to rpHPLC for purification to obtain the title compound (11 mg, 20%) as a colorless amorphous solid. MS(ESI): m / z = 515.3 [M + H] + .

[0352] Similar to Example 40, the examples in the table below were produced using building blocks AX and BX, respectively. In some cases, other salts of A.1 (e.g., trifluoroacetate) or alternative bases such as DIPEA were used. [Table 9] TIFF0007886348000204.tif238169 TIFF0007886348000205.tif214169 TIFF0007886348000206.tif123169

[0353] Example 42 6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[2-fluoro-4-(trifluoromethoxy)phenoxy]-2-azaspiro[3.3]heptan-2-yl]methanone [ka]

[0354] To a solution of 2-fluoro-4-(trifluoromethoxy)phenol (39.1 mg, 199 μmol) in dry DMF (1 mL), NaH (7.97 mg, 199 μmol) was added. The reaction mixture was stirred at room temperature for 10 minutes, followed by the addition of 2-(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl)-2-azaspiro[3.3]heptan-6-ylmethanesulfonate (70 mg, 166 μmol). The reaction mixture was stirred at 90°C for 18 hours. The crude reaction solution was directly subjected to reverse-phase HPLC purification to obtain the title compound (74.3 mg, 84.1%). MS(ESI): m / z = 522.3 [M + H] + .

[0355] Step a) (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-hydroxy-2-azaspiro[3.3]heptan-2-yl)methanone

[0356] To a solution of (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(1H-1,2,4-triazole-1-yl)methanone (Example 1, step a) (350 mg, 1.17 mmol) in dry DMF (7 mL) under an inert atmosphere, 2-azaspiro[3.3]heptan-6-ol (159 mg, 1.4 mmol) and DIPEA (378 mg, 511 μL, 2.92 mmol) were added. The reaction mixture was then stirred at 80°C for 20 hours. Further additions of 2-azaspiro[3.3]heptan-6-ol (79.4 mg, 702 μmol) and DIPEA (151 mg, 204 μL, 1.17 mmol) were added, and the reaction mixture was stirred again at 80°C for 6 hours. Volatile substances were removed under vacuum, and the crude residue was purified by flash chromatography using an eluate mixture of dichloromethane and methanol (2%-15%) to obtain the impure title compound (393 mg). This was then purified again by flash chromatography (eluate mixture of heptane and Â:EtOH 3:1 solution (60%-100%)) to obtain the title compound (301 mg, 73.5%). MS(ESI): m / z = 344.3 [M+H] + .

[0357] Step b) 2-(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl)-2-azaspiro[3.3]heptan-6-ylmethanesulfonate

[0358] (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-hydroxy-2-azaspiro[3.3]heptan-2-yl)methanone (300 mg, 874 μmol) was dissolved in dry CH2Cl2 (8 mL) to which triethylamine (177 mg, 244 μL, 1.75 mmol) and methanesulfonyl chloride (120 mg, 81.4 μL, 1.05 mmol) were added. The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with dichloromethane, extracted with water, and the organic phase was recovered. The aqueous phase was back-extracted with dichloromethane. The combined organic phase was dried over sodium sulfate and evaporated to dryness to obtain the crude title compound (360 mg), which was used without further purification. MS(ESI): m / z = 422.4 [M + H] + .

[0359] Similar to Example 42, the examples shown in the table below were produced using commercially available phenol / alcohol building blocks. [Table 10] TIFF0007886348000209.tif102169

[0360] Example 55 [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[6-[2-(trifluoromethyl)pyrimidine-4-yl]oxy-2-azaspiro[3,3]heptan-2-yl]methanone [ka]

[0361] To a solution of (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-hydroxy-2-azaspiro[3.3]heptan-2-yl)methanone (Example 42, step a)) (60 mg, 175 μmol) in 1 mL of dry DMF, NaH (7.34 mg, 183 μmol) was added under an inert atmosphere. The reaction mixture was stirred at room temperature for 10 minutes, followed by the addition of 4-chloro-2-(trifluoromethyl)pyrimidine (38.3 mg, 210 μmol). The reaction mixture was then stirred at 90°C for 18 hours. The crude reaction product was directly subjected to reverse-phase HPLC purification to obtain the title compound (36.4 mg). MS(ESI): m / z = 490.3 [M + H] + .

[0362] Similar to Example 55, the examples shown in the table below were produced using commercially available chloro-heteroaryl building blocks. [Table 11] TIFF0007886348000212.tif156169

[0363] Example 67 [6-(5-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-yl]methanone [ka]

[0364] To a solution of 4-nitrophenyl 6-(5-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate (25 mg, 67.7 μmol) in acetonitrile (1 mL), TEA (34.2 mg, 47.2 μL, 338 μmol) was added, followed by the addition of 3-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)azetidine 4-methylbenzenesulfonate (B.1) (42 mg, 102 μmol). The mixture was heated at 70°C for 15 hours. Volatile substances were removed under reduced pressure. The crude substance was purified by column chromatography using DCM:methanol (0-10% methanol) as the solvent. The title compound (12 mg, 24.2 μmol, yield 35.7%) was obtained as a grayish-white solid. MS(ESI): m / z = 472.4 [M+H] + .

[0365] Step a) 4-Nitrophenyl 6-(5-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carboxylate

[0366] To a solution of tert-butyl 6-(5-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carboxylate (positional isomer by-product produced in step b of Example A.1)) (457 mg, 1.5 mmol) in DCM (12.2 mL), 2,2,2-trifluoroacetic acid (1.71 g, 1.15 mL, 15 mmol) was added. The mixture was stirred at room temperature for 5 hours. The solvent was removed, and the TFA was co-evaporated with toluene. The crude substance was redissolved in dry DCM (12.2 mL). The mixture was cooled to 0°C. TEA (760 mg, 1.05 mL, 7.51 mmol) was added, followed by 4-nitrophenylcarbonochloride (303 mg, 1.5 mmol). The mixture was warmed to room temperature and stirred for a further 12 hours. The solvent was removed under reduced pressure. The crude substance was purified by column chromatography using heptane / ethyl acetate (1:1) as the solvent. The title compound (195 mg, 528 μmol, yield 35.2%) was obtained as a pale yellow solid. MS(ESI): m / z = 370.1[M+H]+ .

[0367] Example 88 [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[4-[5-(2,2-dimethylpropyl)-1,2,4-oxadiazole-3-yl]phenyl]methanone [ka]

[0368] To a suspension of 4-(5-neopentyl-1,2,4-oxadiazole-3-yl)benzoic acid (B.32) (44.6 mg, 171 μmol) in dry DMF (1 mL), DIPEA (90.6 mg, 122 μL, 701 μmol) and HATU (65.2 mg, 171 μmol) were added. The reaction mixture was stirred at room temperature for 15 minutes, followed by the addition of 6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptanbis(4-methylbenzenesulfonate) (A.1; tosylate) (90 mg, 156 μmol). The reaction mixture was stirred at room temperature for 60 minutes, cooled, and directly subjected to reverse-phase HPLC purification to obtain the title compound (41.6 mg). MS(ESI): m / z = 447.4 [M + H] + .

[0369] Example 90 [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(3-cyclobutyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone [ka]

[0370] To tert-butyl 6-(3-cyclobutyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate (165 mg, 518 μmol) in DCM (4.21 mL), TFA (591 mg, 399 μL, 5.18 mmol) was added. The mixture was stirred at room temperature for 3 hours. The solvent was removed under reduced pressure, and the TFA was co-evaporated with toluene. The TFA salt was redissolved in DMF (4.21 mL), and DIPEA (402 mg, 543 μL, 3.11 mmol) was added, followed by 4-(5-(tert-butyl)-1,2,4-oxadiazole-3-yl)benzoic acid (128 mg, 518 μmol) and 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosfinan 2,4,6-trioxide (1.32 g, 942 μL, 2.07 mmol). The mixture was stirred at room temperature for 14 hours. The mixture was diluted with ethyl acetate and washed with water. The aqueous phase was extracted twice with ethyl acetate. The organic phase was washed with water and brine and dried over MgSO4. The crude substance was purified by column chromatography using DCM / methanol (0-10% methanol) as the solvent, followed by further purification by column chromatography eluting with DCM / methanol (5% methanol). The title compound (79 mg, 163 μmol, 31.4% yield) was obtained as a white solid. MS(ESI): m / z = 447.4 [M + H] + .

[0371] Step a) tert-butyl6-(3-cyclobutyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carboxylate

[0372] To a solution of tert-butyl 6-((methylsulfonyl)oxy)-2-azaspiro[3.3]heptane-2-carboxylate (CAS: 1239320-11-6) (513 mg, 1.76 mmol) in DMF (13.5 mL), cesium carbonate (2.65 g, 8.12 mmol) was added, followed by the addition of 3-cyclobutyl-1H-1,2,4-triazole (250 mg, 2.03 mmol). The mixture was stirred at 100°C for 24 hours. The mixture was diluted with ethyl acetate and washed with water. The aqueous phase was extracted twice with ethyl acetate. The organic phase was washed with water and brine and dried over MgSO4. The crude substance was purified by HPLC to obtain the title compound as a white solid (170 mg, yield 26.3%). MS(ESI): m / z = 319.3 [M + H] + .

[0373] Example 112 [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-[4-(difluoromethoxy)-2-fluorophenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone [ka]

[0374] To a solution of (3aR,5s,6aS)-5-(4-(difluoromethoxy)-2-fluorophenoxy)octahydrocyclopenta[c]pyrrole (approximately 0.44 mmol, crude) in DCM (5 mL), TEA (2.64 mmol, 6.0 equivalents) was added. The mixture was cooled to 0°C. Triphosgene (0.145 mmol, 0.33 equivalents) in DCM (1 mL) was added to the mixture. The mixture was then stirred at 25°C for 0.5 hours. 6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptane (A.1) (0.44 mmol) was added. The mixture was stirred at 25°C for 2 hours. The mixture was quenched with H2O (2 mL), extracted with DCM (3 mL x 2), dried over anhydrous Na2SO4, and concentrated to obtain the crude product. The crude substance was purified by preparative HPLC to obtain (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)((3aR,5s,6aS)-5-(4-(difluoromethoxy)-2-fluorophenoxy)hexahydrocyclopenta[c]pyrrole-2(1H)-yl)methanone (24.4 mg, 0.047 mmol, 10.7%). MS(ESI): m / z = 518.2[M+H] + .

[0375] Step a) (3aR,5s,6aS)-tert-butyl 5-(4-(difluoromethoxy)-2-fluorophenoxy)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate

[0376] To a solution of 4-(difluoromethoxy)-2-fluorophenol (0.55 mmol, 1.25 equivalents) in DCM (5 mL), (3aR,5r,6aS)-tert-butyl 5-hydroxyhexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (100 mg, 0.44 mmol, 1.0 equivalent), PS-TPP (2.2 mmol, 5.0 equivalents, 3 mmol / g), and DIAD (0.88 mmol, 2.0 equivalents, 1.9 M in toluene) were added in a glove box filled with N2. The mixture was shaken at 30°C for 16 hours and monitored by LCMS. The mixture was filtered, quenched with saturated NaHCO3 aqueous solution (2.0 mL), extracted with DCM (3.0 mL × 2), and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure to obtain the title compound, which was used in the next step without further purification. MS(ESI): m / z = 332.2[M+H-56] + .

[0377] Step b) (3aR,5s,6aS)-5-(4-(difluoromethoxy)-2-fluorophenoxy)octahydrocyclopenta[c]pyrrole

[0378] To a solution of (3aR,5s,6aS)-tert-butyl 5-(4-(difluoromethoxy)-2-fluorophenoxy)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (approximately 0.44 mmol, crude, 1.0 equivalent) in DCM (2 mL), 2 mL of HCl solution (8.0 mmol, 4.0 M in dioxane) was added. The mixture was shaken at 30°C for 2 hours. The solvent was removed by Speedvac to obtain the crude title compound, which was used in the next step without purification. MS(ESI): m / z = 288.1 [M + H] + .

[0379] Similar to Example 112, the examples in the table below were produced using the following commercially available phenol building blocks in step a). [Table 12] TIFF0007886348000218.tif216169 TIFF0007886348000219.tif206169 TIFF0007886348000220.tif215169 TIFF0007886348000221.tif204169 TIFF0007886348000222.tif215169 TIFF0007886348000223.tif220169 TIFF0007886348000224.tif145169

[0380] Example 139 [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[2-[2-(difluoromethyl)phenyl]ethynyl]azetidine-1-yl]methanone [ka]

[0381] To a solution of 6-(4-cyclopropyl-1H-imidazole-1-yl)-2-azaspiro[3.3]heptane (A.2, free base) (35 mg, 172 μmol) in acetonitrile (1.98 mL), Hünig base (63 mg, 85.1 μL, 487 μmol), followed by di(1H-1,2,4-triazole-1-yl)methanone (28.2 mg, 172 μmol), was added at 0°C, and the reaction mixture was stirred at room temperature for 1 hour. Then, Hünig base (63 mg, 85.1 μL, 487 μmol, equivalent: 4) was added, followed by 3-((2-(difluoromethyl)phenyl)ethynyl)azetidine (B.46) (25.3 mg, 122 μmol) as a colorless wax. MS(ESI): m / z = 437.2 [M + H] + .

[0382] Similar to Example 139, the examples in the following table were generated using building blocks AX and BX. [Table 13]

[0383] Example 142 [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[5-methyl-6-[(1-methylcyclopropyl)methoxy]-3-pyridyl]methanone [ka]

[0384] To a stirred suspension of NaH (6.25 mg, 156 μmol) in DMF (574 μL), (1-methylcyclopropyl)methanol (13.5 mg, 156 μmol) was added under inert conditions and at room temperature, and the mixture was stirred for 15 minutes. Then, a solution of (6-(4-cyclopropyl-1H-imidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-fluoro-5-methylpyridine-3-yl)methanone (26.6 mg, 78.1 μmol) in DMF (574 μL) was added, and the reaction mixture was stirred at room temperature for 5.5 hours. The mixture was diluted with ethyl acetate, washed with water, and the aqueous phase was extracted with ethyl acetate. The combined organic matter was washed with brine, dried over sodium sulfate, filtered, and concentrated under vacuum. The residue was purified by flash chromatography eluting with DCM:MeOH 100:0~95:10. The title compound (8.8 mg, 20.6 μmol, 26.3% yield) was obtained as a viscous, colorless oil. MS(ESI): m / z = 407.4 [M + H] +

[0385] Step a) (6-(4-cyclopropyl-1H-imidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-fluoro-5-methylpyridine-3-yl)methanone

[0386] To a stirred solution of 6-(4-cyclopropyl-1H-imidazole-1-yl)-2-azaspiro[3.3]heptane(A.2)bis(4-methylbenzenesulfonate) (150 mg, 274 μmol), 6-fluoro-5-methylnicotinic acid (40.4 mg, 260 μmol), Huenig base (142 mg, 191 μL, 1.1 mmol), and finally HATU (115 mg, 301 μmol) were added in DMF (1.4 mL) under an inert argon atmosphere, and the solution was stirred overnight at room temperature. The mixture was diluted with HCl (5 mL), washed with water, and extracted with HCl. The organic layers were combined, washed with sodium bicarbonate and brine, dried over sodium sulfate, filtered, and concentrated under vacuum to obtain the crude substance as a yellow oil. Purification by reverse-phase HPLC yielded the title compound (26.6 mg, 78.1 μmol, yield 28.5%) as a colorless liquid. MS(ESI): m / z = 341.2[M+H] +

[0387] Similar to Example 142, the examples in the following table were generated using the respective building block AX. [Table 14]

[0388] Example 146 [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(4-methylpyrazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone [ka]

[0389] A mixture of T3P (1.3 mL, 1.34 mmol), DIEA (288 mg, 2.23 mmol), 4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)benzoic acid (CAS: 1119452-72-0) (110 mg, 0.450 mmol), and 6-(4-methylpyrazole-1-yl)-2-azaspiro[3.3]heptane; 2,2,2-trifluoroacetic acid (A.4) (130 mg, 0.450 mmol) in DMF (6.5 mL) was stirred at 20°C for 12 hours. The mixture was purified by preparative HPLC (FA) and lyophilized to obtain the title compound (18.9 mg, 0.050 mmol, yield 10.2%) as a white solid. MS (ESI): m / z = 406.4 [M + H] +

[0390] Similar to Example 146, the examples in the following table were generated using building blocks AX and BX. [Table 15]

[0391] Example 149 [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[8-[[1-(trifluoromethyl)cyclopropyl]methoxy]-5-azaspiro[2.5]octane-5-yl]methanone [ka]

[0392] To a solution of 6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptane; 2,2,2-trifluoroacetic acid (A.1) (55.0 mg, 0.170 mmol) and DIPEA (67.0 mg, 0.520 mmol) in ACN (2 mL), (4-nitrophenyl)3-ethyl-3-methyl-4-[[1-(trifluoromethyl)cyclopropyl]methoxy]piperidine-1-carboxylate (55.8 mg, 0.130 mmol) was added, and the mixture was stirred at 90°C for 12 hours. The mixture was concentrated, and the residue was purified by preparative HPLC (0.225% v / v FA), lyophilized, and the title compound (10.6 mg, 0.020 mmol, yield 12.1%) was obtained as a yellow foam. MS(ESI): m / z = 480.2 [M + H] +

[0393] Step a) tert-butyl 8-[[1-(trifluoromethyl)cyclopropyl]methoxy]-5-azaspiro[2.5]octane-5-carboxylate

[0394] To a solution of tert-butyl 8-hydroxy-5-azaspiro[2.5]octane-5-carboxylate (CAS: 955028-95-2) (100 mg, 0.440 mmol) in DMF (2 mL), NaH (35.2 mg, 0.880 mmol) was added at 0°C. The reaction mixture was stirred for 30 minutes, and then [1-(trifluoromethyl)cyclopropyl]methylmethanesulfonate (CAS: 1262400-04-3) (144 mg, 0.660 mmol) was added, and the mixture was stirred at 50°C for 12 hours. The mixture was poured into a saturated aqueous solution of NH4Cl (10 mL), extracted with siRNA (3 mL, 3 times), washed with brine, dried over Na2SO4, concentrated, and the residue purified by silica gel column (PE:siRNA = 30:1-20:1) to obtain the title compound (54 mg, 0.150 mmol, yield 35.1%) as a pale yellow oil. MS(ESI): m / z = 250.4 [M-C4H8+H] +

[0395] Step b) 8-[[1-(trifluoromethyl)cyclopropyl]methoxy]-5-azaspiro[2.5]octantrifluoroacetate

[0396] To a solution of tert-butyl 8-[[1-(trifluoromethyl)cyclopropyl]methoxy]-5-azaspiro[2.5]octane-5-carboxylate (50.0 mg, 0.140 mmol) in DCM (1 mL), TFA (0.1 mL, 0.140 mmol) in DCM (1 mL) was added at 0°C, and the mixture was then stirred at 25°C for 1 hour. The reaction mixture was concentrated under reduced pressure to obtain the title compound (50 mg, 0.140 mmol, yield 96.2%) as a crude yellow oil, which was used in the next step without further purification. MS(ESI): m / z = 250.1[M+H] +

[0397] Step c) (4-nitrophenyl)3-ethyl-3-methyl-4-[[1-(trifluoromethyl)cyclopropyl]methoxy]piperidine-1-carboxylate

[0398] To a solution of 4-nitrophenyl chloroformate (30.5 mg, 0.150 mmol) in ACN (1.25 mL), DIPEA (44.4 mg, 0.340 mmol) was added while maintaining the temperature at 0°C, followed by the addition of 8-[[1-(trifluoromethyl)cyclopropyl]methoxy]-5-azaspiro[2.5]octanetrifluoroacetate (50.0 mg, 0.140 mmol). The reaction mixture was stirred at 90°C for 12 hours. The reaction mixture was concentrated under reduced pressure and purified by preparative TLC (PE:Â=2:1) ​​to obtain the title compound (52.0 mg, 0.130 mmol, yield 91.2%) as a yellow oil. MS(ESI): m / z=415.4[M+H] +

[0399] Similar to Example 150, the examples in the following table were generated using building blocks AX and BX. [Table 16]

[0400] Example 153 [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[5-(trifluoromethyl)-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone [ka]

[0401] To a solution of 5-(trifluoromethyl)-6-((1-(trifluoromethyl)cyclopropyl)methoxy)nicotinic acid (100 mg, 304 μmol) in dry DMF (2 mL), DIPEA (157 mg, 212 μl, 1.22 mmol) and HATU (121 mg, 319 μmol) were added. The reaction mixture was stirred at room temperature for 10 minutes, followed by the addition of 6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptanbis(4-methylbenzenesulfonate) (A.1, tosylate) (183 mg, 334 μmol). The reaction mixture was stirred at room temperature for 3 hours. The crude reaction mixture was directly subjected to reverse-phase HPLC purification to obtain the title compound (78.9 mg, yield 49.4%). MS(ESI): m / z = 516.3 [M+H] +

[0402] Step a) 5-(trifluoromethyl)-6-((1-(trifluoromethyl)cyclopropyl)methoxy)nicotinic acid

[0403] To a solution of (1-(trifluoromethyl)cyclopropyl)methanol (342 mg, 2.44 mmol) in dry DMSO (5 ml), potassium tert-butoxide (547 mg, 4.88 mmol) was added under an inert atmosphere. The reaction mixture was then stirred at room temperature for 5 minutes, followed by the addition of 6-chloro-5-(trifluoromethyl)nicotinic acid (CAS: 1110782-41-6) (500 mg, 2.22 mmol). The reaction mixture was then stirred at room temperature for 10 minutes. The reaction mixture was then stirred at room temperature for 1 hour. Potassium tert-butoxide (124 mg, 1.11 mmol) was added, and the reaction mixture was stirred again at room temperature for 1 hour. The reaction mixture was then partitioned between ethyl acetate and 1N aqueous HCl. The organic phase was recovered, and the aqueous phase was back-extracted with ethyl acetate. The combined organic phase was dried over sodium sulfate and concentrated under vacuum. Next, the crude solution (residual DMSO) was poured into a small amount of 1M HCl aqueous solution to induce precipitation and obtain a rubbery solid. Then, the entire fraction was evaporated to dryness using a centrifugal evaporator to obtain the crude title compound, which was used in the next step without further purification (687 mg, yield 84.7%). MS(ESI): m / z = 330.1[M+H] +

[0404] Example 154 [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[5-(oxetan-3-yl)-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone [ka]

[0405] To a solution of 5-(oxetan-3-yl)-6-((1-(trifluoromethyl)cyclopropyl)methoxy)nicotinic acid (60 mg, 189 μmol) in dry DMF (1 mL), DIPEA (85.5 mg, 116 μL, 662 μmol) and HATU (75.5 mg, 199 μmol) were added. The reaction mixture was then stirred at room temperature for 10 minutes, followed by the addition of 6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptane 2,2,2-trifluoroacetate (A.1) (66.2 mg, 208 μmol). The reaction mixture was then stirred at room temperature for 18 hours. The crude reaction solution was directly purified by reverse-phase HPLC to obtain 77.2 mg of the desired product (85% purity). The previous fraction was purified again by SFC to obtain 52.4 mg of the title compound. MS(ESI): m / z = 504.3[M+H] +

[0406] Step a) Methyl 5-bromo-6-((1-(trifluoromethyl)cyclopropyl)methoxy)nicotinate

[0407] To a solution of (1-(trifluoromethyl)cyclopropyl)methanol (294 mg, 2.1 mmol) in dry DMF (11 mL), NaH (83.8 mg, 2.1 mmol) was added under an inert atmosphere. The reaction mixture was then stirred at room temperature for 5 minutes, followed by the addition of methyl 5-bromo-6-chloronicotinate (500 mg, 2 mmol), and the reaction mixture was stirred at room temperature for 10 minutes. The reaction mixture was then stirred at room temperature for 18 hours. The reaction mixture was quenched by adding a few drops of saturated NH4Cl aqueous solution, diluted with ethyl acetate, and then washed with NaHCO3 1M solution. The organic phase was collected, and the aqueous phase was back-extracted with ethyl acetate. The combined organic phase was dried over sodium sulfate and evaporated to dryness. The crude residue was purified by flash chromatography eluting with a mixture of heptane and ethyl acetate (5%-50%) to obtain the title compound (577 mg, yield 80%). MS(ESI): m / z = 354.1 [M + H] +

[0408] Step b) Methyl 5-(oxetan-3-yl)-6-((1-(trifluoromethyl)cyclopropyl)methoxy)nicotinate

[0409] Under an inert atmosphere, 3-bromooxetane (313 mg, 2.29 mmol), tris(trimethylsilyl)silane (379 mg, 470 μL, 1.52 mmol), (Ir[dF(CF3)ppy]2(dtbpy))PF6 (17.1 mg, 15.2 μmol), and sodium carbonate (323 mg, 3.05 mmol) were added to a solution of methyl 5-bromo-6-((1-(trifluoromethyl)cyclopropyl)methoxy)nicotinate (540 mg, 1.52 mmol) in dry DME (12 mL). A suspension of 16.8 mg of nickel(II) chloride ethylene glycol dimethyl ether complex and 20.5 mg of 4,4-di-tert-butyl-2,2'-dipyridyl in 1 mL of dry DME was stirred at room temperature under an inert atmosphere for 10 minutes. 0.1 mL of this stirred suspension was added to the previous reaction mixture, and the reaction was stirred at room temperature under blue LED irradiation for 18 hours. The reaction mixture was diluted with ethyl acetate, extracted with 1 M aqueous Na2CO3 solution, and the organic phase was recovered. The aqueous phase was back-extracted with ethyl acetate. The combined organic phase was dried over sodium sulfate and evaporated to dryness. The crude material was purified by flash chromatography using a mixture of heptane and ethyl acetate (5%-60%) to obtain the title compound (268 mg, 50% yield). MS(ESI): m / z = 332.1 [M+H] +

[0410] Step c) 5-(oxetan-3-yl)-6-((1-(trifluoromethyl)cyclopropyl)methoxy)nicotinic acid

[0411] To a solution of methyl 5-(oxetan-3-yl)-6-((1-(trifluoromethyl)cyclopropyl)methoxy)nicotinate (268 mg, 809 μmol) in methanol (5 mL), 324 μL, 1.62 mmol, of 5.0 M aqueous NaOH was added, and the reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was then partitioned between ethyl acetate and 0.1 M aqueous HCl, the organic phase was recovered, and the aqueous phase was back-extracted with ethyl acetate. The combined organic phase was dried over sodium sulfate and evaporated to dryness to obtain the title compound (244 mg), which was used without further purification. MS(ESI): m / z = 318.1 [M + H] +

[0412] Example 155 [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[4-[[1-(trifluoromethyl)cyclopropyl]methoxymethyl]-1-bicyclo[2.2.2]octanyl]methanone [ka]

[0413] To a solution of 6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[1-(hydroxymethyl)-4-bicyclo[2.2.2]octanyl]methanone (30.0 mg, 0.08 mmol) in DMF (0.5 mL), NaH (1.94 mg, 0.08 mmol) was added at 0°C, and the reaction mixture was stirred for 30 minutes. [1-(trifluoromethyl)cyclopropyl]methylmethanesulfonate (26.5 mg, 0.12 mmol) was added, and the mixture was stirred at 60°C for 12 hours. The reaction mixture was quenched by adding saturated NH4Cl aqueous solution (10 mL) at 0°C, and then extracted with ELISA (10 mL x 3). The combined organic phases were washed with brine (10 mL), dried over Na2SO4, concentrated under vacuum, purified by preparative HPLC (0.225% v / v FA), and then freeze-dried to obtain the title compound (4.1 mg, 0.01 mmol, 10% yield) as a white solid. MS(ESI): m / z = 493.3 [M + H] +

[0414] Step a) [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[1-(hydroxymethyl)-4-bicyclo[2.2.2]octanyl]methanone

[0415] A solution of methyl 1-(hydroxymethyl)bicyclo[2.2.2]octane-4-carboxylate (CAS:94994-15-7) (40.0 mg, 0.2 mmol), 6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptane (A.1) (49.5 mg, 0.24 mmol), and 1,3,4,6,7,8-hexahydro-1H-pyrimido[1,2-a]pyrimidine (28.1 mg, 0.2 mmol) in THF (2 mL) was stirred at 75°C for 16 hours. The residue was concentrated under reduced pressure and purified by reverse-phase flash chromatography to obtain the title compound (43.0 mg, 0.12 mmol, yield 57.5%) as a yellow oil. MS(ESI): m / z=371.2[M+H] +

[0416] Similar to Example 155, the following examples were produced using each heteroaryl building block from step a). [Table 17]

[0417] Example 156 [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(3-ethyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone [ka]

[0418] To a solution of tert-butyl 6-(3-ethyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate (160 mg, 547 μmol) in DCM (4.45 mL), TFA (624 mg, 422 μL, 5.47 mmol) was added. The mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and the TFA was co-evaporated with toluene. The TFA salt was redissolved in DMF (4.45 mL). DIPEA (424 mg, 573 μL, 3.28 mmol) was added, followed by 4-(5-(tert-butyl)-1,2,4-oxadiazole-3-yl)benzoic acid (135 mg, 547 μmol) and 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosfinan 2,4,6-trioxide (1.39 g, 995 μL, 2.19 mmol). The mixture was stirred at room temperature for 15 hours. The mixture was diluted with ethyl acetate and washed with water. The aqueous phase was extracted twice with ethyl acetate, and the organic phase was washed with water and brine. The combined organic phase was dried over MgSO4, and the solvent was evaporated under reduced pressure. The crude material was purified by column chromatography, first eluting with DCM:methanol (10% methanol). The phase containing the product was subjected to rpHPLC for purification, yielding the title compound (49 mg, 114 μmol, 20.9% yield) as a white powder. MS(ESI): m / z = 412.3 [M + H]+ .

[0419] Step a) [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[1-(hydroxymethyl)-4-bicyclo[2.2.2]octanyl]methanone

[0420] To a solution of tert-butyl 6-((methylsulfonyl)oxy)-2-azaspiro[3.3]heptane-2-carboxylate (500 mg, 1.72 mmol) in DMF (17.2 mL), cesium carbonate (3.35 g, 10.3 mmol) was added, followed by 3-ethyl-1H-1,2,4-triazole (250 mg, 2.57 mmol). The mixture was stirred at 100°C for 24 hours. The mixture was diluted with ethyl acetate and washed with water. The aqueous phase was extracted twice with ethyl acetate, and the combined organic phase was concentrated. The crude substance was purified by SFC to obtain the title compound (160 mg, 547 μmol, yield 21.3%) as a colorless oil. MS(ESI): m / z = 293.3 [M + H] + .

[0421] Similar to Example 156, the following examples were produced using each heteroaryl building block from step a). [Table 18]

[0422] Example 173 [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-[[1-(trifluoromethyl)cyclopropyl]methoxymethyl]cyclobutyl]methanone [ka]

[0423] A solution of [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-(hydroxymethyl)cyclobutyl]methanone (30.0 mg, 0.09 mmol) in DMF (1 mL) was mixed with NaH (2.28 mg, 0.09 mmol) at 0°C and stirred for 30 minutes. Then, a solution of [1-(trifluoromethyl)cyclopropyl]methylmethanesulfonate (31.0 mg, 0.14 mmol) in DMF (1 mL) was added, and the reaction mixture was stirred at 60°C for 16 hours. The reaction mixture was quenched by adding saturated NH4Cl aqueous solution (10 mL) at 0°C. The mixture was extracted with RINKAN (10 mL x 3). The combined organic phases were washed with brine (10 mL), dried over Na₂SO₄, concentrated under vacuum, purified by preparative HPLC (0.225% v / v FA), and then freeze-dried to obtain the title compound (6.5 mg, 0.01 mmol, 15% yield) as a yellow oil. MS(ESI): m / z = 439.2 [M + H] +

[0424] Step a) [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[3-(hydroxymethyl)cyclobutyl]methanone

[0425] A solution of methyl 3-(hydroxymethyl)cyclobutane carboxylate (CAS: 89941-55-9) (60.0 mg, 0.42 mmol), 6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptane (100 mg, 0.49 mmol), and 2,3,4,6,7,8-hexahydro-1H-pyrimido[1,2-a]pyrimidine (57.93 mg, 0.42 mmol) in THF (4.25 mL) was stirred at 75°C for 16 hours. The reaction mixture was concentrated under vacuum, the residue was purified by back-flush (0.05% FA conditions), and then lyophilized to obtain the title compound (53.0 mg, 0.17 mmol, yield 40%) as a white solid. MS(ESI): m / z = 317.2 [M + H] +

[0426] Similar to Example 173, the following examples were generated using each building block from step a). [Table 19]

[0427] Example 177 (6-(3-(azetidine-1-yl)-1H-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl)(3-((4-(trifluoromethyl)benzyl)oxy)azetidine-1-yl)methanone [ka]

[0428] To a solution of (6-(3-bromo-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-(trifluoromethyl)benzyl)oxy)azetidine-1-yl)methanone (80 mg, 160 μmol) in dry DMSO (1 mL), azetidine (45.6 mg, 799 μmol), copper(I) iodide (7.61 mg, 40 μmol), L-proline (4.6 mg, 40 μmol), and Cs2CO3 (104 mg, 320 μmol) were added. The reaction mixture was then stirred at 90°C for 18 hours. Copper(I) iodide (7.61 mg, 40 μmol), L-proline (4.6 mg, 40 μmol), Cs2CO3 (104 mg, 320 μmol), and 300 mg of azetidine were added, and the reaction mixture was stirred again at 90°C for 18 hours. Insoluble matter was removed by filtration through a Celite pad, the filter pad was washed with DMSO, and the crude filtrate was directly subjected to reverse-phase HPLC purification to obtain the title compound (17.5 mg). MS(ESI): m / z = 477.3 [M + H] +

[0429] Step a) (6-(3-bromo-1H-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl)(3-((4-(trifluoromethyl)benzyl)oxy)azetidine-1-yl)methanone

[0430] Under an inert atmosphere, a suspension of di(1H-1,2,4-triazole-1-yl)methanone (471 mg, 2.87 mmol) in 6 mL of dry CH3CN cooled to 0°C was slowly added to a solution of 6-(3-bromo-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptane (A.9) (665 mg, 2.74 mmol) and DIPEA (424 mg, 573 μL, 3.28 mmol) in 8 mL of dry CH3CN. The reaction mixture was then stirred at 0°C for 5 minutes and at room temperature for 1 hour. Next, 3-((4-(trifluoromethyl)benzyl)oxy)azetidine 4-methylbenzenesulfonate (B.20) (1.27 g, 3.15 mmol) and DIPEA (707 mg, 956 μL, 5.47 mmol) were added, and the reaction mixture was stirred at 80°C for 18 hours. The reaction mixture was diluted with ethyl acetate and extracted with 1M aqueous Na2CO3 solution. The organic phase was recovered, and the aqueous phase was back-extracted with ethyl acetate. The combined organic phase was dried over sodium sulfate and evaporated to dryness. The crude material was purified by flash chromatography using a mixture of dichloromethane and methanol (0%~10%) eluates to obtain the title compound (405 mg). MS(ESI): m / z = 502.3 [M+H] +

[0431] Example 178 [6-(3-cyclopropyl-1,2,4-triazole-4-yl)-2-azaspiro[3,3]heptan-2-yl]-[rac-(3aS,6aR)-5-(2-chloro-4-fluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone [ka]

[0432] To a solution of rac-tert-butyl(3aR,6aS)-5-(2-chloro-4-fluorophenoxy)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (step c) (28.9 mg, 81.2 μmol) in DCM (1 mL), TFA (92.6 mg, 62.6 μL, 812 μmol) was added. The mixture was stirred at room temperature for 3 hours. The solvent was evaporated under reduced pressure, and TFA was co-evaporated with toluene. The TFA salt was dissolved in acetonitrile (1 mL). The mixture was cooled to 0°C. DIPEA (21 mg, 28.4 μL, 162 μmol) and 4-nitrophenyl 6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carboxylate (step b) (20 mg, 54.1 μmol) were added. The mixture was heated at 80°C for 24 hours. The solvent was removed under reduced pressure. The crude substance was purified by column chromatography using DCM / methanol (0-10% methanol) as the solvent. The title compound (4 mg, 8.23 ​​μmol, yield 15%) was obtained as a pale red solid. MS(ESI): m / z = 486.4[M+H] +

[0433] Step a) tert-butyl 6-(5-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carboxylate

[0434] To a solution of tert-butyl 6-((methylsulfonyl)oxy)-2-azaspiro[3.3]heptane-2-carboxylate (2.05 g, 7.04 mmol) in DMF (61.1 mL), cesium carbonate (8.96 g, 27.5 mmol), followed by 3-cyclopropyl-1H-1,2,4-triazole (1.00 g, 9.16 mmol) was added. The mixture was stirred at 100°C for 24 hours. The mixture was diluted with ethyl acetate and washed with water. The aqueous phase was extracted twice with ethyl acetate. The solvent was removed under reduced pressure, and the crude substance was purified by HPLC. The title compound (600 mg, 1.97 mmol, yield 22%) was obtained as a white solid. (Note: By-product obtained together with positional isomers.) MS(ESI): m / z = 305.2 [M + H] +

[0435] Step b) 4-Nitrophenyl 6-(5-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carboxylate

[0436] To a solution of tert-butyl 6-(5-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate (457 mg, 1.5 mmol) in DCM (12.2 mL), 2,2,2-trifluoroacetic acid (1.71 g, 1.15 mL, 15 mmol) was added. The mixture was stirred at room temperature for 5 hours. The solvent was removed, and the TFA was co-evaporated with toluene. The crude substance was redissolved in dry DCM (12.2 mL). The mixture was cooled to 0°C. TEA (760 mg, 1.05 mL, 7.51 mmol) was added, followed by 4-nitrophenylcarbonochloride (303 mg, 1.5 mmol). The mixture was warmed to room temperature and stirred for a further 12 hours. The solvent was removed under reduced pressure. The crude substance was purified by column chromatography using heptane / ethyl acetate (1:1) as the solvent to obtain the title compound (195 mg, 528 μmol, 35% yield) as a yellow solid. MS(ESI): m / z = 370.1[M+H] +

[0437] Step c) rac-tert-butyl(3aR,6aS)-5-(2-chloro-4-fluorophenoxy)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate

[0438] To a solution of 2-chloro-4-fluorophenol (135 mg, 100 μL, 921 μmol) in dry THF (4.61 mL), triphenylphosphine (266 mg, 1.01 mmol) was added, followed by rac-tert-butyl(3aR,6aS)-5-hydroxyhexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (CAS: 875926-93-5) (209 mg, 921 μmol). The mixture was cooled to 0°C. DIAD (205 mg, 197 μL, 1.01 mmol) was added dropwise. The mixture was warmed to room temperature and stirred for 24 hours. The reaction was stopped by adding saturated Na2CO3 aqueous solution (10 mL). The aqueous phase was extracted with DCM (3 × 20 mL). The organic phase was washed with aqueous NaOH solution (30 mL, 1 M) and brine. The organic phase was dried over MgSO4, and the solvent was evaporated under reduced pressure. The crude substance was purified by column chromatography using heptane / ethyl acetate (0.30% EA) as the solvent. The title compound (283 mg, 688 μmol, 75% yield) was obtained as a white solid. MS(ESI): m / z = 300.2 [M-Boc+H] +

[0439] Example 179 [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(2-cyclopropyloxazol-5-yl)-6-hydroxy-2-azaspiro[3,3]heptan-2-yl]methanone [ka]

[0440] To a solution of 4-(5-(tert-butyl)-1,2,4-oxadiazole-3-yl)benzoic acid (99.5 mg, 404 μmol) in DMF (1 mL), DIPEA (348 mg, 470 μL, 2.69 mmol) was added, followed by the addition of 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosfinan 2,4,6-trioxide (685 mg, 489 μL, 1.08 mmol). 6-(2-cyclopropyloxazole-5-yl)-2-azaspiro[3.3]heptan-6-ol 2,2,2-trifluoroacetate (90 mg, 269 μmol) in DMF (1 mL) was added dropwise. The reaction mixture was stirred at room temperature for 5 hours. The mixture was diluted with ethyl acetate and washed with water. The aqueous phase was extracted twice with ethyl acetate. The combined organic phases were washed with water and brine and dried over MgSO4. The solvent was evaporated under reduced pressure. The crude product was purified by rpHPLC. The title compound (17 mg, 36.4 μmol, yield 14%) was obtained as a white solid. MS(ESI): m / z = 449.3 [M + H] +

[0441] Step a) tert-butyl 6-(2-cyclopropyloxazol-5-yl)-6-hydroxy-2-azaspiro[3.3]heptan-2-carboxylate

[0442] A solution of 2-cyclopropyl oxazole (114 mg, 1.04 mmol) in anhydrous TH...

Claims

1. Equation (I) 【Chemistry 1】 (In the formula, X is CR ８ or N, A is, 【Chemistry 2】 Selected from, B is B-1 to B-6, B-9 and B-10: 【Transformation 3】 (The wavy lines indicate the connection points to the rest of equation (I).) A heteroaryl selected from, C is C ６ ~C １４ Ariel, C ３ ~C １０ Selected from cycloalkyl, 5- to 6-membered heteroaryl, and 3- to 14-membered heterocyclyl, D is C ３ ~C １０ cycloalkyl, 3- to 14-membered heterocyclyl, C ６ ~C １４ selected from aryl, and 5- to 14-membered heteroaryl, E is C ３ ~C １０ Selected from cycloalkyl and 3- to 14-membered heterocyclines, L １ is a covalent bond, -CR １２ R １３ -, -CH ２ O-, -OCH ２ -, -CH ２ NH-, -NHCH ２ -, -CH ２ OCH ２ -, -O-, -NH-, -CH ２ CH ２ -, -CH=CH-, 【Chemistry 4】 -SO ２ NH-, -NHSO ２ -, -SO ２ NHCH ２ -ien-CH ２ NHSO ２ -, -SO ２ -ien-CH ２ SO ２ -, -SO ２ CH ２ -, - (CH ２ ) ２ SO ２ -, -SO ２ (CH ２ ) ２ -, carbonyl, -NHC(O)- and -C(O)NH- are selected, L ２ This is a covalent bond, -CH ２ -ien-CH ２ NH-, -NHCH ２ -, -NH-, -N(C １ ~C ６ Alkyl)- and -SO ２ - Selected from, L ３ Covalent bonds and -CH ２ - Selected from, R １ hydrogen, halogen, 【Transformation 5】 C １ ~C ６ Alkyl, Halo-C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, Halo-C １ ~C ６ Alkoxy, C １ ~C ６ Alkyl-SO ２ NH-, C ３ ~C １０ Cycloalkyl-C １ ~C ６ Alkyl-S(O) ２ -, C １ ~C ６ Alkyl-SO ２ -, Hello-C １ ~C ６ Alkyl-S(O) ２ -, (C １ ~C ６ Alkyl) ２ N-SO ２ - and Halo-C １ ~C ６ Selected from alkyl-C(O)-, R ２ , R ３ , and R ４ These are, independently, hydrogen, halogen, and C. １ ~C ６ Alkyl, Halo-C １ ~C ６ Selected from alkyl groups and 3- to 14-membered heterocyclines, R ５ and R ６ are each independently hydrogen, halogen, cyano, hydroxy, amino, C １ to C ６ alkyl, C １ to C ６ alkoxy, halo-C １ to C ６ alkyl, halo-C １ to C ６ alkoxy, C ３ to C １０ cycloalkyl, and 3- to 14-membered heterocyclyl, and the C ３ to C １０ cycloalkyl and 3- to 14-membered heterocyclyl are optionally substituted with 1, 2 or 3 substituents selected from C １ to C ６ alkyl, halo-C １ to C ６ alkyl, C １ to C ６ alkoxy, halo-C １ to C ６ alkoxy, halogen, cyano, amino and hydroxy, R ７ It is either absent, or hydrogen, halogen, cyano, hydroxy, amino, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, Halo-C １ ~C ６ Alkyl and Halo-C １ ~C ６ Selected from alkoxy, R ８ is hydrogen, halogen, cyano, C １ ~C ６ Alkyl, C １ ~C ６ Selected from alkoxy and hydroxy, R ９ is hydrogen, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, Halo-C １ ~C ６ Alkyl, Halo-C １ ~C ６ Alkoxy, halogen, cyano, SF ５ , C １ ~C ６ Alkyl-SO ２ -, Hello-C １ ~C ６ Alkyl-SO ２ -, (C １ ~C ６ Alkyl) ２ -PO-, amino, carboxy, carboxy-C １ ~C ６ Alkyl, C １ ~C ６ Alkoxycarbonyl, C １ ~C ６ Alkoxycarbonyl-C １ ~C ６ Alkyl-, NH ２ SO ２ -, Carbamoyle, C １ ~C ６ Alkyl-C(O)NH-, Halo-C １ ~C ６ Alkyl-NHC(O)-, oxo, 【Transformation 6】 【Transformation 7】 and 【Transformation 8】 Selected from, R １０ and R １１ These are, independently, hydrogen, halogen, cyano, and C. １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, Halo-C １ ~C ６ Selected from alkyl and oxo, R １２ is hydrogen, carbamoyl, C １ ~C ６ Alkyl-NHC(O)- and Halo-C ６ ~C １４ Selected from the aryl, R １３ is hydrogen, or R １２ and R １３ Together with the carbon atoms to which they are bonded, C ３ ~C １０ Forming a cycloalkyl group, R １４ is hydrogen, C １ ~C ６ Alkyl, Halo-C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, Halo-C １ ~C ６ Alkoxy, halogen, cyano, amino, carbamoyl, hydroxy, oxo, C １ ~C ６ Alkyl-SO ２ - 【Chemistry 9】 Selected from, R １５ These are hydrogen, halogen, hydroxyl, oxo, and C. １ ~C ６ Selected from alkyl groups, R １６ It is selected from hydrogen and halogens. R １７ is hydrogen, C １ ~C ６ Alkyl and Halo-C １ ~C ６ (Selected from alkyl groups) Compounds thereof, or pharmaceutically acceptable salts thereof.

2. A, 【Chemistry 14】 Selected from, C is C ６ ~C １４ Ariel, C ３ ~C １０ Selected from cycloalkyl, 5- to 6-membered heteroaryl, and 3- to 14-membered heterocyclyl, D is C ３ ~C １０ Cycloalkyl, 3-membered to 14-membered heterocyclyl, C ６ ~C １４ Selected from aryls and 5- to 14-membered heteroaryls, E is C ３ ~C １０ Selected from cycloalkyl and 3- to 14-membered heterocyclines, L １ が, shared combination, -CR １２ R １３ -, -CH ２ O-, -CH ２ NH-, -CH ２ OCH ２ -, -O-, -NH-, 【Chemistry 15】 -SO ２ NH-, -NHSO ２ -, -SO ２ NHCH ２ -ien-CH ２ NHSO ２ -, -SO ２ -ien-CH ２ SO ２ -, - (CH ２ ) ２ SO ２ -, carbonyl, and -C(O)NH- are selected, L ２ is a covalent bond, -CH ２ -ien-CH ２ NH-, -NHCH ２ -, -NH-, -N(C １ ~C ６ Alkyl)- and -SO ２ - Selected from, L ３ However, covalent bonds and -CH ２ - Selected from, R １ but, 【Chemistry 16】 Hello C １ -C ６ Alkoxy, C １ ~C ６ Alkyl-SO ２ NH-, C ３ ~C １０ Cycloalkyl-C １ ~C ６ Alkyl-S(O) ２ -, C １ ~C ６ Alkyl-SO ２ -, Hello-C １ ~C ６ Alkyl-S(O) ２ -, (C １ ~C ６ Alkyl) ２ N-SO ２ - and Halo-C １ ~C ６ Selected from alkyl-C(O)-, R ２ However, hydrogen, halogen, C １ ~C ６ Alkyl, Halo-C １ ~C ６ Selected from alkyl groups and 3- to 14-membered heterocyclines, R ３ However, hydrogen and halogens are selected, R ４ However, it is hydrogen, R ９ However, hydrogen, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, Halo-C １ ~C ６ Alkyl, Halo-C １ ~C ６ Alkoxy, halogen, cyano, SF ５ , C １ ~C ６ Alkyl-SO ２ -, Hello-C １ ~C ６ Alkyl-SO ２ -, (C １ ~C ６ Alkyl) ２ -PO-, amino, carboxy, carboxy-C １ ~C ６ Alkyl, C １ ~C ６ Alkoxycarbonyl, C １ ~C ６ Alkoxycarbonyl-C １ ~C ６ Alkyl-, NH ２ SO ２ -, Carbamoyle, C １ ~C ６ Alkyl-C(O)NH-, Halo-C １ ~C ６ Alkyl-NHC(O)-, oxo, 【Chemistry 17】 [Chemistry 18] and 【Chemistry 19】 Selected from, C ３ ~C １０ Cycloalkyl, 3-membered to 14-membered heterocyclyl and C ６ ~C １４ Ariel is Halo-C １ ~C ６ It is optionally substituted with one or two substituents selected from alkyl, 3- to 14-membered heterocyclyl, halogen, and hydroxyl. R １０ However, hydrogen, halogen, cyano, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, Halo-C １ ~C ６ Selected from alkyl and oxo, R １１ However, hydrogen and halogens are selected, R １２ However, hydrogen, carbamoyl, C １ ~C ６ Alkyl-NHC(O)- and Halo-C ６ ~C １４ Selected from the aryl, R １３ Is it hydrogen, or R １２ and R １３ However, together with the carbon atoms to which they are bonded, C ３ ~C １０ Forming a cycloalkyl group, R １４ However, hydrogen, C １ ~C ６ Alkyl, Halo-C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, Halo-C １ ~C ６ Alkoxy, halogen, cyano, amino, carbamoyl, hydroxy, oxo, C １ ~C ６ Alkyl-SO ２ - 【Chemistry 20】 Selected from, R １５ However, hydrogen, halogens, hydroxyl, oxo, and C １ ~C ６ Selected from alkyl groups, R １６ However, hydrogen and halogens are selected, R １７ However, hydrogen, C １ ~C ６ Alkyl and Halo-C １ ~C ６ Selected from alkyl groups, A compound of formula (I) as described in claim 1, or a pharmaceutically acceptable salt thereof.

3. A, 【Chemistry 21】 A compound of formula (I) according to claim 2, or a pharmaceutically acceptable salt thereof, selected from the above.

4. A is selected from phenyl, pyridyl, azetidinyl, 2-azaspiro[3.3]heptan-2-yl, 2,6-diazaspiro[3.3]heptanyl, and 2-azaspiro[3.5]nonan-2-yl, C is C ６ ~C １４ Ariel, C ３ ~C １０ Selected from cycloalkyl and 5- to 6-membered heteroaryls, D is C ３ ~C １０ Selected from cycloalkyl and 3- to 14-membered heterocyclines, L １ is a covalent bond, -CR １２ R １３ -ien-CH ２ O-, -O-, -SO ２ NH- and -SO ２ - Selected from, L ２ However, covalent bonds and -CH ２ - Selected from, R １ but, 【Chemistry 22】 And, R ２ However, hydrogen and C １ ~C ６ Selected from alkyl groups, R ３ , R ４ , R １２ , and R １３ However, it is all hydrogen, R ９ However, halogen, C １ ~C ６ Alkyl, Halo-C １ ~C ６ Alkyl, Halo-C １ ~C ６ Alkoxy, SF ５ , C １ ~C ６ Alkyl-SO ２ - 【Chemistry 23】 【Chemistry 24】 and 【Chemistry 25】 Selected from, R １０ However, hydrogen, halogen, halo C １ ~C ６ Alkyl and C １ ~C ６ Selected from alkoxy, R １１ However, hydrogen and halogens are selected, R １４ However, hydrogen and halo-C １ ~C ６ Selected from alkyl groups, R １５ However, selected from hydrogen and hydroxyl, R １６ However, it is hydrogen. A compound of formula (I) as described in claim 2, or a pharmaceutically acceptable salt thereof.

5. A is selected from phenyl, pyridyl, azetidinyl, 2-azaspiro[3.3]heptan-2-yl, 2,6-diazaspiro[3.3]heptanyl, and 2-azaspiro[3.5]nonan-2-yl, C is selected from phenyl, cyclopropyl, pyridyl, 1,2,4-oxadiazolyl, pyrazinyl, and pyrimidinyl. D is selected from cyclopropyl, azetidinil, and pyrrolidinil. L １ is a covalent bond, -CR １２ R １３ -ien-CH ２ O-, -O-, -SO ２ NH- and -SO ２ - Selected from, L ２ However, covalent bonds and -CH ２ - Selected from, R １ but, 【Chemistry 26】 And, R ２ However, selected from hydrogen and methyl, R ３ , R ４ , R １２ , and R １３ However, it is all hydrogen, R ９ However, fluorochlorotert-butyl, CF ３ CF ３ O, SF ５ methylsulfonyl, 【Chemistry 27】 【Chemistry 28】 and 【Chemistry 29】 Selected from, R １０ However, hydrogen, fluoro, chloro, CF ３ Selected from , and methoxy, R １１ However, selected from hydrogen and fluoro, R １４ However, hydrogen and CF ３ Selected from, R １５ However, selected from hydrogen and hydroxyl, R １６ However, it is hydrogen. A compound of formula (I) as described in claim 4, or a pharmaceutically acceptable salt thereof.

6. B is B-1 to B-6, B-9 and B-10: 【Transformation 30】 (The wavy lines indicate the connection points to the rest of equation (I).) A heteroaryl selected from, R ５ However, hydrogen, halogen, cyano, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, Halo-C １ ~C ６ Alkyl, C ３ ~C １０ Selected from cycloalkyl and 3- to 14-membered heterocyclyl, the C ３ ~C １０ Cycloalkyls are hydroxy and C １ ~C ６ It is optionally substituted with one substituent selected from alkyl groups. R ６ However, hydrogen and halogens are selected, R ７ However, it does not exist, or it is hydrogen. A compound of formula (I) as described in claim 1, or a pharmaceutically acceptable salt thereof.

7. B, 【Chemistry 31】 (The wavy lines indicate the connection points to the rest of equation (I).) And, R ５ However, C １ ~C ６ Alkyl, Halo-C １ ~C ６ Alkyl and C ３ ~C １０ Selected from cycloalkyl, the C ３ ~C １０ The cycloalkyl group is optionally substituted with one hydroxyl substituent. R ６ However, it is hydrogen, R ７ However, it does not exist. A compound of formula (I) as described in claim 6, or a pharmaceutically acceptable salt thereof.

8. B, 【Chemistry 32】 (The wavy lines indicate the connection points to the rest of equation (I).) And, R ５ However, ethyl, CF ３ Selected from , and cyclopropyl, wherein the cyclopropyl is optionally substituted with one hydroxy substituent. R ６ However, it is hydrogen, R ７ However, it does not exist. A compound of formula (I) as described in claim 7, or a pharmaceutically acceptable salt thereof.

9. X is CR ８ or N, R ８ However, it is hydrogen or hydroxyl. A compound of formula (I) as described in claim 1, or a pharmaceutically acceptable salt thereof.

10. X is CR ８ And, R ８ However, it is hydrogen. A compound of formula (I) as described in claim 9, or a pharmaceutically acceptable salt thereof.

11. X is CR ８ or N, A, 【Transformation 33】 Selected from, B is B-1 to B-6, B-9 and B-10: 【Transformation 34】 (The wavy lines indicate the connection points to the rest of equation (I).) A heteroaryl selected from, C is C ６ ~C １４ Ariel, C ３ ~C １０ Selected from cycloalkyl, 5- to 6-membered heteroaryl, and 3- to 14-membered heterocyclyl, D is C ３ ~C １０ Cycloalkyl, 3-membered to 14-membered heterocyclyl, C ６ ~C １４ Selected from aryls and 5- to 14-membered heteroaryls, E is C ３ ~C １０ Selected from cycloalkyl and 3- to 14-membered heterocyclines, L １ が, shared combination, -CR １２ R １３ -, -CH ２ O-, -CH ２ NH-, -CH ２ OCH ２ -, -O-, -NH-, 【Chemistry 35】 -SO ２ NH-, -NHSO ２ -, -SO ２ NHCH ２ -ien-CH ２ NHSO ２ -, -SO ２ -ien-CH ２ SO ２ -, - (CH ２ ) ２ SO ２ -, carbonyl, and -C(O)NH- are selected, L ２ is a covalent bond, -CH ２ -ien-CH ２ NH-, -NHCH ２ -, -NH-, -N(C １ ~C ６ Alkyl)- and -SO ２ - Selected from, L ３ However, covalent bonds and -CH ２ - Selected from, R １ but, 【Transformation 36】 Hello C １ ~C ６ Alkoxy, C １ ~C ６ Alkyl-SO ２ NH-, C ３ ~C １０ Cycloalkyl-C １ ~C ６ Alkyl-S(O) ２ -, C １ ~C ６ Alkyl-SO ２ -, Hello-C １ ~C ６ Alkyl-S(O) ２ -, (C １ ~C ６ Alkyl) ２ N-SO ２ - and Halo-C １ ~C ６ Selected from alkyl-C(O)-, R ２ However, hydrogen, halogen, C １ ~C ６ Alkyl, Halo-C １ ~C ６ Selected from alkyl groups and 3- to 14-membered heterocyclines, R ３ However, hydrogen and halogens are selected, R ４ However, it is hydrogen, R ５ However, hydrogen, halogen, cyano, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, Halo-C １ ~C ６ Alkyl, C ３ ~C １０ Selected from cycloalkyl and 3- to 14-membered heterocyclyl, the C ３ ~C １０ Cycloalkyls are hydroxy and C １ ~C ６ It is optionally substituted with one substituent selected from alkyl groups. R ６ However, hydrogen and halogens are selected, R ７ However, it does not exist, or it is hydrogen. R ８ However, it is hydrogen or hydroxyl, R ９ However, hydrogen, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, Halo-C １ ~C ６ Alkyl, Halo-C １ ~C ６ Alkoxy, halogen, cyano, SF ５ , C １ ~C ６ Alkyl-SO ２ -, Hello-C １ ~C ６ Alkyl-SO ２ -, (C １ ~C ６ Alkyl) ２ -PO-, amino, carboxy, carboxy-C １ ~C ６ Alkyl, C １ ~C ６ Alkoxycarbonyl, C １ ~C ６ Alkoxycarbonyl-C １ ~C ６ Alkyl-, NH ２ SO ２ -, Carbamoyle, C １ ~C ６ Alkyl-C(O)NH-, Halo-C １ ~C ６ Alkyl-NHC(O)-, oxo, 【Chemistry 37】 【Transformation 38】 and 【Chemistry 39】 Selected from, R １０ However, hydrogen, halogen, cyano, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, Halo-C １ ~C ６ Selected from alkyl and oxo, R １１ However, hydrogen and halogens are selected, R １２ However, hydrogen, carbamoyl, C １ ~C ６ Alkyl-NHC(O)- and Halo-C ６ ~C １４ Selected from the aryl, R １３ Is it hydrogen, or R １２ and R １３ However, together with the carbon atoms to which they are bonded, C ３ ~C １０ Forming a cycloalkyl group, R １４ However, hydrogen, C １ ~C ６ Alkyl, Halo-C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, Halo-C １ ~C ６ Alkoxy, halogen, cyano, amino, carbamoyl, hydroxy, oxo, C １ ~C ６ Alkyl-SO ２ - and 【Chemistry 40】 Selected from, R １５ However, hydrogen, halogens, hydroxyl, oxo, and C １ ~C ６ Selected from alkyl groups, R １６ However, hydrogen and halogens are selected, R １７ However, hydrogen, C １ ~C ６ Alkyl and Halo-C １ ~C ６ Selected from alkyl groups, A compound of formula (I) as described in claim 1, or a pharmaceutically acceptable salt thereof.

12. X is CR ８ And, A is selected from phenyl, pyridyl, azetidinyl, 2-azaspiro[3.3]heptan-2-yl, 2,6-diazaspiro[3.3]heptanyl, and 2-azaspiro[3.5]nonan-2-yl, B, 【Chemistry 41】 (The wavy lines indicate the connection points to the rest of equation (I).) And, C is C ６ ~C １４ Ariel, C ３ ~C １０ Selected from cycloalkyl and 5- to 6-membered heteroaryls, D is C ３ ~C １０ Selected from cycloalkyl and 3- to 14-membered heterocyclines, L １ is a covalent bond, -CR １２ R １３ -ien-CH ２ O-, -O-, -SO ２ NH- and -SO ２ - Selected from, L ２ However, covalent bonds and -CH ２ - Selected from, R １ but, 【Chemistry 42】 And, R ２ However, hydrogen and C １ ~C ６ Selected from alkyl groups, R ３ , R ４ , R ６ , R ８ , R １２ and R １３ However, it is all hydrogen, R ５ However, C １ ~C ６ Alkyl, Halo-C １ ~C ６ Alkyl and C ３ ~C １０ Selected from cycloalkyl, the C ３ ~C １０ The cycloalkyl group is optionally substituted with one hydroxyl substituent. R ７ However, it does not exist. R ９ However, halogen, C １ ~C ６ Alkyl, Halo-C １ ~C ６ Alkyl, Halo-C １ ~C ６ Alkoxy, SF ５ , C １ ~C ６ Alkyl-SO ２ - 【Chemistry 43】 【Chemistry 44】 and 【Chemistry 45】 Selected from, R １０ However, hydrogen, halogen, halo C １ ~C ６ Alkyl and C １ ~C ６ Selected from alkoxy, R １１ However, hydrogen and halogens are selected, R １４ However, hydrogen and halo-C １ ~C ６ Selected from alkyl groups, R １５ However, selected from hydrogen and hydroxyl, R １６ However, it is hydrogen. A compound of formula (I) according to claim 11, or a pharmaceutically acceptable salt thereof.

13. X is CR ８ And, A is selected from phenyl, pyridyl, azetidinyl, 2-azaspiro[3.3]heptan-2-yl, 2,6-diazaspiro[3.3]heptanyl, and 2-azaspiro[3.5]nonan-2-yl, 【Chemistry 46】 (The wavy lines indicate the connection points to the rest of equation (I).) And, C is selected from phenyl, cyclopropyl, pyridyl, 1,2,4-oxadiazolyl, pyrazinyl, and pyrimidinyl. D is selected from cyclopropyl, azetidinil, and pyrrolidinil. L １ is a covalent bond, -CR １２ R １３ -ien-CH ２ O-, -O-, -SO ２ NH- and -SO ２ - Selected from, L ２ However, covalent bonds and -CH ２ - Selected from, R １ but, 【Chemistry 47】 And, R ２ However, selected from hydrogen and methyl, R ３ , R ４ , R ６ , R ８ , R １２ and R １３ However, it is all hydrogen, R ５ However, ethyl, CF ３ Selected from , and cyclopropyl, wherein the cyclopropyl is optionally substituted with one hydroxy substituent. R ７ It does not exist, R ９ However, fluorochlorotert-butyl, CF ３ CF ３ O, SF ５ methylsulfonyl, 【Chemistry 48】 【Chemistry 49】 and [Transformation 50] Selected from, R １０ However, hydrogen, fluoro, chloro, CF ３ Selected from , and methoxy, R １１ However, selected from hydrogen and fluoro, R １４ However, hydrogen and CF ３ Selected from, R １５ However, selected from hydrogen and hydroxyl, R １６ That is hydrogen. A compound of formula (I) as described in claim 12, or a pharmaceutically acceptable salt thereof.

14. (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)azetidine-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(3-((1-(trifluoromethyl)cyclopropyl)methyl)-1,2,4-oxadiazole-5-yl)azetidine-1-yl)methanone; (4-(5-(tert-butyl)-1,2,4-oxadiazole-3-yl)phenyl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (4-(5-(tert-butyl)-1,2,4-oxadiazole-3-yl)phenyl)(6-(3-(trifluoromethyl)-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-[3-(trifluoromethyl)pyrazole-1-yl]-2-azaspiro[3,3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(4-chloropyrazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(4-cyclopropylpyrazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 1-[2-[4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)benzoyl]-2-azaspiro[3,3]heptan-6-yl]pyrazole-3-carbonitriel; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-[3-(1-methylcyclopropyl)pyrazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-[5-(1-methylcyclopropyl)pyrazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(4-methoxypyrazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(4,5,6,7-tetrahydroindazole-2-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(3-methoxypyrazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(6,7-dihydro-4H-pyrano[4,3-c]pyrazole-2-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(4-fluoropyrazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-[5-(trifluoromethyl)pyrazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(5-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(6,7-dihydro-4H-pyrano[4,3-c]pyrazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(5-methoxypyrazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 1-[2-[4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)benzoyl]-2-azaspiro[3.3]heptan-6-yl]-1,2,4-triazole-3-carbonitrile; 1-[2-[4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)benzoyl]-2-azaspiro[3,3]heptan-6-yl]pyrazole-4-carbonitriel; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(4,5,6,7-tetrahydroindazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(6-methyl-3-pyridyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-methyl-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-methyl-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-fluoro-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-methyl-5-[[1-(trifluoromethyl)cyclopropyl]methoxy]pyrazine-2-yl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-fluoro-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-fluoro-6-[(1-methylcyclopropyl)methoxy]-3-pyridyl]methanone; [[6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-fluoro-6-[(1-methylcyclopropyl)methoxy]-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[[1-(trifluoromethyl)cyclopropyl]methoxy]pyrimidine-5-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-methyl-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]pyridazin-3-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(trifluoromethoxy)phenyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(1-morpholinocyclopropyl)phenyl]azetidine-1-yl]methanone; 6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(1,1-difluoroethyl)phenyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-fluoro-4-(trifluoromethoxy)phenyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(2,2,2-trifluoroethyl)phenyl]azetidine-1-yl]methanone; [3-(4-cyclopropyl-2-fluorophenyl)azetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 5-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]azetidine-3-yl]-2-(trifluoromethoxy)benzonitrile; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-methoxy-4-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; 6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[2-fluoro-4-(trifluoromethoxy)phenoxy]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[4-(trifluoromethyl)phenoxy]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-(4-tert-butylphenyl)azetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(2-chloro-4-fluorophenoxy)-2-azaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-(3-fluoro-5-(trifluoromethyl)phenoxy)-2-azaspiro[3.3]heptan-2-yl)methanone; 2-[[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]oxy]-5-(trifluoromethoxy)benzonitrile; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[2-fluoro-4-(pentafluoro-λ ６ -Sulfanyl)phenyl]methoxy]azetidine-1-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-(3,4-difluorobenzyl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((6-(trifluoromethyl)pyrazine-2-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-2-pyridyl]oxy]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-chloro-4-(trifluoromethoxy)phenyl]azetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[4-(trifluoromethoxy)phenoxy]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[2-(trifluoromethyl)pyrimidine-4-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((6-(difluoromethoxy)pyridine-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[6-(trifluoromethyl)pyrimidine-4-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[4-(trifluoromethyl)pyrimidine-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-(2,4-difluorophenoxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((6-methoxypyridine-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((2-(trifluoromethyl)pyrimidine-5-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[6-(trifluoromethyl)pyridazin-3-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((5-fluoropyridine-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (4-(5-(tert-butyl)-1,2,4-oxadiazole-3-yl)phenyl)(6-(4-cyclopropyl-1H-imidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(2,2,2-trifluoroethoxy)-2-azaspiro[3.3]heptan-2-yl]methanone; 4-[[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]oxy]-1-methylpyridine-2-one; [6-(5-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(3,4-difluorophenoxy)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-chloro-4-(trifluoromethoxy)phenyl]azetidine-1-yl]-[6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[5-(trifluoromethyl)pyrazine-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-(trifluoromethoxy)benzyl)oxy)azetidine-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-(trifluoromethyl)benzyl)oxy)azetidine-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((2-fluoro-5-(trifluoromethyl)benzyl)oxy)azetidine-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((3-fluoro-4-(trifluoromethyl)benzyl)oxy)azetidine-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((2-fluoro-4-(trifluoromethoxy)benzyl)oxy)azetidine-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((3-fluoro-5-(trifluoromethyl)benzyl)oxy)azetidine-1-yl)methanone; (3-((2-chloro-4-fluorobenzyl)oxy)azetidine-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-fluoro-2-(trifluoromethyl)benzyl)oxy)azetidine-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-(2,5-difluorophenoxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((6-(trifluoromethyl)pyridine-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((5-(trifluoromethyl)pyridine-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-((5-chloropyridine-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-((6-chloropyridine-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [3-[2-chloro-4-(trifluoromethoxy)phenyl]azetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3,5-difluoro-4-(trifluoromethoxy)phenyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-fluoro-4-(trifluoromethoxy)phenyl]azetidine-1-yl]methanone; [3-(2-tert-butylthiazole-4-yl)azetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[4-[5-(2,2-dimethylpropyl)-1,2,4-oxadiazole-3-yl]phenyl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-[2-fluoro-4-(trifluoromethyl)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(3-cyclobutyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aR,6aS)-5-(2-chloro-4-fluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-[4-(difluoromethoxy)phenyl]ethynyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aR,6aS)-5-(2-chloro-4-fluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; (3-(2-chloro-3-cyclopropylphenoxy)azetidine-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (3-(4-chloro-3-cyclopropylphenoxy)azetidine-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(2-fluoro-4-(trifluoromethyl)phenoxy)azetidine-1-yl)methanone; (3-(2-chloro-4-methylphenoxy)azetidine-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(2,4-dichlorophenoxy)azetidine-1-yl)methanone; (3-(4-chloro-2-fluorophenoxy)azetidine-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (3-((2-chloro-6-methylpyridine-3-yl)oxy)azetidine-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[3-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[4-(pentafluoro-λ ６ -Sulfanyl)phenyl]methoxy]azetidine-1-yl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[2-fluoro-4-(pentafluoro-λ ６ -Sulfanyl)phenyl]methoxy]azetidine-1-yl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[4-methyl-3-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-[2-(difluoromethyl)phenyl]ethynyl]azetidine-1-yl]methanone; [3-[(4-chloro-2-fluorophenyl)methoxy]azetidine-1-yl]-[6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[(2-chloro-4-fluorophenyl)methoxy]azetidine-1-yl]-[6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[(2,4-difluorophenyl)methoxy]azetidine-1-yl]methanone; 4-[[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]oxy]-3-fluorobenzonitrile; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-[4-(difluoromethoxy)-2-fluorophenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-[4-(trifluoromethyl)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; 2-[[rac-(3aS,6aR)-2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-5-yl]oxy]-5-(trifluoromethyl)benzonitrile; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-[3-chloro-4-(trifluoromethyl)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-[2-methoxy-4-(trifluoromethyl)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-[3-fluoro-4-(trifluoromethyl)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; 5-[[rac-(3aS,6aR)-2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-5-yl]oxy]-2-(trifluoromethyl)benzonitrile; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(3,4-difluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-[4-fluoro-3-(trifluoromethyl)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(2,4-difluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-2-methoxyphenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-2-methylsulfonylphenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(2,4,6-trifluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-3-methylphenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-3-chlorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; 2-Fluoro-5-[[rac-(3aS,6aR)-2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-5-yl]oxy]benzonitrile; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4,5-difluoro-2-methylphenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; 5-Fluoro-2-[[rac-(3aS,6aR)-2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-5-yl]oxy]benzonitrile; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-3-methylsulfonylphenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-3-methoxyphenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-[2,4-difluoro-5-(trifluoromethyl)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-[4-fluoro-3-(trifluoromethoxy)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-[4-(trifluoromethoxy)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-[3-fluoro-4-(trifluoromethoxy)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[5-(trifluoromethyl)-3-pyridyl]methoxy]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-methyl-3-[[4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-[2-(difluoromethyl)phenyl]ethynyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazole-3-yl]azetidine-1-yl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazole-3-yl]azetidine-1-yl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-methyl-6-[(1-methylcyclopropyl)methoxy]-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-methyl-6-[(1-methylcyclopropyl)methoxy]-3-pyridyl]methanone; [6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(2,2,2-trifluoroethoxy)pyrazole-1-yl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazole-2-yl]azetidine-1-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(4-methylpyrazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(4-methylpyrazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-methyl-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(3-methylpyrazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[8-[[1-(trifluoromethyl)cyclopropyl]methoxy]-5-azaspiro[2.5]octane-5-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3,3-difluoro-4-[[1-(trifluoromethyl)cyclopropyl]methoxy]-1-piperidyl]methanone; [6-(3-cyclopropylpyrazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-methyl-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone; [6-(3-cyclopropylpyrazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[5-methyl-6-(2,2,2-trifluoro-1,1-dimethylethoxy)-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-(trifluoromethyl)-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-(oxetan-3-yl)-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[4-[[1-(trifluoromethyl)cyclopropyl]methoxymethyl]-1-bicyclo[2.2.2]octanyl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(3-ethyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(4-ethylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-[4-(trifluoromethyl)imidazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(4-chloroimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 1-[2-[4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)benzoyl]-2-azaspiro[3,3]heptan-6-yl]imidazole-4-carbonitriel; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[4-[[1-(trifluoromethyl)cyclopropyl]methoxymethyl]norbornan-1-yl]methanone; [3-(5-tert-butyl-1,2,4-oxadiazole-3-yl)-1-bicyclo[1.1.1]pentanyl]-[6-(4-cyclopropylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-(5-tert-butyl-1,2,4-oxadiazole-3-yl)-1-bicyclo[1.1.1]pentanyl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[1-[1-(trifluoromethyl)cyclopropyl]triazole-4-yl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(2,2,2-trifluoroethoxy)pyrazole-1-yl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazole-5-yl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[1-[3-(trifluoromethyl)oxetane-3-yl]triazole-4-yl]azetidine-1-yl]methanone; [4-(5-tert-butyl-1,3,4-oxadiazole-2-yl)phenyl]-[6-(3-chloro-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,3,4-oxadiazole-2-yl)phenyl]-[6-(3-cyclopropylpyrazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(1-tert-butylpyrazole-4-yl)phenyl]-[6-(3-chloro-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(3-cyclopropylpyrazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(3-chloro-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[1-(trifluoromethyl)cyclopropyl]methoxymethyl]cyclobutyl]methanone; [6-(3-cyclopropylpyrazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]-[5-methyl-6-(2,2,2-trifluoro-1,1-dimethylethoxy)-3-pyridyl]methanone; [6-(3-chloro-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-methyl-6-(2,2,2-trifluoro-1,1-dimethylethoxy)-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[1-(trifluoromethyl)cyclopropyl]methoxy]cyclobutyl]methanone; (6-(3-(azetidine-1-yl)-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-(trifluoromethyl)benzyl)oxy)azetidine-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-4-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(2-chloro-4-fluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(2-cyclopropyloxazole-5-yl)-6-hydroxy-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazole-3-yl)phenyl]-[6-(5-cyclopropylpyrazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-(1-tert-butylpyrazole-4-yl)azetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-methyl-4-(trifluoromethoxy)phenyl]azetidine-1-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-cyclopropylphenoxy)azetidine-1-yl)methanone; [6-(3-cyclobutyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; (3-((3-chloro-4-cyclopropylpyridine-2-yl)oxy)azetidine-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(3-ethyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(3-cyclopropyl-4-(trifluoromethyl)phenoxy)azetidine-1-yl)methanone; 5-Cyclopropyl-2-((1-(6-(3-Cyclopropyl-1H-1,2,4-Triazole-1-yl)-2-Azaspiro[3.3]heptan-2-carbonyl)azetidine-3-yl)oxy)benzonitrile; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[2-fluoro-4-(trifluoromethyl)benzyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-cyclopropyl-2-fluorophenoxy)azetidine-1-yl)methanone; 2-Cyclopropyl-6-((1-(6-(3-Cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl)azetidine-3-yl)oxy)benzonitrile; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(3-mesylbenzyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)pyrazine-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; Methyl 3-[3-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]azetidine-3-yl]oxyphenyl]-2,2-dimethylpropanoate; N-[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]-3-(trifluoromethyl)benzenesulfonamide; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]-2-yl]-[6-[[4-fluoro-2-(trifluoromethyl)phenyl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [4-[(R)-(3-cyclopropyl-1,2,4-oxadiazole-5-yl)-(4-fluorophenyl)methyl]-1-piperidyl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(3-cyclopropyl-2-fluorophenoxy)azetidine-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; Methyl 2-[3-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]azetidine-3-yl]oxyphenyl]-2-methylpropanoate; (6-(2-chloro-4-fluorobenzyl)-2,6-diazaspiro[3.3]heptan-2-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-(trifluoromethyl)phenoxy)azetidine-1-yl)methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(3-isopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-cyclopropyl-3-fluoropyridine-2-yl)oxy)azetidine-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(4-mesylbenzyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[3-hydroxy-3-(trifluoromethyl)azetidine-1-yl]-3-pyridyl]azetidine-1-yl]methanone; (4-((3-cyclopropyl-1,2,4-oxadiazole-5-yl)(4-fluorophenyl)methyl)piperidine-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((6-cyclopropyl-2-fluoropyridine-3-yl)oxy)azetidine-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[3-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [3-[(5-cyclopropyl-2-pyridyl)oxy]azetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((4-fluoro-2-(trifluoromethyl)phenyl)sulfonyl)-2,6-diazaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[3-hydroxy-3-(trifluoromethyl)pyrrolidino]-3-pyridyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(3,5-difluorophenyl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(3R)-3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-yl]methanone; N-[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]-2,2-dimethylpropane-1-sulfonamide; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(3S)-3-hydroxy-3-(trifluoromethyl)pyrrolidino]-3-pyridyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(5-fluoro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(4-methylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(2-methoxy-3-(trifluoromethyl)phenoxy)azetidine-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(3-cyclopropyl-4-fluorophenoxy)azetidine-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(3,5-difluorobenzyl)-2,6-diazaspiro[3.3]heptan-2-yl]methanone; (3-(2-chloro-3-(trifluoromethyl)phenoxy)azetidine-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; (2-cyclohexylsulfonyl-2,6-diazaspiro[3.3]heptan-6-yl)-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[4-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[3-fluoro-5-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [4-[(S)-(3-cyclopropyl-1,2,4-oxadiazole-5-yl)-(4-fluorophenyl)methyl]-1-piperidyl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-((2-chloro-4-fluorophenyl)sulfonyl)-2,6-diazaspiro[3.3]heptan-2-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; 2-[[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methyl]methyl benzoate; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[4-(trifluoromethoxy)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(2,4-difluorophenyl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[3-(trifluoromethoxy)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(2,4-difluorobenzyl)-2,6-diazaspiro[3.3]heptan-2-yl]methanone; (3-((4-chloro-5-cyclopropylpyridine-3-yl)oxy)azetidine-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[4-fluoro-3-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-(2-piperidinosulfonyl-2,6-diazaspiro[3.3]heptan-6-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-(4-fluoro-2-mesylphenoxy)-2-azaspiro[3.5]nonane-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-(2-neopentylsulfonyl-2,6-diazaspiro[3.3]heptan-6-yl)methanone; 2-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzonitrile; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(2-fluoro-4-methylphenoxy)azetidine-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(2,4,6-trifluorophenyl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [2-[(2-chloro-3-pyridyl)sulfonyl]-2,6-diazaspiro[3.3]heptan-6-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [2-(cyclohexylmethylsulfonyl)-2,6-diazaspiro[3.3]heptan-6-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(3-methoxyphenyl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; N-[[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]azetidine-3-yl]methyl]-3-(trifluoromethyl)benzenesulfonamide; 6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-N-[[1-(trifluoromethyl)cyclopropyl]methyl]-2,6-diazaspiro[3.3]heptan-2-sulfonamide; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((6-(trifluoromethyl)pyridazine-3-yl)oxy)azetidine-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-((1,1,1-trifluoropropane-2-yl)oxy)-1H-pyrazole-1-yl)azetidine-1-yl)methanone; (2-benzofurazan-4-ylsulfonyl-2,6-diazaspiro[3.3]heptan-6-yl)-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(2-methoxyphenyl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-[1-(2H-tetrazole-5-yl)cyclopropyl]phenyl]azetidine-1-yl]methanone; N-[[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-4-piperidyl]methyl]-4-(trifluoromethyl)benzenesulfonamide; (3-((6-chloro-5-cyclopropylpyridine-3-yl)oxy)azetidine-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[[6-(trifluoromethyl)-3-pyridyl]sulfonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methanone; 6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-N-(4-fluorobenzyl)-2,6-diazaspiro[3.3]heptan-2-sulfonamide; 2-[[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methyl]benzenesulfonamide; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(3,5-difluoro-2-pyridyl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; N-[[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-4-piperidyl]methyl]-4-(trifluoromethoxy)benzenesulfonamide; 6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-N-[1-(trifluoromethyl)cyclopropyl]-2,6-diazaspiro[3.3]heptan-2-sulfonamide; 4-(1-(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl)azetidine-3-yl)-1-(2,2,2-trifluoroethyl)pyridine-2(1H)-one; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[2-fluoro-4-(trifluoromethyl)benzyl]amino]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[[4-(trifluoromethyl)-3-pyridyl]sulfonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methanone; 2-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]methyl benzoate; (2-benzylsulfonyl-2,6-diazaspiro[3.3]heptan-6-yl)-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-(2-fluoro-4-mesyl-benzyl)oxyazetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[6-(trifluoromethyl)pyridazine-3-yl]amino]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[[5-(trifluoromethyl)-3-pyridyl]sulfonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methanone; 6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-N-(1-methylcyclopropyl)-2,6-diazaspiro[3.3]heptan-2-sulfonamide; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((6-(trifluoromethyl)pyridine-3-yl)oxy)azetidine-1-yl)methanone; 4-Chloro-N-[[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-4-piperidyl]methyl]benzenesulfonamide; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[2-(4-fluorophenyl)ethylsulfonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(3,4-difluorophenyl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((2-cyclopropylpyrimidine-4-yl)oxy)azetidine-1-yl)methanone; (6-(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)(4-fluoro-2-(trifluoromethyl)phenyl)methanone; N-[[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]azetidine-3-yl]methyl]-4-(trifluoromethyl)benzenesulfonamide; N-[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]-1-(trifluoromethyl)cyclopropanecarboxamide; [2-[(4-chloro-3-pyridyl)sulfonyl]-2,6-diazaspiro[3.3]heptan-6-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 2-[3-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]azetidine-3-yl]oxyphenyl]-2-methylpropanoic acid; [3-(6-cyclopropylpyridazin-3-yl)oxyazetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(3,5-dimethylisoxazole-4-yl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(4-methoxyphenyl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((2-(trifluoromethyl)pyrimidine-4-yl)oxy)azetidine-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-(2-pyrrolidinosulfonyl-2,6-diazaspiro[3.3]heptan-6-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((6-(trifluoromethyl)pyrimidine-4-yl)oxy)azetidine-1-yl)methanone; [2-[(6-chloro-2-pyridyl)sulfonyl]-2,6-diazaspiro[3.3]heptan-6-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 3-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzonitrile; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(1-methylcyclopropyl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(5-(2,4-difluorophenyl)-4H-1,2,4-triazole-3-yl)azetidine-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(4-fluoro-2-methoxyphenyl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; (2S)-2-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-4-piperidyl]-2-(4-fluorophenyl)acetamide; (6-(2-chloro-4-fluorobenzoyl)-2,6-diazaspiro[3.3]heptan-2-yl)(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; 4-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]azetidine-3-yl]benzenesulfonamide; 3-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]-4-fluorobenzamide; N-[4-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]phenyl]acetamide; [2-(cyclopropylmethylsulfonyl)-2,6-diazaspiro[3.3]heptan-6-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[[2-(trifluoromethyl)-3-pyridyl]sulfonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methanone; 4-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzamide; 3-[3-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]azetidine-3-yl]oxyphenyl]-2,2-dimethylpropanoic acid; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(5-methylisoxazole-4-yl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; (2R)-2-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-4-piperidyl]-2-(4-fluorophenyl)acetamide; N-[[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]azetidine-3-yl]methyl]-4-fluoro-2-(trifluoromethyl)benzenesulfonamide; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((6-(trifluoromethyl)pyrazine-2-yl)oxy)azetidine-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-(2-trifuryl-2,6-diazaspiro[3.3]heptan-6-yl)methanone; 2-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]-4-piperidyl]-2-(4-fluorophenyl)acetamide; (2S)-2-[4-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]piperazino]-2-(4-fluorophenyl)acetamide; [3-[[4-(Pentafluoro-λ ６ -Sulfanyl)phenyl]methoxy]azetidine-1-yl]-[6-[4-(trifluoromethyl)imidazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; 4-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzonitrile; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[(2-methoxy-3-pyridyl)sulfonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [2-(2-aminopyrimidine-5-yl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 2-[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]-N-methyl-2-phenylacetamide; 1-(1-(6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl)azetidine-3-yl)-N-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carboxamide; 2-[[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methyl]benzoic acid; 6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-N,N-dimethyl-2,6-diazaspiro[3.3]heptan-2-sulfonamide; [6-(4-methylimidazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[4-(pentafluoro-λ ６ -Sulfanyl)phenyl]methoxy]azetidine-1-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-(trifluoromethyl)pyrimidine-2-yl)oxy)azetidine-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(3-pyridylsulfonyl)-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-(2-morpholinosulfonyl-2,6-diazaspiro[3.3]heptan-6-yl)methanone; 3-[[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-4-piperidyl]methyl]-4-fluorobenzenesulfonamide; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-(2-propylsulfonyl-2,6-diazaspiro[3.3]heptan-6-yl)methanone; N-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-4-piperidyl]-4-(trifluoromethyl)benzenesulfonamide; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(trifluoromethyl)pyridazine-3-yl]oxyazetidine-1-yl]methanone; 2-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzamide; 4-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzoic acid; N-[[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-4-piperidyl]methyl]benzenesulfonamide; (2R)-2-[4-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]piperazino]-2-(4-fluorophenyl)acetamide; 3-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]-4-fluorobenzoic acid; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(5-ethyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(2,2,2-trifluoroethylsulfonyl)-2,6-diazaspiro[3.3]heptan-6-yl]methanone; (2S)-2-[4-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]piperazino]-2-(4-fluorophenyl)-N-methylacetamide; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(1-methylpyrazole-4-yl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; 2-[4-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]piperazino]-2-(4-fluorophenyl)acetamide; (6-(3-cyclopropyl-1H-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(5-(cyclopropylmethyl)-4H-1,2,4-triazole-3-yl)azetidine-1-yl)methanone; 2-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]-N-methyl-benzamide; (2R)-2-[4-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]piperazino]-2-(4-fluorophenyl)-N-methylacetamide; N-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-4-piperidyl]-4-fluorobenzenesulfonamide; 1-[2-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]-2,2,2-trifluoroethanone; 2-[[6-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzoic acid; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(1,1-diketothietan-3-yl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; 2-[4-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]piperazino]-2-(4-fluorophenyl)-N-methylacetamide; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[6-(triazole-2-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[6-(triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(4-fluorophenyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[6-[2-(trifluoromethyl)pyrimidine-5-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[4-(trifluoromethylsulfonyl)phenyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(4-methylsulfonylphenyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-chloro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(5-fluoro-3-pyridyl)-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [3-[4-[3-(2,2-dimethylpropyl)triazole-4-yl]phenyl]azetidine-1-yl]-[6-(5-fluoro-3-pyridyl)-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[6-(5-fluoro-3-pyridyl)-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[(6S)-6-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[(6R)-6-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[4-fluoro-2-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-(5-cyclopropyl-3-methylpyrazole-1-yl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-(5-cyclopropyl-3-methylpyrazole-1-yl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-(3,5-dimethylpyrazole-1-yl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(1H-pyrazolo[4,3-b]pyridine-5-ylmethyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-methylsulfonyl-5-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[(6S)-6-[[3-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[(6R)-6-[[3-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[(6S)-6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[(6R)-6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [6-[(4-cyclopropylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; 5-[[2-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]-2-(trifluoromethyl)benzonitrile; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[6-(5-fluoro-3-pyridyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-chloro-3-fluoro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; 4-[[2-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]-2-(trifluoromethyl)benzonitrile; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[7-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2,7-diazaspiro[3.4]octan-2-yl]methanone; 3-[[2-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]-5-(trifluoromethyl)benzonitrile; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-3-pyridyl]azetidine-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(3R)-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(4-dimethylphosphorylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-dimethylphosphorylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-dimethylphosphoryl-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(5-dimethylphosphoryl-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(4-dimethylphosphorylphenyl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(5-fluoro-3-pyridyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[6-(trifluoromethoxy)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[[6-(trifluoromethyl)-3-pyridyl]methyl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-(1H-pyrazolo[4,3-b]pyridine-5-ylmethyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[(5-cyclopropyl-4H-1,2,4-triazole-3-yl)methyl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-methylsulfonyl-3-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-(4-chloro-2-methylsulfonylphenyl)-3-pyridyl]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; 5-[[(6S)-2-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.4]octane-6-yl]oxy]-2-(trifluoromethyl)pyridine-4-carbonitriel; [6-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3.4]octan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [6-[(5-fluoro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2,7-diazaspiro[3.5]nonane-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[7-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2,7-diazaspiro[3.5]nonane-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[[2-methoxy-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[4-[5-[(1-methylcyclopropyl)methyl]-4H-1,2,4-triazole-3-yl]phenyl]azetidine-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[[1-(trifluoromethyl)cyclopropyl]methylamino]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(3S)-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidine-1-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[[4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidine-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)-2-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; N-[2-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]-3-(trifluoromethyl)benzenesulfonamide; [6-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(2-fluoro-4-methylsulfonyl-phenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-chloro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[6-(trifluoromethyl)pyridazin-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(trifluoromethyl)pyrimidine-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(3-fluoro-5-methylsulfonyl-phenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[6-(1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[(4-dimethylphosphorylphenyl)methoxy]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[(4-dimethylphosphorylphenyl)methoxy]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-fluoro-2-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[4-[3-(2,2-dimethylpropyl)triazole-4-yl]phenyl]azetidine-1-yl]-[6-(1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-[5-[1-(trifluoromethyl)cyclopropyl]-4H-1,2,4-triazole-3-yl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[5-[1-(trifluoromethyl)cyclopropyl]-4H-1,2,4-triazole-3-yl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; [3-[3-[[[1-(trifluoromethyl)cyclopropyl]amino]methyl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-[[1-(trifluoromethyl)cyclopropyl]methylamino]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-[3-(trifluoromethyl)azetidine-1-yl]-3-pyridyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[2-[3-(trifluoromethyl)azetidine-1-yl]pyrimidine-5-yl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-3-pyridyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[4-[5-[(1-methylcyclopropyl)methyl]-4H-1,2,4-triazole-3-yl]phenyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-[(3S)-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-[(3R)-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-[(1,1-dioxothietan-3-yl)methylamino]-3-pyridyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; 2-[4-[1-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3,3]heptan-2-carbonyl]azetidine-3-yl]phenyl]benzamide; [6-[[4-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-(5-cyclopropyl-4H-1,2,4-triazole-3-yl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; [3-[3-(5-cyclopropyl-4H-1,2,4-triazole-3-yl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2,7-diazaspiro[3.4]octan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazole-2-yl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; [3-[3-(5-cyclopropyl-1,3,4-oxadiazole-2-yl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(trifluoromethyl)pyrazine-2-yl]methyl]-2,7-diazaspiro[3.4]octan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[6-(trifluoromethyl)pyridazine-3-yl]methyl]-2,7-diazaspiro[3.4]octan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2,7-diazaspiro[3.4]octan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[[[1-(trifluoromethyl)cyclopropyl]amino]methyl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[[1-(trifluoromethyl)cyclopropyl]methylamino]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-[5-[(1-methylcyclopropyl)methyl]-4H-1,2,4-triazole-3-yl]phenyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(5-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[[2-methoxy-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-[3-hydroxy-3-(trifluoromethyl)azetidine-1-yl]-3-pyridyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-(3-hydroxy-3-methylazetidine-1-yl)-3-pyridyl]azetidine-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; 3-(trifluoromethyl)-N-[2-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]benzenesulfonamide; [6-[(4-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(3-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-methylsulfonyl-3-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-methylsulfonyl-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(2-fluoro-4-methylsulfonyl-phenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(3-fluoro-5-methylsulfonyl-phenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2,7-diazaspiro[3.5]nonane-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2,7-diazaspiro[3.5]nonane-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[[3-(trifluoromethyl)oxetane-3-yl]amino]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-[5-[1-(trifluoromethyl)cyclopropyl]-4H-1,2,4-triazole-3-yl]phenyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(5-cyclopropyl-1H-1,2,4-triazole-3-yl)phenyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(3-fluoro-5-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[5-[[1-(trifluoromethyl)cyclopropyl]methylamino]pyrazine-2-yl]azetidine-1-yl]methanone; [3-[4-(5-cyclobutyl-1H-1,2,4-triazole-3-yl)phenyl]azetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[6-(trifluoromethyl)pyridazin-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)pyrazine-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[[3-(trifluoromethyl)-1-bicyclo[1.1.1]pentanyl]sulfonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-fluoro-2-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(3S)-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[[1-(trifluoromethyl)cyclopropyl]amino]-3-pyridyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[5-[[1-(trifluoromethyl)cyclopropyl]methylamino]-2-pyridyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-[3-(trifluoromethyl)azetidine-1-yl]pyrimidine-5-yl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(3S)-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-[(3S)-3-(trifluoromethyl)pyrrolidine-1-yl]pyrimidine-5-yl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-[(3R)-3-(trifluoromethyl)pyrrolidine-1-yl]pyrimidine-5-yl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(2-fluoro-4-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[3-(trifluoromethyl)-1-bicyclo[1.1.1]pentanyl]sulfonyl]-2,7-diazaspiro[3.5]nonane-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[(3-methylsulfonylphenyl)methyl]-2,7-diazaspiro[3.5]nonane-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[(4-methylsulfonylphenyl)methyl]-2,7-diazaspiro[3.5]nonane-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)pyrazine-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(5-methylsulfonyl-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(5-methylsulfonyl-3-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[(3-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[[1-(trifluoromethyl)cyclopropyl]amino]-3-pyridyl]azetidine-1-yl]methanone; (2R)-1-[4-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]azetidine-3-yl]phenyl]-4,4-difluoropiperidine-2-carboxamide; (2R)-1-[4-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]azetidine-3-yl]phenyl]-4,4-difluoropiperidine-2-carboxamide; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[3-(trifluoromethyl)azetidine-1-yl]-3-pyridyl]azetidine-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazole-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[2-[3-(trifluoromethoxy)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[3-(trifluoromethylsulfonyl)phenyl]methoxy]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-methylsulfonylphenyl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(3-methylsulfonylphenyl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(2-methylsulfonylphenyl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; 1-[4-[1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-carbonyl]azetidine-3-yl]phenyl]-4,4-difluoropiperidine-2-carboxamide; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-(3-hydroxy-3-methylazetidine-1-yl)-3-pyridyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(1,1-dioxothiolan-3-yl)amino]-3-pyridyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[4-(3-fluorophenoxy)-1-piperidyl]methanone; [3-(4-cyclobutylphenyl)azetidine-1-yl]-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-(2-fluoro-6-methylphenyl)ethyl]azetidine-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[(E)-2-(3-fluorophenyl)vinyl]azetidine-1-yl]methanone; Bis[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3,3]heptan-2-yl]methanone; [7-[[6-(difluoromethoxy)-3-pyridyl]methyl]-2-azaspiro[3.5]nonan-2-yl]-[6-(5-fluoro-3-pyridyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-cyclopropyl-4-(trifluoromethyl)phenoxy]azetidine-1-yl]-[6-(5-fluoro-3-pyridyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[(2-chloro-4-fluorophenyl)methoxy]azetidine-1-yl]-[6-(5-fluoro-3-pyridyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[[2-chloro-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[6-(5-fluoro-3-pyridyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(5-fluoro-3-pyridyl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [7-[(5-fluoro-2-pyridyl)methyl]-2-azaspiro[3.5]nonan-2-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [7-[(5-chloro-2-pyridyl)methyl]-2-azaspiro[3.5]nonan-2-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[[2-methoxy-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(trifluoromethyl)pyrazine-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]-[3[[4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidine-1-yl]methanone; [7-[[6-(difluoromethoxy)-3-pyridyl]methyl]-2-azaspiro[3.5]nonan-2-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; Bis[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3,3]heptan-2-yl]methanone; [3-[6-[3-(trifluoromethyl)azetidine-1-yl]-3-pyridyl]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[6-(trifluoromethyl)-3-pyridyl]oxy]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [3-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-3-pyridyl]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-cyclopropyl-4-(trifluoromethyl)phenoxy]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(3-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(4-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[[2-chloro-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[4-methylsulfonyl-3-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[(2-chloro-4-fluorophenyl)methoxy]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-(4-isopropyl-N-methyl-anilino)-3-pyridyl]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; 2-(trifluoromethyl)-5-[[2-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]benzonitrile; [3-[5-(2,4-dichlorophenyl)-2-pyridyl]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-(2-chloro-4-methylsulfonylphenyl)-3-pyridyl]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; and [3-[5-(4-chloro-2-fluorophenyl)-2-pyridyl]azetidine-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone Selected from, A compound of formula (I) as described in claim 1, or a pharmaceutically acceptable salt thereof.

15. A compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof, for use as a therapeutically active substance.

16. A pharmaceutical composition comprising a compound of formula (I) as described in claim 1 or a pharmaceutically acceptable salt thereof, and a therapeutically inactive carrier.

17. The pharmaceutical composition according to claim 16, for use in the treatment or prevention of neuroinflammation, neurodegenerative diseases, pain, cancer, mental disorders, and / or inflammatory bowel disease in mammals.

18. The pharmaceutical composition according to claim 17, wherein the neuroinflammation, neurodegenerative disease, pain, cancer, and mental disorder are selected from multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, anxiety, migraine, depression, hepatocellular carcinoma, colon carcinogenesis, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, pain-associated spasticity, abdominal pain, abdominal pain associated with irritable bowel syndrome, and / or visceral pain.

Images