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 THE INVENTION The present invention relates to organic compounds useful for the treatment or prevention in mammals, in particular monoacylglycerol lipase (MAGL) inhibitors for the treatment or prevention of neuroinflammation, neurodegenerative diseases, pain, cancer, psychiatric disorders, multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, anxiety, migraine, 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 their biological effects by interacting with cannabinoid receptors (CBRs), CB1 and CB2. They regulate multiple 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 diacylglycerol lipase (DAGL) and hydrolyzed by monoacylglycerol lipase MAGL. MAGL hydrolyzes 85% of 2-AG, while the remaining 15% is hydrolyzed by ABHD6 and ABDH12 (Nomura, DK, et al., Science 2011, 334, 809). MAGL is expressed throughout the brain and in most brain cell types, including neurons, astrocytes, oligodendrocytes, and microglial cells (Chanda, P.K., 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 (PGs) and leukotrienes (LTs). AA oxidative metabolism is increased in inflamed tissues. Two major enzymatic pathways for arachidonic acid oxidation involved in the inflammatory process include cyclooxygenase, which produces PGs, and 5-lipoxygenase, which produces LTs. Among the various cyclooxygenase products formed during inflammation, PGE2 is one of the most important. These products have been detected at sites of inflammation, 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- / -) exhibit a dramatic decrease in 2-AG hydrolase activity and a dramatic increase in 2-AG levels in the nervous system, whereas other arachidonoyl-containing phospholipids and neutral lipid species, including anandamide (AEA), and other free fatty acids, are 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 greatly reduced. Although the phospholipase A2 (PLA2) enzyme has been considered the major source of AA, cPLA2-deficient mice have unchanged AA levels in their brains, highlighting the importance of MAGL's role in the regulation of AA production and brain inflammatory processes.

[0003] Neuroinflammation is a common pathological feature of 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 psychiatric disorders such as anxiety and migraine). In the brain, the production of eicosanoids and prostaglandins regulates the neuroinflammatory process. The inflammatory progenitor lipopolysaccharide (LPS) produces a robust, time-dependent increase in brain eicosanoids that is significantly blunted in Mgll- / - mice. LPS treatment also induces a widespread increase in inflammatory cytokines, including interleukin-1-a (IL-1-a), IL-1b, IL-6, and tumor necrosis factor-a (TNF-a), 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 the progression of diseases, 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 have been widely used in preclinical models of neuroinflammation and neurodegeneration (Long, JZ, et al., Nature Chemical Biology 2009, 5, 37). Systemic injection of such inhibitors recapitulates the Mgll- / - mouse phenotype in the brain, including increased 2-AG levels, decreased AA levels and related eicosanoid production, and suppression of cytokine production and microglial activation after LPS-induced neuroinflammation (Nomura, DK, et al., Science 2011, 334, 809), confirming MAGL as a druggable target.

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

[0007] Furthermore, oligodendrocytes (OLs) and their precursors (OPCs), myelinating cells in the central nervous system, express cannabinoid receptor 2 (CB2) on their membranes. 2-AG is an endogenous ligand for both CB1 and CB2 receptors. It has been reported that both cannabinoids and pharmacological inhibition of MAGL attenuate the vulnerability of OLs and OPCs to excitotoxic injury and may therefore be neuroprotective (Bernal-Chico, A., et al., Glia 2015, 63, 163). Additionally, pharmacological inhibition of MAGL increases the number of myelinating OLs in the mouse brain, suggesting that MAGL inhibition may promote OPC differentiation into myelinating 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, especially lipid metabolism, has recently been given great importance in cancer research. Researchers believe that de novo fatty acid synthesis plays an important role in tumor development. Many studies have shown that endocannabinoids have antitumor effects, including antiproliferative, apoptosis-inducing, and anti-metastatic effects. MAGL, as a key degradative enzyme for both lipid metabolism and the endocannabinoid system, further contributes to various aspects of tumorigenesis, including glioblastoma, as part of gene expression profiles (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 endocannabinoid system is also involved in many gastrointestinal physiological and physiopathological functions (Marquez, Suarez et al. 2009). All of these effects are primarily driven through cannabinoid receptors (CB1 and CB2), CB1 receptors. CB1 receptors are present throughout the gastrointestinal tract in animals and healthy humans, particularly in the enteric nervous system (ENS) and epithelial lining, as well as in smooth muscle cells of blood vessels in the colon wall (Wright, Rooney et al. 2005, Duncan, Davison et al. 2005). CB1 activation provides antiemetic, antimotility, and anti-inflammatory effects and helps regulate pain (Perisetti, Rimu et al. 2020). CB2 receptors are expressed in immune cells such as plasma cells and macrophages, the lamina propria of the gastrointestinal tract (Wright, Rooney et al. 2005), and the epithelium of human colonic tissue, primarily associated with inflammatory bowel disease (IBD). CB2 activation exerts anti-inflammatory effects by reducing pro-inflammatory cytokines. MAGL expression is increased in colonic tissues 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 murine 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). Summary of the Invention [Problem to be solved by the invention]

[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 providing 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 aspect, the present invention provides a compound of formula (I) [ka] (Wherein A, B, X and R 1 ~R 7 is as defined herein) The present invention provides a compound of the formula:

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

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

[0014] In a further aspect, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for use as a therapeutically active substance.

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

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

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

[0018] In a further aspect, the present invention provides a compound of formula (I), as described herein, or a pharmaceutically acceptable salt 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 carcinogenesis, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, spasticity associated with pain, abdominal pain, abdominal pain associated with irritable bowel syndrome, and / or visceral pain in a mammal. DETAILED DESCRIPTION OF THE INVENTION

[0019] Detailed Description of the Invention definition It should be understood that any feature, integer, characteristic, compound, chemical moiety, or group described in connection with a particular aspect, embodiment, or example of the invention is applicable to any other aspect, embodiment, or example described herein, except where inconsistent therewith. All features disclosed in this specification (including any accompanying claims, abstract, and drawings), and / or all steps of any method or process so disclosed, may be combined in any combination, except combinations in which at least some of such features and / or steps are mutually exclusive. The invention is not limited to the details of any of the foregoing embodiments. The invention extends to any novel or any novel combination of features disclosed in this specification (including any accompanying claims, abstract, and drawings), or any novel or any novel combination of steps of any method or process so disclosed.

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

[0021] The term "alkoxy" refers to an alkyl group, as defined above, attached to the parent molecular moiety through an oxygen atom. An alkoxy group contains 1 to 12 carbon atoms, unless otherwise specified. In some preferred embodiments, an alkoxy group contains 1 to 6 carbon atoms ("C 1~6In other embodiments, alkoxy groups contain 1 to 4 carbon atoms. In yet other embodiments, alkoxy groups contain 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 alkoxy is methoxy.

[0022] The term "halogen" or "halo" refers to fluoro (F), chloro (Cl), bromo (Br), or iodo (I). Preferably, the term "halogen" or "halo" refers 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] The term "cycloalkyl" as used herein refers to a saturated or partially unsaturated, monocyclic or bicyclic hydrocarbon group of 3 to 10 ring carbon atoms ("C 3-10 In some preferred embodiments, the cycloalkyl group is a saturated monocyclic hydrocarbon group of 3 to 8 ring carbon atoms. "Bicyclic cycloalkyl" refers to a cycloalkyl moiety consisting of two saturated carbocyclic rings having two common carbon atoms, i.e., the bridge 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 joined through one common ring atom. Preferably, the cycloalkyl group is a saturated monocyclic hydrocarbon group of 3 to 6 ring carbon atoms, e.g., 3, 4, 5, or 6 carbon atoms. Some non-limiting examples of cycloalkyl 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 cycloalkyl is cyclopropyl.

[0024] The term "aryl" refers to a group having a total of 6 to 14 ring members ("C6-C14 Aryl) is preferably a monocyclic, bicyclic, or tricyclic carbocyclic ring system having 6 to 12 ring members, more preferably 6 to 10 ring members, in which at least one ring of the system is aromatic. Some non-limiting examples of aryl include phenyl and 9H-fluorenyl (e.g., 9H-fluoren-9-yl). A particularly preferred, but non-limiting example of aryl is phenyl.

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

[0026] The term "heteroaryl" refers to a mono- 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, and 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-limiting examples of heteroaryls include spiro[cyclopropane-1,3′-indoline] (e.g., spiro[cyclopropane-1,3′-indoline]-1′-yl), 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazin-2-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrimidin-6-yl, indol-1-yl, 1H-indol-2-yl, 1H-indol-3-yl, 1H-indol-4-yl, 1H-indol-5-yl, 1H-indol-6-yl, 1H-indol-8-yl, 1H-indol-9-yl, 1H-indol-10-yl, 1H-indol-11-yl, 1H-indol-12-yl, 1H-indol-13-yl, 1H-indol-14-yl, 1H-indol-15-yl, 1H-indol-16-yl, 1H-indol-17-yl, 1H-indol-18-yl, 1H-indol-19 ... 1H-indol-4-yl, 1H-indol-5-yl, 1H-indol-6-yl, 1H-indol-7-yl, 1,2-benzoxazol-3-yl, 1,2-benzoxazol-4-yl, 1,2-benzoxazol-5-yl, 1,2-benzoxazol-6-yl, 1,2-benzoxazol-7-yl, 1H-indazol-3-yl, 1H-indazol-4-yl, 1H-indazol-5-yl, 1H-indazol-6-yl, 1H-indazol 7-indazol, pyrazol-1-yl, 1H-pyrazol-3-yl, 1H-pyrazol-4-yl, 1H-pyrazol-5-yl, imidazol-1-yl, 1H-imidazol-2-yl, 1H-imidazol-4-yl, 1H-imidazol-5-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, thiazol-2-yl, thiazole 4-yl, thiazol-5-yl, pyridazin-3-yl, pyridazin-4-yl, 1,2,4-triazol-4-yl, 1,2,4-triazol-1-yl, 4H-1,2,4-triazol-3-yl, 4,5,6,7-tetrahydroindazol-2-yl, 6,7-dihydro-4H-pyrano[4,3-c]pyrazol-2-yl, thiazolyl, benzofuran-4-yl, tetrathiazolyl, isoxazolyl, and morpholinyl. Particularly preferred, but non-limiting examples of heteroaryl include pyridyl, pyrazinyl, pyrimidinyl, pyrazolyl, imidazolyl, oxazolyl, oxadiazolyl, and triazolyl.

[0027] The term "heterocyclyl" refers to a saturated or partially unsaturated monocyclic or bicyclic, preferably monocyclic, ring system of 3 to 14 ring atoms, preferably 3 to 10 ring atoms, more preferably 3 to 8 ring atoms, in which 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. "Bicyclic heterocyclyl" refers to a heterocyclic moiety consisting of two rings having two ring atoms in common, i.e., the bridge separating the two rings is either a single bond or a chain of one or two ring atoms, and a spirocyclic moiety, i.e., the two rings are joined via one common ring atom. 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]pyrrol-2-yl, 2-azaspiro[3.3]heptan-2-yl, 2,6-diazaspiro[3.3]heptanyl, 2-azaspiro[3.5]nonan-2-yl, 1,2-dihydropyridin, piperidyl, pyrrolidinyl, tetrahydrothiophenyl, and thietanyl.

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

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

[0030] The term "amino" refers to the group --NH.sub.2.

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

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

[0033] The term "oxo" refers to a 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 fluoro. Preferably, "haloalkyl" refers to an alkyl group in which one, two, or three hydrogen atoms of the alkyl group are replaced by halogen atoms, most preferably fluoro. Particularly preferred, but non-limiting, examples of haloalkyl 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 alkoxy group's hydrogen atoms has been replaced with a halogen atom, preferably fluoro. Preferably, "haloalkoxy" refers to an alkoxy group in which one, two, or three of the alkoxy group's hydrogen atoms have been replaced with a halogen atom, most preferably fluoro. Particularly preferred, but non-limiting, examples of haloalkoxy are trifluoromethoxy, difluoromethoxy, 2,2,2-trifluoro-1,1-dimethyl-ethoxy, (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 effectiveness and properties of the free base or free acid, without being biologically or otherwise undesirable. Salts are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like, 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 or organic base to the free acid. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium salts, and the like. Salts derived from organic bases include, but are not limited to, salts of 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, polyimine resins, and the like.

[0038] The compounds of formula (I) may contain several asymmetric centers and may exist as optically pure enantiomers, mixtures of enantiomers, e.g. racemates, optically pure diastereoisomers, mixtures of diastereoisomers, diastereomeric racemates or mixtures of diastereomeric racemates.

[0039] According to the Cahn-Ingold-Prelog rules, the asymmetric carbon atom may be of the "R" or "S" configuration.

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

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

[0042] The term "prophylaxis" as used herein includes preventing or delaying the appearance of clinical symptoms of a condition, disorder or condition that develops in a mammal, particularly in a human suffering from or susceptible to the condition, disorder or condition, but who has not yet experienced or exhibited clinical or asymptomatic symptoms of the condition, disorder or condition.

[0043] The term "neuroinflammation," as used herein, refers to acute and chronic inflammation of nervous tissue, which is a major tissue component of two parts of the nervous system: the brain and spinal cord of the central nervous system (CNS), and the branching 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") relates to damage to the brain resulting from an external mechanical force such as rapid acceleration or deceleration, impact, blast, or penetration by a projectile.

[0045] The term "neurodegenerative disease" refers to diseases associated with the progressive loss of neuronal structure or function, 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 mental disorder) relates to a behavioral or mental pattern that can cause distress or impaired functioning in life. Such characteristics may occur as persistent, relapsing, and remitting, or as a single episode. Examples of mental disorders include, but are not limited to, anxiety and depression.

[0047] The term "pain" relates 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 particular example of pain is neuropathic pain, which is caused by injury or disease affecting any part of the nervous system involved in bodily sensations (i.e., the somatosensory system). In one embodiment, the "pain" is neuropathic pain resulting from amputation or thoracotomy. In one embodiment, the "pain" is chemotherapy-induced neuropathy.

[0048] The term "neurotoxicity" relates to toxicity in the nervous system. It occurs when exposure to natural or man-made toxic substances (neurotoxins) alters the normal activity of the nervous system, causing damage to nervous tissue. Examples of neurotoxicity include, but are not limited to, exposure to substances used in chemotherapy, radiation treatment, drug therapy, drugs of abuse, and organ transplants, 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 diseases characterized by the presence of a neoplasm or tumor, resulting from the abnormal and uncontrolled growth of cells (such cells are "cancer cells"). As used herein, the term cancer expressly includes, but is not limited to, hepatocellular carcinoma, colon carcinoma, and ovarian cancer.

[0050] The term "mammal," as used herein, includes both humans and non-humans, including, but not limited to, humans, non-human primates, canines, felines, murines, bovines, equines, and porcines. In a particularly preferred embodiment, the term "mammal" refers to humans.

[0051] Compounds of the Invention In a first aspect, the present invention provides a compound of formula (I) [ka] (In the formula, 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 line indicates the point of attachment to the remainder of formula (I)) is a heteroaryl selected from C is C6 to 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- to 14-membered heterocyclyl, C6-C 14 aryl, and 5- to 14-membered heteroaryl; E is C3 to C 10selected from cycloalkyl and 3- to 14-membered heterocyclyl; L 1 is a covalent bond, -CR 12 R 13 -, -CH2O-, -OCH2-, -CH2NH-, -NHCH2-, -CH2OCH2-, -O-, -NH-, -CH2CH2-, -CH=CH-, [ka] selected from -SO2NH-, -NHSO2-, -SO2NHCH2-, -CH2NHSO2-, -SO2-, -CH2SO2-, -SO2CH2-, -(CH2)2SO2-, -SO2(CH2)2-, carbonyl, -NHC(O)- and -C(O)NH-; L 2 is selected from a covalent bond, —CH—, —CHNH—, —NHCH—, —NH—, —N(C1-C6 alkyl)-, and —SO—; L 3 is selected from a covalent bond and —CH—; R 1 is hydrogen, halogen, radical [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-C6 alkyl-S(O)2-, C1-C6 alkyl-SO2-, halo-C1-C6 alkylS(O)2-, (C1-C6 alkyl)2N-SO2-, and halo-C1-C6 alkyl-C(O)-; R 2 , R 3 , and R 4 are each independently selected from hydrogen, halogen, C1-C6 alkyl, halo-C1-C6 alkyl, and 3- to 14-membered heterocyclyl; R 5 and R 6are each independently hydrogen, halogen, cyano, hydroxy, amino, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, halo-C1-C6 alkoxy, C3-C 10 cycloalkyl, and 3- to 14-membered heterocyclyl, 10 cycloalkyl and 3- to 14-membered heterocyclyl are optionally substituted by 1, 2, or 3 substituents selected from C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, halogen, cyano, amino, and hydroxy; R 7 is 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 is selected from hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy and hydroxy; R 9 represents 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] is selected from R 10 and R11 are each independently selected from hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, and oxo; R 12 is hydrogen, carbamoyl, C1-C6 alkyl-NHC(O)- and halo-C6-C 14 aryl, R 13 is hydrogen, or R 12 and R 13 However, together with the carbon atoms to which they are attached, C3 to C 10 forming a cycloalkyl, R 14 represents 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] is selected from R 15 is selected from hydrogen, halogen, hydroxy, oxo, and C1-C6 alkyl; R 16 is selected from hydrogen and halogen; R 17 is selected from hydrogen, C1-C6 alkyl, and halo-C1-C6 alkyl or a pharmaceutically acceptable salt thereof.

[0052] In one embodiment, the present invention provides a compound of formula (I) as 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 line indicates the point of attachment to the remainder of formula (I)) is a heteroaryl selected from C is C6 to 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 is 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-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)-; R 2 , R 3 , and R 4 are each independently selected from hydrogen, halogen, C1-C6 alkyl, halo-C1-C6 alkyl, and 3- to 14-membered heterocyclyl; R 5 and R 6are each independently hydrogen, halogen, cyano, hydroxy, amino, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, halo-C1-C6 alkoxy, C3-C 10 cycloalkyl, and 3- to 14-membered heterocyclyl; C3~C 10 cycloalkyl and 3- to 14-membered heterocyclyl are optionally substituted by 1, 2, or 3 substituents selected from C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, halogen, cyano, amino, and hydroxy; R 7 is 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 is selected from hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy and hydroxy; 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-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; 10 Cycloalkyl, 3- to 14-membered heterocyclyl, and C6-C 14 the aryl is optionally substituted with 1, 2, or 3 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 are each independently selected from hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, and oxo; R 12 is hydrogen, carbamoyl, C1-C6 alkyl-NHC(O)- and halo-C6-C 14 aryl, R 13 is hydrogen, or R 12 and R 13 together with the carbon atoms to which they are attached, form C3-C 10 Forms a cycloalkyl.

[0053] In one embodiment, the present invention provides a compound of formula (I) as 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 to 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-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)-; R 2 is selected from hydrogen, halogen, C1-C6 alkyl, halo-C1-C6 alkyl, and 3- to 14-membered 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-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; 10 Cycloalkyl, 3- to 14-membered heterocyclyl and C6-C 14 the aryl is optionally substituted with one or two substituents selected from halo-C1-C6 alkyl, 3- to 14-membered 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 14aryl, R 13 is hydrogen, or R 12 and R 13 together with the carbon atoms to which they are attached, form C3-C 10 Forms a cycloalkyl.

[0054] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: A is C6~C 14 selected from aryl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl; C is C6 to C 14 Aryl, C3-C 10 cycloalkyl, and 5- to 14-membered heteroaryl; L 1 is a covalent bond, -CR 12 R 13 selected from -, -CH2O-, -O-, -SO2NH-, and -SO2-; R 1 teeth, [ka] and R 2 is selected from hydrogen and C1-C6 alkyl; R 3 , R 4 , R 12 , and R 13 are all hydrogen, R 9 C1-C6 alkyl, halo-C1-C6 alkyl, halo-C1-C6 alkoxy, SF5, C3-C 10 cycloalkyl, 3- to 14-membered heterocyclyl, and C1-C6 alkyl-SO2-; 10 cycloalkyl and 3- to 14-membered heterocyclyl are optionally substituted with 1 or 2 substituents selected from halo-C1-C6 alkyl and hydroxy; R 10is selected from hydrogen, halogen and C1-C6 alkoxy; R 11 is selected from hydrogen and halogen.

[0055] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt 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 selected from -, -CH2O-, -O-, -SO2NH-, and -SO2-; R 1 teeth, [ka] and R 2 is selected from hydrogen and methyl; R 3 , R 4 , R 12 , and R 13 are all hydrogen, R 9 is selected from tert-butyl, CF3, CF3O, SF5, cyclopropyl, azetidinyl, pyrrolidinyl and methylsulfonyl, wherein cyclopropyl, azetidinyl and pyrrolidinyl are optionally substituted with one or two substituents selected from CF3 and hydroxy; R 10 is selected from hydrogen, fluoro, chloro and methoxy; R 11 is selected from hydrogen and fluoro.

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

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

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

[0059] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: A is, [ka] is selected from C is C6 to 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- to 14-membered heterocyclyl, C6-C 14 aryl, and 5- to 14-membered heteroaryl; E is C3 to C 10 selected from cycloalkyl 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—; L 2 is selected from a covalent bond, —CH—, —CHNH—, —NHCH—, —NH—, —N(C1-C6 alkyl)-, and —SO—; L 3 is selected from a covalent bond and —CH—; R 1 teeth, [ka] Halo-C1~C6 alkoxy, C1~C6 alkyl-SO2NH-, C3~C 10 selected from 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)-; R 2 is selected from hydrogen, halogen, C1-C6 alkyl, halo-C1-C6 alkyl, and 3- to 14-membered heterocyclyl; R 3 is selected from hydrogen and halogen; R 4 is hydrogen, R 9represents 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 to C 10 Cycloalkyl, 3- to 14-membered heterocyclyl and C6-C 14 the aryl is optionally substituted with one or two substituents selected from halo-C1-C6 alkyl, 3- to 14-membered 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 14 aryl, R 13 is hydrogen, or R 12 and R 13 However, together with the carbon atoms to which they are attached, C3 to C 10 forming a cycloalkyl, R 14represents 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] is selected from R 15 is selected from hydrogen, halogen, hydroxy, oxo, and C1-C6 alkyl; R 16 is selected from hydrogen and halogen; R 17 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) as described herein, or a pharmaceutically acceptable salt thereof: A is, [ka] is selected from C is C6 to 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- to 14-membered heterocyclyl, C6-C 14 aryl, and 5- to 14-membered heteroaryl; E is C3 to C 10 selected from cycloalkyl 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—; L 2 is selected from a covalent bond, —CH—, —CHNH—, —NHCH—, —NH—, —N(C1-C6 alkyl)-, and —SO—; L 3 is selected from a covalent bond and —CH—; R 1 teeth, [ka] Halo-C1~C6 alkoxy, C1~C6 alkyl-SO2NH-, C3~C 10 selected from 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)-; R 2 is selected from hydrogen, halogen, C1-C6 alkyl, halo-C1-C6 alkyl, and 3- to 14-membered heterocyclyl; R 3 is selected from hydrogen and halogen; R 4 is hydrogen, R 9 represents 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 to C 10 Cycloalkyl, 3- to 14-membered heterocyclyl and C6-C 14 the aryl is optionally substituted with one or two substituents selected from halo-C1-C6 alkyl, 3- to 14-membered 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 14 aryl, R 13 is hydrogen, or R 12 and R 13 However, together with the carbon atoms to which they are attached, C3 to C 10 forming a cycloalkyl, R 14 represents 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] is selected from R 15 is selected from hydrogen, halogen, hydroxy, oxo, and C1-C6 alkyl; R 16 is selected from hydrogen and halogen; R 17is selected from hydrogen, C1-C6 alkyl, and halo-C1-C6 alkyl.

[0061] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: A is, [ka] is selected from C is C6 to C 14 Aryl, C3-C 10 cycloalkyl, and 5- to 14-membered heteroaryl; D is C3~C 10 selected from cycloalkyl and 3- to 14-membered heterocyclyl; L 1 is a covalent bond, -CR 12 R 13 selected from -, -CH2O-, -O-, -SO2NH-, and -SO2-; L 2 is selected from a covalent bond and —CH—; R 1 teeth, [ka] and R 2 is selected from hydrogen and C1-C6 alkyl; R 3 , R 4 , R 12 , and R 13 are all hydrogen, R 9 is halogen, C1-C6 alkyl, halo-C1-C6 alkyl, halo-C1-C6 alkoxy, SF5, C1-C6 alkyl-SO2-, [ka] [ka] and [ka] is selected from R 10 is selected from hydrogen, halogen, haloC1-C6 alkyl, and C1-C6 alkoxy; R 11 is selected from hydrogen and halogen; R 14 is selected from hydrogen and halo-C1-C6 alkyl; R 15 is selected from hydrogen and hydroxy; R 16 is hydrogen.

[0062] In one embodiment, the present invention provides a compound of formula (I) as 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 to 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- to 14-membered heterocyclyl, C6-C 14 aryl, and 5- to 14-membered heteroaryl; E is C3 to C 10 selected from cycloalkyl 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—; L 2 is selected from a covalent bond, —CH—, —CHNH—, —NHCH—, —NH—, —N(C1-C6 alkyl)-, and —SO—; L 3 is selected from a covalent bond and —CH—; R 1 teeth, [ka] Halo-C1~C6 alkoxy, C1~C6 alkyl-SO2NH-, C3~C 10 selected from 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)-; R 2 is selected from hydrogen, halogen, C1-C6 alkyl, halo-C1-C6 alkyl, and 3- to 14-membered heterocyclyl; R 3 is selected from hydrogen and halogen; R 4 is hydrogen, R 9 represents 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 to C 10 Cycloalkyl, 3- to 14-membered heterocyclyl and C6-C 14 the aryl is optionally substituted with one or two substituents selected from halo-C1-C6 alkyl, 3- to 14-membered 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 14 aryl, R 13 is hydrogen, or R 12 and R 13 together with the carbon atoms to which they are attached, form C3-C 10 forming a cycloalkyl, R 14 represents 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] is selected from R 15 is selected from hydrogen, halogen, hydroxy, oxo, and C1-C6 alkyl; R 16 is selected from hydrogen and halogen; R 17is selected from hydrogen, C1-C6 alkyl, and halo-C1-C6 alkyl.

[0063] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: A is C6~C 14 selected from aryl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl; C is C6 to C 14 Aryl, C3-C 10 cycloalkyl, and 5- to 14-membered heteroaryl; D is C3~C 10 selected from cycloalkyl and 3- to 14-membered heterocyclyl; L 1 is a covalent bond, -CR 12 R 13 selected from -, -CH2O-, -O-, -SO2NH-, and -SO2-; L 2 is selected from a covalent bond and —CH—; R 1 teeth, [ka] and R 2 is selected from hydrogen and C1-C6 alkyl; R 3 , R 4 , R 12 , and R 13 are all hydrogen, R 9 is halogen, C1-C6 alkyl, halo-C1-C6 alkyl, halo-C1-C6 alkoxy, SF5, C1-C6 alkyl-SO2-, [ka] [ka] and [ka] is selected from R 10 is selected from hydrogen, halogen, haloC1-C6 alkyl, and C1-C6 alkoxy; R 11 is selected from hydrogen and halogen; R 14 is selected from hydrogen and halo-C1-C6 alkyl; R 15 is selected from hydrogen and hydroxy; R 16 is hydrogen.

[0064] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt 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, azetidinyl and pyrrolidinyl; L 1 is a covalent bond, -CR 12 R 13 selected from -, -CH2O-, -O-, -SO2NH-, and -SO2-; L 2 is selected from a covalent bond and —CH—; R 1 teeth, [ka] and R 2 is selected from hydrogen and methyl; R 3 , R 4 , R 12 , and R13 are all hydrogen, R 9 are fluoro, chloro, tert-butyl, CF3, CF3O, SF5, methylsulfonyl, [ka] [ka] and [ka] is selected from R 10 is selected from hydrogen, fluoro, chloro, CF3, and methoxy; R 11 is selected from hydrogen and fluoro; R 14 is selected from hydrogen and CF3, R 15 is selected from hydrogen and hydroxy; R 16 is hydrogen.

[0065] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: B is B-1 to B-6: [ka] (The wavy line indicates the point of attachment to the remainder of formula (I)) is a heteroaryl selected from R 5 is hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, C3-C 10 cycloalkyl, and 3- to 14-membered heterocyclyl, 10 cycloalkyl is optionally substituted with one C1-C6 alkyl substituent; R6 is selected from hydrogen and halogen; R 7 is absent or is hydrogen.

[0066] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: B, [ka] (The wavy line indicates the point of attachment to the remainder of formula (I)) and R 5 is C1-C6 alkyl and C3-C 10 cycloalkyl; R 6 is hydrogen, R 7 does not exist.

[0067] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: B is [ka] (The wavy line indicates the point of attachment to the remainder of formula (I)) and R 5 is selected from ethyl and cyclopropyl; R 6 is hydrogen, R 7 does not exist.

[0068] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: B is B-1 to B-10: [ka] (The wavy line indicates the point of attachment to the remainder of formula (I)) is a heteroaryl selected from R 5 is hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, C3-C 10 cycloalkyl, and 3- to 14-membered heterocyclyl, 10 cycloalkyl is optionally substituted with one substituent selected from hydroxy and C1-C6 alkyl; R 6 is selected from hydrogen and halogen; R 7 is absent or is hydrogen.

[0069] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: B is [ka] (The wavy line indicates the point of attachment to the remainder of formula (I)) and R 5 is C1-C6 alkyl, halo-C1-C6 alkyl, and C3-C 10 cycloalkyl, and the C3 to C 10 The cycloalkyl is optionally substituted with one hydroxy substituent; R 6 is hydrogen, R 7 does not exist.

[0070] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: B is [ka] (The wavy line indicates the point of attachment to the remainder of formula (I)) and R 5 is selected from ethyl, CF3, and cyclopropyl, which cyclopropyl is optionally substituted with one hydroxy substituent; R 6 is hydrogen, R 7 does not exist.

[0071] In a preferred embodiment, the present invention provides R 8 is hydrogen or hydroxy; or a pharmaceutically acceptable salt thereof.

[0072] In a particularly preferred embodiment, the present invention provides 8 is hydrogen, or a pharmaceutically acceptable salt thereof.

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

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

[0075] In one embodiment, the present invention provides a compound of formula (I) as 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 line indicates the point of attachment to the remainder of formula (I)) is a heteroaryl selected from C is C6 to 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-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)-; R 2 is selected from hydrogen, halogen, C1-C6 alkyl, halo-C1-C6 alkyl, and 3- to 14-membered heterocyclyl; R 3 is selected from hydrogen and halogen; R 4 is hydrogen, R 5 is hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, C3-C 10 cycloalkyl, and 3- to 14-membered heterocyclyl,10 cycloalkyl is optionally substituted with one C1-C6 alkyl substituent; R 6 is selected from hydrogen and halogen; R 7 is absent or is hydrogen, R 8 is hydrogen or hydroxy, 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-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; 10 Cycloalkyl, 3- to 14-membered heterocyclyl and C6-C 14 the aryl is optionally substituted with one or two substituents selected from halo-C1-C6 alkyl, 3- to 14-membered 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 14 aryl, R 13 is hydrogen, or R 12 and R 13 together with the carbon atoms to which they are attached, form C3-C 10 Forms a cycloalkyl.

[0076] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: A is C6~C 14 selected from aryl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl; B is [ka] (The wavy line indicates the point of attachment to the remainder of formula (I)) and C is C6 to C 14 Aryl, C3-C 10 cycloalkyl, and 5- to 14-membered heteroaryl; L 1 is a covalent bond, -CR 12 R 13 selected from -, -CH2O-, -O-, -SO2NH-, and -SO2-; R 1 teeth, [ka] and R 2 is selected from hydrogen and C1-C6 alkyl; R 3 , R 4 , R 6 , R 8 , R 12 and R 13 are all hydrogen, R 5 is C1-C6 alkyl and C3-C 10 cycloalkyl; R 7 does not exist, R 9 C1-C6 alkyl, halo-C1-C6 alkyl, halo-C1-C6 alkoxy, SF5, C3-C 10 cycloalkyl, 3- to 14-membered heterocyclyl, and C1-C6 alkyl-SO2-; 10cycloalkyl and 3- to 14-membered heterocyclyl are optionally substituted with 1 or 2 substituents selected from halo-C1-C6 alkyl and hydroxy; R 10 is selected from hydrogen, halogen and C1-C6 alkoxy; R 11 is selected from hydrogen and halogen.

[0077] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt 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 line indicates the point of attachment to the remainder of formula (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 selected from -, -CH2O-, -O-, -SO2NH-, and -SO2-; R 1 teeth, [ka] and R 2 is selected from hydrogen and methyl; R 3 , R 4 , R 6 , R 8 , R 12 and R 13 are all hydrogen, R 5 is selected from ethyl and cyclopropyl; R 7 does not exist, R 9 is selected from tert-butyl, CF3, CF3O, SF5, cyclopropyl, azetidinyl, pyrrolidinyl and methylsulfonyl, wherein cyclopropyl, azetidinyl and pyrrolidinyl are optionally substituted with one or two substituents selected from CF3 and hydroxy; R 10 is selected from hydrogen, fluoro, chloro and methoxy; R 11 is selected from hydrogen and fluoro.

[0078] In one embodiment, the present invention provides a compound of formula (I) as 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 line indicates the point of attachment to the remainder of formula (I)) is a heteroaryl selected from C is C6 to 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- to 14-membered heterocyclyl, C6-C 14 aryl, and 5- to 14-membered heteroaryl; E is C3 to C 10 selected from cycloalkyl 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—; L 2 is selected from a covalent bond, —CH—, —CHNH—, —NHCH—, —NH—, —N(C1-C6 alkyl)-, and —SO—; L 3 is selected from a covalent bond and —CH—; R 1 teeth, [ka] Halo-C1~C6 alkoxy, C1~C6 alkyl-SO2NH-, C3~C 10 selected from 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)-; R 2 is selected from hydrogen, halogen, C1-C6 alkyl, halo-C1-C6 alkyl, and 3- to 14-membered heterocyclyl; R 3 is selected from hydrogen and halogen; R 4 is hydrogen, R 5 is hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, C3-C 10 cycloalkyl, and 3- to 14-membered heterocyclyl, 10 cycloalkyl is optionally substituted with one substituent selected from hydroxy and C1-C6 alkyl; R 6 is selected from hydrogen and halogen; R 7 is absent or is hydrogen, R 8 is hydrogen or hydroxy, R 9 represents 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] is selected from 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 14 aryl, R 13 is hydrogen, or R 12 and R 13 together with the carbon atoms to which they are attached, form C3-C 10 forming a cycloalkyl, R 14represents 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] is selected from R 15 is selected from hydrogen, halogen, hydroxy, oxo, and C1-C6 alkyl; R 16 is selected from hydrogen and halogen; R 17 is selected from hydrogen, C1-C6 alkyl, and halo-C1-C6 alkyl.

[0079] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: X is CR 8 and A is C6~C 14 selected from aryl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl; B is [ka] (The wavy line indicates the point of attachment to the remainder of formula (I)) and C is C6 to C 14 Aryl, C3-C 10 cycloalkyl, and 5- to 14-membered heteroaryl; D is C3~C 10 selected from cycloalkyl and 3- to 14-membered heterocyclyl; L 1 is a covalent bond, -CR 12 R 13 selected from -, -CH2O-, -O-, -SO2NH-, and -SO2-; L 2 is selected from a covalent bond and —CH—; R 1 teeth, [ka] and R 2 is selected from hydrogen and C1-C6 alkyl; R 3 , R 4 , R 6 , R 8 , R 12 and R 13 are all hydrogen, R 5 is C1-C6 alkyl, halo-C1-C6 alkyl, and C3-C 10 cycloalkyl, and the C3 to C 10 The cycloalkyl is optionally substituted with one hydroxy substituent; R 7 does not exist, R 9 is halogen, C1-C6 alkyl, halo-C1-C6 alkyl, halo-C1-C6 alkoxy, SF5, C1-C6 alkyl-SO2-, [ka] [ka] and [ka] is selected from R 10 is selected from hydrogen, halogen, haloC1-C6 alkyl, and C1-C6 alkoxy; R 11 is selected from hydrogen and halogen; R 14 is selected from hydrogen and halo-C1-C6 alkyl; R 15 is selected from hydrogen and hydroxy; R 16is hydrogen.

[0080] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt 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 line indicates the point of attachment to the remainder of formula (I)) and C is selected from phenyl, cyclopropyl, pyridyl, 1,2,4-oxadiazolyl, pyrazinyl, and pyrimidinyl; D is selected from cyclopropyl, azetidinyl and pyrrolidinyl; L 1 is a covalent bond, -CR 12 R 13 selected from -, -CH2O-, -O-, -SO2NH-, and -SO2-; L 2 is selected from a covalent bond and —CH—; R 1 teeth, [ka] and R 2 is selected from hydrogen and methyl; R 3 , R 4 , R 6 , R 8 , R 12 and R 13 are all hydrogen, R 5 is selected from ethyl, CF3, and cyclopropyl, which cyclopropyl is optionally substituted with one hydroxy substituent; R 7 does not exist, R 9 are fluoro, chloro, tert-butyl, CF3, CF3O, SF5, methylsulfonyl, [ka] [ka] and [ka] is selected from R 10 is selected from hydrogen, fluoro, chloro, CF3, and methoxy; R 11 is selected from hydrogen and fluoro; R 14 is selected from hydrogen and CF3, R 15 is selected from hydrogen and hydroxy; R 16 is hydrogen.

[0081] In one embodiment, the present invention provides a compound in which A is C6 to C 14 Aryl, C3-C 10 Provided herein are compounds of formula (I), or a pharmaceutically acceptable salt thereof, wherein the heteroaryl is selected from cycloalkyl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl.

[0082] In one embodiment, the present invention provides a method for producing a compound of the present invention, wherein B is B-1 to B-6: [ka] (The wavy line indicates the point of attachment to the remainder of formula (I)) or a pharmaceutically acceptable salt thereof.

[0083] In one embodiment, the present invention provides a method for producing a compound of the present invention, wherein B is B-1 to B-10: [ka] (The wavy line indicates the point of attachment to the remainder of formula (I)) or a pharmaceutically acceptable salt thereof.

[0084] In one embodiment, the present invention provides a compound in which C is C to C 14 Aryl, C3-C 10 Provided herein are compounds of formula (I), or a pharmaceutically acceptable salt thereof, wherein the heteroaryl is selected from cycloalkyl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl.

[0085] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt 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 a compound of formula (I) as described herein, or a pharmaceutically acceptable salt 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 provides a compound in which E is C3 to C 10 Provided are compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: R is selected from cycloalkyl and 3- to 14-membered heterocyclyl.

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

[0089] In one embodiment, the present invention provides a method for producing a compound comprising: 1 is a covalent bond, -CR 12 R 13 -, -CH2O-, -CH2NH-, -CH2OCH2-, -O-, -NH-, [ka] is selected from —SO2NH—, —NHSO2—, —SO2NHCH2—, —CH2NHSO2—, —SO2—, —CH2SO2—, —(CH2)2SO2—, carbonyl, and —C(O)NH—; R 12 and R 13

[0013] Provided herein are compounds of formula (I), or a pharmaceutically acceptable salt thereof, wherein:

[0090] In one embodiment, the present invention provides a method for producing a compound comprising: 2 is selected from a covalent bond, —CH—, —CHNH—, —NHCH—, —NH—, —N(C1-C6 alkyl)-, and —SO—, or a pharmaceutically acceptable salt thereof.

[0091] In one embodiment, the present invention provides a method for producing a compound comprising: 3 is selected from a covalent bond and —CH 2 —, or a pharmaceutically acceptable salt thereof.

[0092] In one embodiment, the present invention provides a compound comprising R 1 but, [ka] Halo-C1~C6 alkoxy, C1~C6 alkyl-SO2NH-, C3~C 10 is selected from 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)-; R 9 , R10 , R 11 , L 1 and C is as defined herein, or a pharmaceutically acceptable salt thereof.

[0093] In one embodiment, the present invention provides a compound comprising R 2 is selected from hydrogen, halogen, C1-C6 alkyl, halo-C1-C6 alkyl, and 3- to 14-membered heterocyclyl, or a pharmaceutically acceptable salt thereof.

[0094] In one embodiment, the present invention provides a compound comprising R 3 is selected from hydrogen and halogen, or a pharmaceutically acceptable salt thereof.

[0095] In a preferred embodiment, the present invention provides R 4 is hydrogen, or a pharmaceutically acceptable salt thereof.

[0096] In one embodiment, the present invention provides a compound comprising R 5 is hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, C3-C 10 cycloalkyl, and 3- to 14-membered heterocyclyl, 10 Provided are compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein cycloalkyl is optionally substituted with one C1-C6 alkyl substituent.

[0097] In one embodiment, the present invention provides a compound comprising R 5 is hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, C3-C 10 cycloalkyl, and 3- to 14-membered heterocyclyl, 10Provided herein are compounds of formula (I), or pharmaceutically acceptable salts thereof, wherein cycloalkyl is optionally substituted with one substituent selected from hydroxy and C1-C6 alkyl.

[0098] In one embodiment, the present invention provides a compound comprising R 6 is selected from hydrogen and halogen, or a pharmaceutically acceptable salt thereof.

[0099] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: 7 is absent or is hydrogen, or a pharmaceutically acceptable salt thereof.

[0100] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: 8 is hydrogen or hydroxy; or a pharmaceutically acceptable salt thereof.

[0101] In one embodiment, the present invention provides a compound comprising 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-membered heterocyclyl, C6-C 14 -aryl, C1-C6 alkyl-SO2-, amino, carboxy, carboxy-C1-C6 alkyl, C1-C6 alkoxycarbonylC1-C6 alkoxycarbonyl-C1-C6 alkyl-, NH2SO2-, carbamoyl, C1-C6 alkyl-C(O)NH-, halo-C1-C6 alkyl-NHC(O)- and oxo; 10 Cycloalkyl, 3- to 14-membered heterocyclyl and C6-C 14 Provided herein is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein aryl is optionally substituted with one or two substituents selected from halo-C1-C6 alkyl, 3- to 14-membered heterocyclyl, halogen, and hydroxy.

[0102] In one embodiment, the present invention provides a compound comprising R 9 is 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 provides a compound of formula (I) as described herein, or a pharmaceutically described compound thereof, or a pharmaceutically acceptable salt thereof, as defined herein.

[0103] In one embodiment, the present invention provides a compound comprising R 10 is selected from hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, and oxo, or a pharmaceutically acceptable salt thereof.

[0104] In one embodiment, the present invention provides a compound comprising R 11 is selected from hydrogen and halogen, or a pharmaceutically acceptable salt thereof.

[0105] In one embodiment, the present invention provides a compound comprising R 12 is hydrogen, carbamoyl, C1-C6 alkyl-NHC(O)-, and halo-C6-C 14 aryl, or a pharmaceutically acceptable salt thereof.

[0106] In a preferred embodiment, the present invention provides R 13 is hydrogen, or a pharmaceutically acceptable salt thereof.

[0107] In one embodiment, the present invention provides a compound comprising R 12 and R 13 However, together with the carbon atoms to which they are attached, C3 to C 10

[0023] Provided herein are compounds of formula (I), or pharmaceutically acceptable salts thereof, that form a cycloalkyl.

[0108] In a preferred embodiment, the present invention provides R 14 is 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 provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein:

[0109] In a preferred embodiment, the present invention provides R 15 is selected from hydrogen, halogen, hydroxy, oxo, and C1-C6 alkyl, or a pharmaceutically acceptable salt thereof.

[0110] In a preferred embodiment, the present invention provides R 16is selected from hydrogen and halogen, or a pharmaceutically acceptable salt thereof.

[0111] In a preferred embodiment, the present invention provides R 17 is selected from hydrogen, C1-C6 alkyl, and halo-C1-C6 alkyl, or a pharmaceutically acceptable salt thereof.

[0112] In a preferred embodiment, the present invention provides a method for treating a cycloaliphatic disorder in which A is C6 to C 14 Provided herein are compounds of formula (I), or a pharmaceutically acceptable salt thereof, wherein the heteroaryl is selected from aryl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl.

[0113] In a preferred embodiment, the present invention provides a compound in which B is [ka] (The wavy line indicates the point of attachment to the remainder of formula (I)) or a pharmaceutically acceptable salt thereof.

[0114] In a preferred embodiment, the present invention provides a cycloaliphatic alkylene compound in which C is C6 to C 14 Aryl, C3-C 10 Provided are compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein the aryl is selected from cycloalkyl, and 5- to 14-membered heteroaryl.

[0115] In a preferred embodiment, the present invention is a method for producing a hydroxyl group in which D is C3 to C 10 Provided are compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: R is selected from cycloalkyl and 3- to 14-membered heterocyclyl.

[0116] In a preferred embodiment, the present invention provides L 1 is a covalent bond, -CR 12 R 13-, -CH2O-, -O-, -SO2NH-, and -SO2-; R 12 and R 13

[0013] Provided are compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein:

[0117] In a preferred embodiment, the present invention provides L 2 is selected from a covalent bond and —CH 2 —, or a pharmaceutically acceptable salt thereof.

[0118] In a preferred embodiment, the present invention provides R 1 but [ka] and R 9 , R 10 , R 11 , L 1 and C is as defined herein, or a pharmaceutically acceptable salt thereof.

[0119] In a preferred embodiment, the present invention provides R 2 is selected from hydrogen and C1-C6 alkyl, or a pharmaceutically acceptable salt thereof.

[0120] In a preferred embodiment, the present invention provides R 3 is hydrogen, or a pharmaceutically acceptable salt thereof.

[0121] In a preferred embodiment, the present invention provides R 6 is hydrogen, or a pharmaceutically acceptable salt thereof.

[0122] In a preferred embodiment, the present invention provides R 8 is hydrogen, or a pharmaceutically acceptable salt thereof.

[0123] In a preferred embodiment, the present invention provides R 12 is hydrogen, or a pharmaceutically acceptable salt thereof.

[0124] In a preferred embodiment, the present invention provides R 5 is C1 to C6 alkyl and C3 to C 10

[0013] Provided are compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: R is 1 or 2; R is 2 or 3; R is 3 or 4; R is 4 or 5; R is 5 or 6; R is 6 or 7; R is 7 or 8; R is 8 or 9; R is 9 or 10; R is 10 or 11; R is 10 or 11;

[0125] In a preferred embodiment, the present invention provides R 5 is C1-C6 alkyl, halo-C1-C6 alkyl, and C3-C 10 cycloalkyl, and the C3 to C 10 Provided herein are compounds of formula (I), or pharmaceutically acceptable salts thereof, wherein the cycloalkyl is optionally substituted with one hydroxy substituent.

[0126] In a preferred embodiment, the present invention provides R 7 The present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein:

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

[0128] In a preferred embodiment, the present invention provides R 9is halogen, C1-C6 alkyl, halo-C1-C6 alkyl, halo-C1-C6 alkoxy, SF5, C1-C6 alkyl-SO2-, [ka] [ka] and [ka] or a pharmaceutically acceptable salt thereof.

[0129] In a preferred embodiment, the present invention provides R 10 is selected from hydrogen, halogen, and C1-C6 alkoxy, or a pharmaceutically acceptable salt thereof.

[0130] In a preferred embodiment, the present invention provides R 10 is selected from hydrogen, halogen, halo-C1-C6 alkoxy, and C1-C6 alkoxy, or a pharmaceutically acceptable salt thereof.

[0131] In a preferred embodiment, the present invention provides R 11 is selected from hydrogen and halogen, or a pharmaceutically acceptable salt thereof.

[0132] In a preferred embodiment, the present invention provides R 14 is selected from hydrogen and halo-C1-C6 alkyl, or a pharmaceutically acceptable salt thereof.

[0133] In a preferred embodiment, the present invention provides R 15is selected from hydrogen and hydroxy, or a pharmaceutically acceptable salt thereof.

[0134] In a preferred embodiment, the present invention provides R 16 is hydrogen, or a pharmaceutically acceptable salt thereof.

[0135] In a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt 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 a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein C is selected from phenyl, cyclopropyl, pyridyl, 1,2,4-oxadiazolyl, pyrazinyl and pyrimidinyl.

[0137] In a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt 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 provides 2 is selected from hydrogen and methyl, or a pharmaceutically acceptable salt thereof.

[0139] In a particularly preferred embodiment, the present invention provides 5 is selected from ethyl and cyclopropyl, or a pharmaceutically acceptable salt thereof.

[0140] In a particularly preferred embodiment, the present invention provides 5is selected from ethyl, CF3, and cyclopropyl, wherein said cyclopropyl is optionally substituted with one hydroxy substituent; or a pharmaceutically acceptable salt thereof.

[0141] In a particularly preferred embodiment, the present invention provides 7 The present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein

[0142] In a particularly preferred embodiment, the present invention comprises: 9 is selected from tert-butyl, CF, CF0, SF, cyclopropyl, azetidinyl, pyrrolidinyl and methylsulfonyl, and cyclopropyl, azetidinyl and pyrrolidinyl are optionally substituted with one or two substituents selected from CF and hydroxy, or a pharmaceutically acceptable salt thereof.

[0143] In a particularly preferred embodiment, the present invention provides 9 Fluoro, chloro, tert-butyl, CF3, CF3O, SF5, methylsulfonyl, [ka] [ka] and [ka] or a pharmaceutically acceptable salt thereof.

[0144] In a particularly preferred embodiment, the present invention provides 10 is selected from hydrogen, fluoro, chloro, and methoxy, or a pharmaceutically acceptable salt thereof.

[0145] In a particularly preferred embodiment, the present invention provides 10 is selected from hydrogen, fluoro, chloro, CF3, and methoxy, or a pharmaceutically acceptable salt thereof.

[0146] In a particularly preferred embodiment, the present invention provides 11 is selected from hydrogen and fluoro; or a pharmaceutically acceptable salt thereof.

[0147] In a particularly preferred embodiment, the present invention provides 14 is selected from hydrogen and CF3, or a pharmaceutically acceptable salt thereof.

[0148] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: A is C6~C 14 selected from aryl and 3- to 14-membered heterocyclyl; B is [ka] (The wavy line indicates the point of attachment to the remainder of formula (I)) and C is C6 to C 14 aryl and 5- to 14-membered heteroaryl; L 1 is a covalent bond 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 are hydrogen, R 5 is C3~C 10 is cycloalkyl, R 7 does not exist, R 9 is C1-C6 alkyl, halogen and C3-C 10 cycloalkyl, C3-C 10 cycloalkyl is optionally substituted with halo-C1-C6 alkyl; R 10 is selected from hydrogen and halogen.

[0149] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: A is selected from phenyl, azetidinyl, and 2-azaspiro[3.3]heptan-2-yl; B is [ka] (The wavy line indicates the point of attachment to the remainder of formula (I)) and C is selected from phenyl and 1,2,4-oxadiazolyl; L 1 is a covalent bond 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 are hydrogen, R 5is cyclopropyl, R 7 does not exist, R 9 is selected from tert-butyl, fluoro and cyclopropyl, wherein cyclopropyl is substituted with CF; R 10 is selected from hydrogen and fluoro.

[0150] In a preferred embodiment, the present invention provides a method for treating a cycloaliphatic disorder in which A is C6 to C 14 Provided are compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: R is selected from aryl and 3- to 14-membered heterocyclyl.

[0151] In a preferred embodiment, the present invention provides a cycloaliphatic alkylene compound in which C is C6 to C 14 Provided is a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: R is selected from aryl and 5- to 14-membered heteroaryl.

[0152] In a preferred embodiment, the present invention provides L 1 However, covalent bonds and -CR 12 R 13 or a pharmaceutically acceptable salt thereof.

[0153] In a preferred embodiment, the present invention provides R 2 is hydrogen, or a pharmaceutically acceptable salt thereof.

[0154] In a preferred embodiment, the present invention provides R 11 is hydrogen, or a pharmaceutically acceptable salt thereof.

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

[0156] In a preferred embodiment, the present invention provides R 9 is C1-C6 alkyl, halogen and C3-C 10 cycloalkyl, C3-C 10 Provided is a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein cycloalkyl is substituted with halo-C1-C6 alkyl.

[0157] In a preferred embodiment, the present invention provides R 10 is selected from hydrogen and halogen, or a pharmaceutically acceptable salt thereof.

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

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

[0160] In a particularly preferred embodiment, the present invention provides 5 is cyclopropyl; or a pharmaceutically acceptable salt thereof.

[0161] In a particularly preferred embodiment, the present invention provides 9 is selected from tert-butyl, fluoro and cyclopropyl, and cyclopropyl is substituted with CF3; or a pharmaceutically acceptable salt thereof.

[0162] In a particularly preferred embodiment, the present invention provides 10 is selected from hydrogen and fluoro; or a pharmaceutically acceptable salt thereof.

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

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

[0165] In a preferred embodiment, the present invention provides a cycloaliphatic alkylene compound in which C is C6 to C 14 Provided is a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: R is aryl.

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

[0167] In a particularly preferred embodiment, the present invention provides 1 is a covalent bond, or a pharmaceutically acceptable salt thereof.

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

[0169] In a particularly preferred embodiment, the present invention provides 9 is cyclopropyl substituted with CF3, or a pharmaceutically acceptable salt thereof.

[0170] In a particularly preferred embodiment, the present invention provides 10 is hydrogen, or a pharmaceutically acceptable salt thereof.

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

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

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

[0174] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt 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, pyridazinyl, benzofurazan-4-yl, tetrazolyl, isoxazolyl, pyrimidinyl, morpholinyl, 1,2-dihydropyridin, piperidyl, pyrrolidinyl, and thietanyl.

[0175] In one embodiment, the present invention provides a compound comprising R 1 but, [ka] 2,2,2-trifluoro-1,1-dimethyl-ethoxy, 2,2,2-trifluoroethoxy, C1-C6 alkyl-SO2NH-, C3-C 10 is selected from cycloalkyl-C1-C6 alkyl-S(O)2-, C1-C6 alkyl-SO2-, halo-C1-C6 alkyl-S(O)2-, (C1-C6 alkyl)2N-SO2-, halo-C1-C6 alkyl-C(O)-; R 9 , R 10 , R 11 , L 1 and C is as defined herein, or a pharmaceutically acceptable salt thereof.

[0176] In one embodiment, the present invention provides a compound comprising R 2 is selected from hydrogen, fluoro, methyl, CF3, and oxetanyl, or a pharmaceutically acceptable salt thereof.

[0177] In one embodiment, the present invention provides a compound comprising R 3 is selected from hydrogen and fluoro; or a pharmaceutically acceptable salt thereof.

[0178] In one embodiment, the present invention provides a compound comprising R5 is selected from hydrogen, fluoro, chloro, cyano, methyl, ethyl, methoxy, CF, cyclopropyl, cyclobutyl and azetidinyl, wherein said cyclopropyl and cyclobutyl are optionally substituted with one or more methyl substituents, or a pharmaceutically acceptable salt thereof.

[0179] In one embodiment, the present invention provides a compound comprising R 9 where: 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-trifluoropropan-2-yl)oxy), fluoro, cyano, SF5, cyclopropyl, cyclopropyl-CH2-, oxetanyl, azetidinyl, pyrrolidinyl, phenyl, methylsulfonyl, 2-neopentylsulfonyl, amino, carboxy, 2-methylpropanoic acid, 2,2-difluoropropanoic acid, Provided herein is a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, selected from methylpropanoate, methoxycarbonyl, methyl-2,2-dimethylpropanoate, methyl-2-methylpropanoate, NHSO-, carbamoyl, C-C alkyl-C(O)NH-, halo-C-C alkyl-NHC(O)- and oxo, wherein cyclopropyl, phenyl, oxetanyl, azetidinyl and pyrrolidinyl are optionally substituted with 1 to 2 substituents selected from CF, morpholinyl, halogen and hydroxy.

[0180] In one embodiment, the present invention provides 10 is selected from hydrogen, fluoro, chloro, cyano, methyl, methoxy, CF3, 2,2,2-trifluoroethyl, and oxo, or a pharmaceutically acceptable salt thereof.

[0181] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: X is CR 8 and A is a 3- to 14-membered heterocyclyl; B is [ka] (The wavy line indicates the point of attachment to the remainder of formula (I)) and C is C6 to C 14 is aryl, D is C3~C 10 is cycloalkyl, L 1 is a covalent bond, L 2 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 are all hydrogen, R 5 is C3~C 10 is cycloalkyl, R 7 does not exist, R 9 teeth, [ka] and R 14 is halo-C1-C6 alkyl.

[0182] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: X is CR 8 and A is azetidinyl; B is [ka] (The wavy line indicates the point of attachment to the remainder of formula (I)) and C is phenyl; D is cyclopropyl; L 1 is a covalent bond, L 2 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 are all hydrogen, R 5 is cyclopropyl, R 7 does not exist, R 9 teeth, [ka] and R 14 is CF3.

[0183] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: X is CR 8 and A is a 3- to 14-membered heterocyclyl; B is [ka] and C is a 5- to 14-membered heteroaryl; L 1 is -CH2-, R 1 ~R 8 is as defined herein.

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

[0185] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt 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 is -CH2-, R 1 ~R 8 is as defined herein.

[0186] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt 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 is -CH2-, R 5 is cyclopropyl, R 6 is hydrogen, R 7 does not exist, R 1 ~R 4 and R 8 is as defined herein.

[0187] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)azetidin-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(3-((1-(trifluoromethyl)cyclopropyl)methyl)-1,2,4-oxadiazol-5-yl)azetidin-1-yl)methanone; (4-(5-(tert-butyl)-1,2,4-oxadiazol-3-yl)phenyl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (4-(5-(tert-butyl)-1,2,4-oxadiazol-3-yl)phenyl)(6-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-[3-(trifluoromethyl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(4-chloropyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(4-cyclopropylpyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 1-[2-[4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)benzoyl]-2-azaspiro[3.3]heptan-6-yl]pyrazole-3-carbonitrile; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-[3-(1-methylcyclopropyl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-[5-(1-methylcyclopropyl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(4-methoxypyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(4,5,6,7-tetrahydroindazol-2-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(3-methoxypyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(6,7-dihydro-4H-pyrano[4,3-c]pyrazol-2-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(4-fluoropyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-[5-(trifluoromethyl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(5-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(6,7-dihydro-4H-pyrano[4,3-c]pyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(5-methoxypyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 1-[2-[4-(5-tert-butyl-1,2,4-oxadiazol-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-oxadiazol-3-yl)benzoyl]-2-azaspiro[3.3]heptan-6-yl]pyrazole-4-carbonitrile; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(4,5,6,7-tetrahydroindazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(6-methyl-3-pyridyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-methyl-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone; [6-(4-cyclopropylimidazol-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-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-methyl-5-[[1-(trifluoromethyl)cyclopropyl]methoxy]pyrazin-2-yl]methanone; [6-(4-cyclopropylimidazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-fluoro-6-[(1-methylcyclopropyl)methoxy]-3-pyridyl]methanone; [[6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-fluoro-6-[(1-methylcyclopropyl)methoxy]-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[[1-(trifluoromethyl)cyclopropyl]methoxy]pyrimidin-5-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(trifluoromethoxy)phenyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(1-morpholinocyclopropyl)phenyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(1,1-difluoroethyl)phenyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-fluoro-4-(trifluoromethoxy)phenyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(2,2,2-trifluoroethyl)phenyl]azetidin-1-yl]methanone; [3-(4-cyclopropyl-2-fluoro-phenyl)azetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 5-[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]-2-(trifluoromethoxy)benzonitrile; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-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-triazol-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)azetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(2-chloro-4-fluoro-phenoxy)-2-azaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]oxy]-5-(trifluoromethoxy)benzonitrile; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[2-fluoro-4-(pentafluoro-λ 6 -sulfanyl)phenyl]methoxy]azetidin-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((6-(trifluoromethyl)pyrazin-2-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]azetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[2-(trifluoromethyl)pyrimidin-4-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((6-(difluoromethoxy)pyridin-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[6-(trifluoromethyl)pyrimidin-4-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[4-(trifluoromethyl)pyrimidin-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((6-methoxypyridin-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((2-(trifluoromethyl)pyrimidin-5-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((5-fluoropyridin-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (4-(5-(tert-butyl)-1,2,4-oxadiazol-3-yl)phenyl)(6-(4-cyclopropyl-1H-imidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]oxy]-1-methyl-pyridin-2-one; [6-(5-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]azetidin-1-yl]-[6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[5-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-(trifluoromethoxy)benzyl)oxy)azetidin-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-(trifluoromethyl)benzyl)oxy)azetidin-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((2-fluoro-5-(trifluoromethyl)benzyl)oxy)azetidin-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((3-fluoro-4-(trifluoromethyl)benzyl)oxy)azetidin-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((2-fluoro-4-(trifluoromethoxy)benzyl)oxy)azetidin-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((3-fluoro-5-(trifluoromethyl)benzyl)oxy)azetidin-1-yl)methanone; (3-((2-chloro-4-fluorobenzyl)oxy)azetidin-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-fluoro-2-(trifluoromethyl)benzyl)oxy)azetidin-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((6-(trifluoromethyl)pyridin-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((5-(trifluoromethyl)pyridin-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-((5-chloropyridin-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-((6-chloropyridin-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [3-[2-chloro-4-(trifluoromethoxy)phenyl]azetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3,5-difluoro-4-(trifluoromethoxy)phenyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-fluoro-4-(trifluoromethoxy)phenyl]azetidin-1-yl]methanone; [3-(2-tert-butylthiazol-4-yl)azetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[4-[5-(2,2-dimethylpropyl)-1,2,4-oxadiazol-3-yl]phenyl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(3-cyclobutyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aR,6aS)-5-(2-chloro-4-fluoro-phenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-[4-(difluoromethoxy)phenyl]ethynyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aR,6aS)-5-(2-chloro-4-fluoro-phenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone; (3-(2-chloro-3-cyclopropylphenoxy)azetidin-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (3-(4-chloro-3-cyclopropylphenoxy)azetidin-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(2-fluoro-4-(trifluoromethyl)phenoxy)azetidin-1-yl)methanone; (3-(2-chloro-4-methylphenoxy)azetidin-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(2,4-dichlorophenoxy)azetidin-1-yl)methanone; (3-(4-chloro-2-fluorophenoxy)azetidin-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (3-((2-chloro-6-methylpyridin-3-yl)oxy)azetidin-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[3-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[4-(pentafluoro-λ 6 -sulfanyl)phenyl]methoxy]azetidin-1-yl]methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[2-fluoro-4-(pentafluoro-λ 6 -sulfanyl)phenyl]methoxy]azetidin-1-yl]methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[4-methyl-3-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-[2-(difluoromethyl)phenyl]ethynyl]azetidin-1-yl]methanone; [3-[(4-chloro-2-fluoro-phenyl)methoxy]azetidin-1-yl]-[6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[(2-chloro-4-fluoro-phenyl)methoxy]azetidin-1-yl]-[6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[(2,4-difluorophenyl)methoxy]azetidin-1-yl]methanone; 4-[[2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]oxy]-3-fluoro-benzonitrile; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-[4-(difluoromethoxy)-2-fluoro-phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; 2-[[rac-(3aS,6aR)-2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-yl]oxy]-5-(trifluoromethyl)benzonitrile; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; 5-[[rac-(3aS,6aR)-2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-yl]oxy]-2-(trifluoromethyl)benzonitrile; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-2-methoxy-phenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-2-methylsulfonyl-phenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-3-methyl-phenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-3-chloro-phenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone; 2-Fluoro-5-[[rac-(3aS,6aR)-2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-yl]oxy]benzonitrile; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4,5-difluoro-2-methyl-phenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone; 5-Fluoro-2-[[rac-(3aS,6aR)-2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-yl]oxy]benzonitrile; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-3-methylsulfonyl-phenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-3-methoxy-phenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[5-(trifluoromethyl)-3-pyridyl]methoxy]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-methyl-3-[[4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-[2-(difluoromethyl)phenyl]ethynyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-methyl-6-[(1-methylcyclopropyl)methoxy]-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-methyl-6-[(1-methylcyclopropyl)methoxy]-3-pyridyl]methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(2,2,2-trifluoroethoxy)pyrazol-1-yl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]azetidin-1-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(4-methylpyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(4-methylpyrazol-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-oxadiazol-3-yl)phenyl]-[6-(3-methylpyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[8-[[1-(trifluoromethyl)cyclopropyl]methoxy]-5-azaspiro[2.5]octan-5-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3,3-difluoro-4-[[1-(trifluoromethyl)cyclopropyl]methoxy]-1-piperidyl]methanone; [6-(3-cyclopropylpyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-methyl-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone; [6-(3-cyclopropylpyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-methyl-6-(2,2,2-trifluoro-1,1-dimethyl-ethoxy)-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-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-oxadiazol-3-yl)phenyl]-[6-(3-ethyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(4-ethylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-[4-(trifluoromethyl)imidazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(4-chloroimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 1-[2-[4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)benzoyl]-2-azaspiro[3.3]heptan-6-yl]imidazole-4-carbonitrile; [6-(3-cyclopropyl-1,2,4-triazol-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-oxadiazol-3-yl)-1-bicyclo[1.1.1]pentanyl]-[6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-1-bicyclo[1.1.1]pentanyl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[1-[1-(trifluoromethyl)cyclopropyl]triazol-4-yl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(2,2,2-trifluoroethoxy)pyrazol-1-yl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-5-yl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[1-[3-(trifluoromethyl)oxetan-3-yl]triazol-4-yl]azetidin-1-yl]methanone; [4-(5-tert-butyl-1,3,4-oxadiazol-2-yl)phenyl]-[6-(3-chloro-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,3,4-oxadiazol-2-yl)phenyl]-[6-(3-cyclopropylpyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(1-tert-butylpyrazol-4-yl)phenyl]-[6-(3-chloro-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(3-cyclopropylpyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(3-chloro-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[1-(trifluoromethyl)cyclopropyl]methoxymethyl]cyclobutyl]methanone; [6-(3-cyclopropylpyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-methyl-6-(2,2,2-trifluoro-1,1-dimethyl-ethoxy)-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-dimethyl-ethoxy)-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[1-(trifluoromethyl)cyclopropyl]methoxy]cyclobutyl]methanone; (6-(3-(azetidin-1-yl)-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-(trifluoromethyl)benzyl)oxy)azetidin-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-4-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(2-chloro-4-fluoro-phenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-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-oxadiazol-3-yl)phenyl]-[6-(5-cyclopropylpyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-(1-tert-butylpyrazol-4-yl)azetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-methyl-4-(trifluoromethoxy)phenyl]azetidin-1-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-cyclopropylphenoxy)azetidin-1-yl)methanone; [6-(3-cyclobutyl-1,2,4-triazol-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-cyclopropylpyridin-2-yl)oxy)azetidin-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(3-cyclopropyl-4-(trifluoromethyl)phenoxy)azetidin-1-yl)methanone; 5-cyclopropyl-2-((1-(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl)azetidin-3-yl)oxy)benzonitrile; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-cyclopropyl-2-fluorophenoxy)azetidin-1-yl)methanone; 2-Cyclopropyl-6-((1-(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl)azetidin-3-yl)oxy)benzonitrile; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; Methyl 3-[3-[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]oxyphenyl]-2,2-dimethylpropanoate; N-[2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]-3-(trifluoromethyl)benzenesulfonamide; [6-(3-cyclopropyl-1,2,4-triazol-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-oxadiazol-5-yl)-(4-fluorophenyl)methyl]-1-piperidyl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(3-cyclopropyl-2-fluorophenoxy)azetidin-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-(trifluoromethyl)phenoxy)azetidin-1-yl)methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(3-isopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-cyclopropyl-3-fluoropyridin-2-yl)oxy)azetidin-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]-3-pyridyl]azetidin-1-yl]methanone; (4-((3-cyclopropyl-1,2,4-oxadiazol-5-yl)(4-fluorophenyl)methyl)piperidin-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((6-cyclopropyl-2-fluoropyridin-3-yl)oxy)azetidin-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]azetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[3-hydroxy-3-(trifluoromethyl)pyrrolizino]-3-pyridyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(3R)-3-hydroxy-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidin-1-yl]methanone; N-[2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]-2,2-dimethyl-propane-1-sulfonamide; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(3S)-3-hydroxy-3-(trifluoromethyl)pyrrolizino]-3-pyridyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-methylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(2-methoxy-3-(trifluoromethyl)phenoxy)azetidin-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(3-cyclopropyl-4-fluorophenoxy)azetidin-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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)azetidin-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-oxadiazol-5-yl)-(4-fluorophenyl)methyl]-1-piperidyl]-[6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; 2-[[2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methyl]benzoic acid methyl ester; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-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-triazol-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-triazol-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-cyclopropylpyridin-3-yl)oxy)azetidin-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-(4-fluoro-2-mesyl-phenoxy)-2-azaspiro[3.5]nonan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzonitrile; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(2-fluoro-4-methylphenoxy)azetidin-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]methyl]-3-(trifluoromethyl)benzenesulfonamide; 6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-N-[[1-(trifluoromethyl)cyclopropyl]methyl]-2,6-diazaspiro[3.3]heptane-2-sulfonamide; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((6-(trifluoromethyl)pyridazin-3-yl)oxy)azetidin-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-((1,1,1-trifluoropropan-2-yl)oxy)-1H-pyrazol-1-yl)azetidin-1-yl)methanone; (2-Benzofurazan-4-ylsulfonyl-2,6-diazaspiro[3.3]heptan-6-yl)-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-[1-(2H-tetrazol-5-yl)cyclopropyl]phenyl]azetidin-1-yl]methanone; N-[[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-4-piperidyl]methyl]-4-(trifluoromethyl)benzenesulfonamide; (3-((6-chloro-5-cyclopropylpyridin-3-yl)oxy)azetidin-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-N-(4-fluorobenzyl)-2,6-diazaspiro[3.3]heptane-2-sulfonamide; 2-[[2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methyl]benzenesulfonamide; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-4-piperidyl]methyl]-4-(trifluoromethoxy)benzenesulfonamide; 6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-N-[1-(trifluoromethyl)cyclopropyl]-2,6-diazaspiro[3.3]heptane-2-sulfonamide; 4-(1-(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl)azetidin-3-yl)-1-(2,2,2-trifluoroethyl)pyridin-2(1H)-one; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[2-fluoro-4-(trifluoromethyl)benzyl]amino]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzoic acid methyl ester; (2-benzylsulfonyl-2,6-diazaspiro[3.3]heptan-6-yl)-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-(2-fluoro-4-mesyl-benzyl)oxyazetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[6-(trifluoromethyl)pyridazin-3-yl]amino]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-N-(1-methylcyclopropyl)-2,6-diazaspiro[3.3]heptane-2-sulfonamide; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((6-(trifluoromethyl)pyridin-3-yl)oxy)azetidin-1-yl)methanone; 4-chloro-N-[[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-4-piperidyl]methyl]benzenesulfonamide; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((2-cyclopropylpyrimidin-4-yl)oxy)azetidin-1-yl)methanone; (6-(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)(4-fluoro-2-(trifluoromethyl)phenyl)methanone; N-[[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]methyl]-4-(trifluoromethyl)benzenesulfonamide; N-[2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 2-[3-[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]oxyphenyl]-2-methylpropanoic acid; [3-(6-cyclopropylpyridazin-3-yl)oxyazetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(3,5-dimethylisoxazol-4-yl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((2-(trifluoromethyl)pyrimidin-4-yl)oxy)azetidin-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((6-(trifluoromethyl)pyrimidin-4-yl)oxy)azetidin-1-yl)methanone; [2-[(6-chloro-2-pyridyl)sulfonyl]-2,6-diazaspiro[3.3]heptan-6-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 3-[[6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzonitrile; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(5-(2,4-difluorophenyl)-4H-1,2,4-triazol-3-yl)azetidin-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(4-fluoro-2-methoxy-phenyl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; (2S)-2-[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; 4-[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]benzenesulfonamide; 3-[[6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]-4-fluoro-benzamide; N-[4-[[6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzamide; 3-[3-[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]oxyphenyl]-2,2-dimethylpropanoic acid; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(5-methylisoxazol-4-yl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; (2R)-2-[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-4-piperidyl]-2-(4-fluorophenyl)acetamide; N-[[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]methyl]-4-fluoro-2-(trifluoromethyl)benzenesulfonamide; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((6-(trifluoromethyl)pyrazin-2-yl)oxy)azetidin-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-(2-triflyl-2,6-diazaspiro[3.3]heptan-6-yl)methanone; 2-[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-4-piperidyl]-2-(4-fluorophenyl)acetamide; (2S)-2-[4-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]piperazino]-2-(4-fluorophenyl)acetamide; [3-[[4-(pentafluoro-l6-sulfanyl)phenyl]methoxy]azetidin-1-yl]-[6-[4-(trifluoromethyl)imidazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; 4-[[6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzonitrile; [6-(3-cyclopropyl-1,2,4-triazol-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-aminopyrimidin-5-yl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 2-[2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]-N-methyl-2-phenyl-acetamide; 1-(1-(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl)azetidin-3-yl)-N-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carboxamide; 2-[[2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methyl]benzoic acid; 6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-N,N-dimethyl-2,6-diazaspiro[3.3]heptane-2-sulfonamide; [6-(4-methylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[4-(pentafluoro-16-sulfanyl)phenyl]methoxy]azetidin-1-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)azetidin-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-4-piperidyl]methyl]-4-fluoro-benzenesulfonamide; [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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-4-piperidyl]-4-(trifluoromethyl)benzenesulfonamide; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(trifluoromethyl)pyridazin-3-yl]oxyazetidin-1-yl]methanone; 2-[[6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzamide; 4-[[6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzoic acid; N-[[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-4-piperidyl]methyl]benzenesulfonamide; (2R)-2-[4-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]piperazino]-2-(4-fluorophenyl)acetamide; 3-[[6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]-4-fluoro-benzoic acid; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(5-ethyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]piperazino]-2-(4-fluorophenyl)-N-methyl-acetamide; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(1-methylpyrazol-4-yl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; 2-[4-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-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)azetidin-1-yl)methanone; 2-[[6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]-N-methyl-benzamide; (2R)-2-[4-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]piperazino]-2-(4-fluorophenyl)-N-methyl-acetamide; N-[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-4-piperidyl]-4-fluoro-benzenesulfonamide; 1-[2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]-2,2,2-trifluoro-ethanone; 2-[[6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzoic acid; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]piperazino]-2-(4-fluorophenyl)-N-methyl-acetamide; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[6-(triazol-2-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[6-(triazol-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]azetidin-1-yl]-[6-[2-(trifluoromethyl)pyrimidin-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)triazol-4-yl]phenyl]azetidin-1-yl]-[6-(5-fluoro-3-pyridyl)-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[6-(5-fluoro-3-pyridyl)-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-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-triazol-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-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-(5-cyclopropyl-3-methyl-pyrazol-1-yl)-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-(5-cyclopropyl-3-methyl-pyrazol-1-yl)-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-(3,5-dimethylpyrazol-1-yl)-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(1H-pyrazolo[4,3-b]pyridin-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-triazol-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-triazol-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-triazol-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-triazol-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-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; 5-[[2-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]-2-(trifluoromethyl)benzonitrile; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; 4-[[2-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]-2-(trifluoromethyl)benzonitrile; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]-5-(trifluoromethyl)benzonitrile; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-3-pyridyl]azetidin-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(3R)-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidin-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[[6-(trifluoromethyl)-3-pyridyl]methyl]-1-bicyclo[1.1.1]pentanyl]azetidin-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]pyridin-5-ylmethyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[(5-cyclopropyl-4H-1,2,4-triazol-3-yl)methyl]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-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-methylsulfonyl-phenyl)-3-pyridyl]azetidin-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-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carbonyl]-2-azaspiro[3.4]octan-6-yl]oxy]-2-(trifluoromethyl)pyridine-4-carbonitrile; [6-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3.4]octan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-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-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[[2-methoxy-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[4-[5-[(1-methylcyclopropyl)methyl]-4H-1,2,4-triazol-3-yl]phenyl]azetidin-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[[1-(trifluoromethyl)cyclopropyl]methylamino]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(3S)-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidin-1-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[[4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidin-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptane-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-triazol-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-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-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-triazol-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-triazol-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-triazol-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-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(trifluoromethyl)pyrimidin-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-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]azetidin-1-yl]-[6-(1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[(4-dimethylphosphorylphenyl)methoxy]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[(4-dimethylphosphorylphenyl)methoxy]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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)triazol-4-yl]phenyl]azetidin-1-yl]-[6-(1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-[5-[1-(trifluoromethyl)cyclopropyl]-4H-1,2,4-triazol-3-yl]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[5-[1-(trifluoromethyl)cyclopropyl]-4H-1,2,4-triazol-3-yl]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]methanone; [3-[3-[[[1-(trifluoromethyl)cyclopropyl]amino]methyl]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-[[1-(trifluoromethyl)cyclopropyl]methylamino]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-[3-(trifluoromethyl)azetidin-1-yl]-3-pyridyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[2-[3-(trifluoromethyl)azetidin-1-yl]pyrimidin-5-yl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-3-pyridyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[4-[5-[(1-methylcyclopropyl)methyl]-4H-1,2,4-triazol-3-yl]phenyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-[(3S)-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-[(3R)-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-[(1,1-dioxothietan-3-yl)methylamino]-3-pyridyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; 2-[4-[1-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]phenyl]benzamide; [6-[[4-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-(5-cyclopropyl-4H-1,2,4-triazol-3-yl)-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]methanone; [3-[3-(5-cyclopropyl-4H-1,2,4-triazol-3-yl)-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]methanone; [3-[3-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2,7-diazaspiro[3.4]octan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[6-(trifluoromethyl)pyridazin-3-yl]methyl]-2,7-diazaspiro[3.4]octan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-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-triazol-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-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[[[1-(trifluoromethyl)cyclopropyl]amino]methyl]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[[1-(trifluoromethyl)cyclopropyl]methylamino]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-[5-[(1-methylcyclopropyl)methyl]-4H-1,2,4-triazol-3-yl]phenyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(5-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[[2-methoxy-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]-3-pyridyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-(3-hydroxy-3-methyl-azetidin-1-yl)-3-pyridyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; 3-(Trifluoromethyl)-N-[2-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-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-triazol-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-triazol-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-triazol-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-triazol-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-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-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-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[[3-(trifluoromethyl)oxetan-3-yl]amino]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-[5-[1-(trifluoromethyl)cyclopropyl]-4H-1,2,4-triazol-3-yl]phenyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(5-cyclopropyl-1H-1,2,4-triazol-3-yl)phenyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(3-fluoro-5-methylsulfonyl-phenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[5-[[1-(trifluoromethyl)cyclopropyl]methylamino]pyrazin-2-yl]azetidin-1-yl]methanone; [3-[4-(5-cyclobutyl-1H-1,2,4-triazol-3-yl)phenyl]azetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-fluoro-2-methylsulfonyl-phenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(3S)-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[[1-(trifluoromethyl)cyclopropyl]amino]-3-pyridyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[5-[[1-(trifluoromethyl)cyclopropyl]methylamino]-2-pyridyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-[3-(trifluoromethyl)azetidin-1-yl]pyrimidin-5-yl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(3S)-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-[(3S)-3-(trifluoromethyl)pyrrolidin-1-yl]pyrimidin-5-yl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-[(3R)-3-(trifluoromethyl)pyrrolidin-1-yl]pyrimidin-5-yl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(2-fluoro-4-methylsulfonyl-phenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-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-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[[1-(trifluoromethyl)cyclopropyl]amino]-3-pyridyl]azetidin-1-yl]methanone; (2R)-1-[4-[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]phenyl]-4,4-difluoro-piperidine-2-carboxamide; (2R)-1-[4-[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]phenyl]-4,4-difluoro-piperidine-2-carboxamide; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[3-(trifluoromethyl)azetidin-1-yl]-3-pyridyl]azetidin-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[3-(trifluoromethylsulfonyl)phenyl]methoxy]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]phenyl]-4,4-difluoro-piperidine-2-carboxamide; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-(3-hydroxy-3-methyl-azetidin-1-yl)-3-pyridyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(1,1-dioxothiolan-3-yl)amino]-3-pyridyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[4-(3-fluorophenoxy)-1-piperidyl]methanone; [3-(4-cyclobutylphenyl)azetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-(2-fluoro-6-methyl-phenyl)ethyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[(E)-2-(3-fluorophenyl)vinyl]azetidin-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]azetidin-1-yl]-[6-(5-fluoro-3-pyridyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[(2-chloro-4-fluoro-phenyl)methoxy]azetidin-1-yl]-[6-(5-fluoro-3-pyridyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[[2-chloro-4-(trifluoromethyl)phenyl]methylamino]azetidin-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]azetidin-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(trifluoromethyl)pyrazin-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]azetidin-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)azetidin-1-yl]-3-pyridyl]azetidin-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]azetidin-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-cyclopropyl-4-(trifluoromethyl)phenoxy]azetidin-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]azetidin-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-fluoro-phenyl)methoxy]azetidin-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-(4-isopropyl-N-methyl-anilino)-3-pyridyl]azetidin-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]heptane-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]benzonitrile; [3-[5-(2,4-dichlorophenyl)-2-pyridyl]azetidin-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-(2-chloro-4-methylsulfonyl-phenyl)-3-pyridyl]azetidin-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; and [3-[5-(4-chloro-2-fluoro-phenyl)-2-pyridyl]azetidin-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone is selected from.

[0188] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is (6-(3-cyclopropyl-1H-1,2,4-triazol-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-triazol-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-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)azetidin-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-cyclopropylphenoxy)azetidin-1-yl)methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(3-ethyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[2-fluoro-4-(pentafluoro-16-sulfanyl)phenyl]methoxy]azetidin-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((6-(trifluoromethyl)pyrazin-2-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-fluoro-4-(trifluoromethoxy)phenyl]azetidin-1-yl]methanone; N-[2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]-3-(trifluoromethyl)benzenesulfonamide; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((5-(trifluoromethyl)pyridin-2-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(3-fluoro-4-(trifluoromethoxy)phenyl)azetidin-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-(trifluoromethoxy)phenyl)azetidin-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-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-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]-3-pyridyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(3R)-3-hydroxy-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidin-1-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((2-(trifluoromethyl)pyrimidin-4-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(3S)-3-hydroxy-3-(trifluoromethyl)pyrrolizino]-3-pyridyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((5-(trifluoromethyl)pyrazin-2-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((3-fluoro-5-(trifluoromethyl)benzyl)oxy)azetidin-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((6-(trifluoromethyl)pyridin-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((6-(trifluoromethyl)pyrimidin-4-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-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-triazol-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-oxadiazol-3-yl)phenyl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-(4-fluoro-2-mesyl-phenoxy)-2-azaspiro[3.5]nonan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(5-methyl-6-((1-(trifluoromethyl)cyclopropyl)methoxy)pyridin-3-yl)methanone; and (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(3-((1-(trifluoromethyl)cyclopropyl)methyl)-1,2,4-oxadiazol-5-yl)azetidin-1-yl)methanone is selected from.

[0189] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)azetidin-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-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-oxadiazol-3-yl)phenyl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; and (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(3-((1-(trifluoromethyl)cyclopropyl)methyl)-1,2,4-oxadiazol-5-yl)azetidin-1-yl)methanone is selected from.

[0190] In certain embodiments, the present invention provides pharmaceutically acceptable salts of compounds according to formula (I) described herein. In more particular embodiments, the present invention provides compounds according to formula (I) described herein as the free base.

[0191] In some embodiments, compounds of formula (I) are isotopically labeled by having one or more atoms therein replaced by an atom having a different atomic mass or mass number. Such isotopically labeled (i.e., radiolabeled) compounds of formula (I) are considered to be within the scope of the present disclosure. Examples of isotopes that can be incorporated into compounds of formula (I) include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, and iodine, respectively, e.g., 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 Certain isotopically labeled compounds of formula (I), for example those incorporating a radioactive isotope, are useful in drug and / or substrate tissue distribution studies. The radioactive isotope tritium, i.e., 3 H and carbon-14, i.e., 14 C are particularly useful for this purpose given their ease of incorporation and ready means of detection. For example, compounds of formula (I) can be enriched with 1, 2, 5, 10, 25, 50, 75, 90, 95, or 99 percent of a given isotope.

[0192] Heavier isotopes, such as deuterium, i.e. 2 Substitutions such as H may result in greater metabolic stability and may confer certain therapeutic advantages, for example, by increasing in vivo half-life or requiring lower dosages.

[0193] 11 C. 18 F, 15 O and 13Substitution with positron emitting isotopes, such as N, can be useful in positron emission tomography (PET) studies for examining substrate receptor occupancy. Isotopically labeled compounds of formula (I) can generally be prepared by conventional techniques known to those skilled in the art, or by methods analogous to those described in the Examples set forth below, substituting an appropriate isotopically labeled reagent for the previously employed non-isotopically labeled reagent.

[0194] Manufacturing method The preparation of the compounds of formula (I) of the present invention can be carried out by sequential or convergent synthetic routes. The synthesis of the present invention is shown in the following general scheme. The skills required to carry out the reactions and purification of the resulting products are known to those skilled in the art. The substituents and indices used in the following process descriptions have the meanings given herein unless indicated to the contrary.

[0195] If one of the starting materials, intermediates or compounds of formula (I) contains one or more functional groups that are not stable or reactive under the reaction conditions of one or more reaction steps, suitable protecting groups (such as those described in "Protective Groups in Organic Chemistry", T.W. Greene and P.G.M. Hutts, 5th Edition, 2014, John Wiley & Sons, NY) can be introduced prior to a critical step by applying methods well known in the art. Such protecting groups can be removed at a later stage of the synthesis using standard methods described in the literature.

[0196] When the starting material or intermediate contains a stereocenter, the compound of formula (I) may 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. Racemates can be separated into their antipodes via diastereomeric salts, for example, by crystallization with an optically pure acid, or by separating the antipodes by specific chromatographic methods using either a chiral adsorbent or a chiral eluent. Starting materials and intermediates containing a stereocenter can also be separated to obtain diastereomerically / enantiomerically enriched starting materials and intermediates. The use of such diastereomerically / enantiomerically enriched starting materials and intermediates in the synthesis of the compound of formula (I) generally results in the respective diastereomerically / enantiomerically enriched compound of formula (I).

[0197] Those skilled in the art will recognize that in the synthesis of compounds of formula (I), unless otherwise desired, an "orthogonal protecting group strategy" can be applied to cleave some 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 has been described in the literature (e.g., Barany and R.B. Merrifield, 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 reaction sequence may vary depending on the reactivity and nature of the intermediates.

[0199] More specifically, compounds of formula (I) can be prepared by the methods described below, the methods described in the Examples, or similar methods. Suitable reaction conditions for the individual reaction steps are known to those skilled in the art. For literature-described reaction conditions affecting the described reactions, see, for example, Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 2nd Edition, Richard C. Larock, John Wiley & Sons, New York, NY, 1999. The reactions could be easily carried out with or without a solvent. There are no particular restrictions on the nature of the solvent used, so long as it does not adversely affect the reaction or the reagents involved and is capable of dissolving the reagents to at least some extent. The described reactions can occur over a wide range of temperatures, and the exact reaction temperature is not critical to the present invention. It is convenient to carry out the described reactions at temperatures ranging from -78°C to reflux. The reaction time required for the reaction can also vary widely, depending on many factors, particularly the reaction temperature and the nature of the reagents. However, a period of 0.5 hours to several days is usually sufficient to obtain the intermediates and compounds described. The reaction order is not limited to the order shown in the scheme, but the order of the reaction steps can be freely changed depending on the starting materials and their respective reactivities.

[0200] If the starting materials or intermediates are not commercially available or their synthesis is not described in the literature, they can be prepared analogously to existing procedures for similar analogs or as outlined in the experimental section.

[0201] The following abbreviations are used herein: AcOH = acetic acid, ACN = acetonitrile, Bn = benzyl, BINAP = (2,2'-bis(diphenylphosphino)-1,1'-binaphthyl), Boc = tert-butyloxycarbonyl, CAS RN = Chemical Abstracts Registry 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 = (diethylamino)sulfur trifluoride, DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene, DEAD = diethyl azodicarboxylate, DIAD = diisopropyl azodicarboxylate, DIBAL-H = diisobutylaluminum hydride, DMAP = 4-dimethylaminopyridine, DME = dimethoxyethane, DMEDA = N,N '-Dimethylethylenediamine, DMF = N,N-dimethylformamide, DIPEA = N,N-diisopropylethylamine, dppf = 1,1-bis(diphenylphosphino)ferrocene, EDC.HCl = N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride, EI = electron impact, ESI = electrospray ionization, EtOAc = 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-oxide hexafluorophosphate, HBTU = O-benzotriazole-N,N,N'N'-Tetramethyl-uronium-hexafluoro-phosphate, HCl = hydrogen chloride, HOBt = 1-hydroxy-1H-benzotriazole, HPLC = high performance liquid chromatography, iPrMgCl = isopropyl magnesium 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 cyanoborohydride, 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 = propylphosphonic anhydride, PE = petroleum ether, PG = protecting group, Pd-C = palladium-activated carbon, PdCl2(dppf)-CH2Cl2 = 1,1'-bis(diphenylphosphino)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 = reversed phase, RT = room temperature, SFC = supercritical fluid chromatography, S-PHOS = 2-dicyclohexylphosphino-2',6'-Dimethoxybiphenyl, TBAI = tetrabutylammonium iodide, TEA = triethylamine, TFA = trifluoroacetic acid, THF = tetrahydrofuran, TMEDA = N,N,N',N'-tetramethylethylenediamine, TS-TPP = triphenylphosphine-polymer-bound, ZnCl2 = zinc chloride, Hal = halogen, prep-TLC = preparative thin-layer chromatography.

[0202] Compounds of the invention of formula I, where 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 CHCN in the presence of a base such as DIPEA. In some cases, an alternative activated intermediate bearing a 4-nitrophenyl group instead of 1,2,4-triazole was used (Scheme 1). [ka]

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

[0204] Ring B is an N-linked aromatic heterocycle and X=CR 8In this case, the amine 3 can be generated by reacting the nucleophilic heteroaryl 5 with an 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, CsCO), 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 generated from the hydroxyl analog by reaction with MsCl in the presence of a mild base such as EtN. [ka]

[0205] Alternatively, compounds of formula I in which ring A is an N-linked aliphatic heterocycle can be generated 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 also corresponding to formula I (e.g., 14, 16) can be prepared in this manner. [ka]

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

[0207] Or, X is CR 8Compounds of Formula I, wherein ring B is an N-linked heteroaromatic ring, can be generated by reacting nucleophilic heteroaryl 5 with an appropriately functionalized intermediate 7 (Y=leaving group, e.g., OMs) in the presence of a base (e.g., CsCO, NaOtBu) (Scheme 6). Intermediate 7 can be generated by coupling an appropriate hydroxylated building block with ring A described in Schemes 1 or 4 to generate intermediate 8, followed by conversion of the hydroxyl group to a suitable leaving group (e.g., by mesylation in the presence of MsCl and base). Alternatively, hydroxylated intermediate 8 can be directly converted to compounds of Formula I using Mitsunobu-type conditions (e.g., PS-PPh, DIAD in THF) and nucleophilic heteroaryl 5. [ka]

[0208] Or, X=CR 8 When ring B is a C-linked (hetero)aryl, compounds of formula I can be generated using a metal-catalyzed cross-coupling reaction from appropriately functionalized intermediates 7 and 9, where one partner has an organometallic (e.g., zincate, boronate) typically generated 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 aryl halide 9 (Y = I) 2 =Br, I). Iodides 7 can be generated from the related hydroxy building blocks 8 by reaction with I2 and PPh3. [ka]

[0209] Alternatively, compounds of formula I with A = (substituted) pyridyl, (substituted) pyrimidinyl, or (substituted) pyridazinyl with a (halo)alkoxy R group were prepared by reacting compounds 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 generated from the corresponding alcohol by a Mitsunobu reaction (e.g., using cyanomethyltributylphosphorane). [ka]

[0210] Alternatively, compounds of Formula I with A = aliphatic (hetero)cycle and C = (hetero)aryl can be generated by nickel- or palladium-catalyzed coupling of boronic acid derivatives 11 (Y = B(OR)2) with iodides 12. Alternatively, bromides 11 (Y = Br) can be directly coupled 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, compounds of formula I having A=aliphatic (hetero)cycle and L1=oxygen (or containing it) can be prepared by the S reaction using a base such as NaH. N In a two-step reaction, alcohols of formula 13 (or other simple alcohol or haloalcohol groups) can be prepared by reacting them with an appropriately functionalized building block 14, where Y is a leaving group such as OM or I (Scheme 10). If desired, building block 14 can be generated from the corresponding alcohol (Y=OH, 16). [ka]

[0212] Alternatively, compounds of formula I in which L1 is (or contains) oxygen and C is (substituted) aliphatic (hetero)cyclic or (hetero)aryl (Y is S N 15 (Y is a leaving group such as OMs, Cl) can be prepared by reacting 15 with alcohol 16 in the presence of a base such as NaH (Scheme 11). [ka]

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

[0214] Alternatively, the building block of formula 18 (X) where 1 is (or contains) oxygen and C is an aliphatic (hetero)cycle, a small (halo)alkyl fragment or a (hetero)aryl. 1 is S N Ar substitution) can be reacted with 15 (X 1where PG is a leaving group such as OMs, Cl) with an appropriately protected alcohol building block 19, followed by deprotection under standard conditions (e.g., with TFA when PG=Boc) (Scheme 13). Alternatively, building blocks of formula 18 where L1=oxygen and C=(hetero)aryl can be prepared by the reaction of alcohol 19 with aryl (hetero)halides 15 (X 1 = typically Br, I) followed by deprotection. [ka]

[0215] Building blocks of formula 21 with A=(substituted)pyridyl, (substituted)pyrimidinyl or (substituted)pyridazinyl with a (halo)alkoxy R group can be prepared by reacting the building blocks of formula 20 (X 1 Heteroaryl compounds can be prepared by reacting an appropriately protected (e.g., as a methyl ester) heteroaryl acid (R = F, Cl) with the corresponding alcohol and a suitable base such as NaH or KOtBu. If further substitution on the heteroaryl R2 is required, this can typically be achieved via commercially available halides (R = Br, I) followed by metal-catalyzed cross-coupling (e.g., Suzuki, Negishi, Ir-catalyzed photochemistry). Protecting groups (if used) can be removed under standard conditions (e.g., alkaline hydrolysis of the methyl ester) (Scheme 14). Alternatively, these building blocks can be generated by synthesizing the appropriate bromo- or iodo-heteroarenes using standard techniques, followed by the introduction of the acid (or ester) functionality via a Pd-catalyzed carbonylation reaction. [ka]

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

[0217] The building blocks of formula 24 with A = aliphatic (hetero)cycle and C = (hetero)aryl can be prepared by the addition of appropriately protected boronic acid derivatives 11 (X 1 ═B(OR)2) can be generated by nickel or palladium catalyzed coupling with iodide 23. Alternatively, bromide 11 (X 1 =Br) can be directly coupled to 23 in a photochemical reaction using Ir[dF(CF3)ppy]2(dtbbpy)PF6, NiCl2·DME, dtbbpy, and (TMS)3SiH (Scheme 16). [ka]

[0218] The building blocks of formula 27 where C=(hetero)aryl are suitable for Suzuki reactions (e.g., (hetero)aryl halides (X 1=Br, I, Cl) can be generated by (Pd(dppf)Cl, KCO, dioxane / HO) followed by hydrogenation (e.g., Pd / C, H). The requisite boronate intermediate 25 can be generated by reacting the ketone with 4,4,5,5-tetramethyl-2-[(tetramethyl-1,3,2-dioxaborolan-2-yl)methyl]-1,3,2-dioxaborolane (LiTMP, THF, −78° C.) (Scheme 17). Alternatively, alkene 26 can be generated by a Wittig reaction using the ketone and the appropriate triphenylphosphonium bromide (generated from a benzyl bromide or heteroaryl equivalent) of ring C. Alternatively, building block 27 can be generated by generating a tosylhydrazone intermediate from an aldehyde on ring A (e.g., by condensation with 4-methylbenzenesulfonhydrazide) followed by reaction with the relevant (hetero)arylboronic acid (e.g., KCO, Bartlegger conditions) prior to deprotection. L1 = CR 12 R 13 and R 12 = carbamoyl, R 13 = hydrogen building blocks can be synthesized using standard techniques by a similar strategy involving condensation of a (hetero)arylacetonitrile with a ketone (52), followed by hydrogenation of the alkene intermediate generated by nitrile hydrolysis and amide formation. [ka]

[0219] The building blocks of formula 30, where L1 is oxygen and C is a phenol or (hetero)arylhydroxy (28), react with a nucleophilic (hetero)arylhydroxy anion (generated with a base, e.g., NaH) to form a nucleophilic (hetero)arylhydroxy anion, e.g., S N 2. Leaving group X at a suitable position for substitution 1The building block 30 can be prepared by reacting a suitably protected building block 29 with PG (OM, which can be generated from the hydroxy derivative using, for example, MsCl, Et3N). This can be followed by deprotection under standard conditions (e.g., with TFA when PG = Boc) (Scheme 18). Alternatively, the building block 30 can be prepared by the reaction of a phenol with an alcohol 29 (X 1 =OH) (using, for example, DIAD, PPh3, or 2-(tributyl-15-phosphanylidene)acetonitrile), followed by deprotection. [ka]

[0220] Alternatively, the building block of formula 32 with A=aliphatic (hetero)cycle and C=(hetero)aryl can be prepared by the boronic acid derivative 11 (X 1 Alternatively, bromides 11 (X = B(OR)2) can be generated by nickel or palladium catalyzed coupling with appropriately protected halides (Y = I or Br)31. 1 31 (Y = I or Br) can be directly coupled to 32 (Y = I or Br) via photochemistry using Ir[dF(CF3)ppy]2(dtbbpy)PF6, NiCl2.DME, dtbbpy, and (TMS)3SiH. Coupling is followed by an appropriate deprotection step (e.g., TsOH, for PG = Boc) (Scheme 19). [ka]

[0221] Alternatively, the building block of formula 35 with A = aliphatic (hetero)cycle, L = -OCH2- and C = (hetero)aryl can be prepared by adding a leaving group (e.g., X 1PG = Boc) with alcohol 34 in the presence of a base (e.g., NaH). Coupling is followed by a suitable deprotection step (e.g., TsOH or TFA when PG = Boc) (Scheme 20). This route is also suitable when C = a small aliphatic (hetero)cycle (e.g., cyclopropyl), or when ring C is replaced with a small alkyl or haloalkyl fragment. [ka]

[0222] Alternatively, the building blocks of formula 37 bearing an L═C═C triple bond can be converted to (hetero)aryl halides 11 (X) via Sonogashira coupling (e.g., Pd(PPh)Cl, CuI, TEA). 1 =Br or I) and an appropriately protected alkyne 36, followed by an appropriate deprotection step (e.g., TsOH or TFA when PG = Boc) (Scheme 21). [ka]

[0223] B=C-linked (hetero)aryl and X=CR 8 The building blocks of formula 38 can be generated by nickel- or palladium-catalyzed coupling of appropriately protected boronic acid derivatives 39 (Y = B(OR)2) with iodides or bromides (Z = I or Br) 40. Alternatively, bromides 39 (Y = Br) can be directly coupled with 40 (Z = I or Br) via photochemical reaction using Ir[dF(CF3)ppy]2(dtbbpy)PF6, NiCl2·DME, and dtbbpy-containing (TMS)3SiH (Scheme 22). Alternatively, cross-coupling can be performed under Negishi conditions using a zincate transiently generated from 39 (Y = I) and (hetero)halides 40 (Z = I, Br). [ka]

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

[0225] Alternatively, building blocks of formula 44 with L = -SO2NH- can be prepared from sulfonyl chloride 45, followed by the appropriate protected (spiro)cyclic amine (46) in the presence of a base such as DIPEA, followed by deprotection under standard conditions (e.g., with TsOH when PG = Boc) (Scheme 24). This sequence is also suitable when a small alkyl group is present in place of the C ring. [ka]

[0226] Alternatively, the building block of formula 47 (X 1 is S N Ar substitution is suitable for 48 (X 1 is a leaving group such as Cl or Br, and S N Ar (often adjacent to an aromatic N for reaction) can be prepared by reaction with an appropriately protected amine building block 49 in the presence of a base such as DIPEA, followed by deprotection under standard conditions (e.g., with TsOH when PG=Boc) (Scheme 25). [ka]

[0227] Alternatively, building blocks of formula 50 with L1 = NH2 or CH2NH can be installed by reductive amination reaction of amine 51 with an appropriately 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., with TsOH when PG = Boc) (Scheme 26). [ka]

[0228] Alternatively, building blocks of formula 53 where L1 = CH2 and A is N-linked can be prepared by reductive amination of aldehyde 54 with a suitably 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., with TsOH when PG = Boc) (Scheme 27). The same sequence can also be carried out to generate building blocks of formula 56, where L1 = CH2NH from aldehyde 54 and amine 57 (Scheme 28). [ka] [ka]

[0229] Alternatively, building blocks of formula 58 where L1 = SO2 and A is N-linked can be prepared from sulfonyl chloride 45 and an appropriately protected heterocycle A (55) in the presence of a base such as DIPEA, followed by deprotection under standard conditions (e.g., with TsOH when PG = Boc) (Scheme 29). This sequence is also appropriate when A is N-linked and R1 is C1-C6 alkyl-SO2-. [ka]

[0230] Alternatively, the building block of formula 59 where L1 = CH2 and A is N-linked can be prepared by the addition of a (hetero)arylmethyl halide (X2CO3) in a solvent such as ACN in the presence of a base such as K2CO3. 1 =Br,I) 60 can be prepared by reductive amination of a suitably protected heterocycle A (55), followed by deprotection under standard conditions (e.g., with TsOH when PG = Boc) (Scheme 30). [ka]

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

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

[0233] Or, L 1Sulfonylurea building blocks of formula 65 bearing = -NHSO2- or -CH2NHSO2- can be prepared by activation of 2-methyl-1-(2-methylimidazol-1-yl)sulfonyl-imidazole by methylation with methyl trifluoromethanesulfonate, followed by reaction with an appropriately protected amine 55, a further activation sequence by methylation with methyl trifluoromethanesulfonate followed by reaction with amine 51, and finally deprotection under standard conditions (e.g., with TsOH or TFA when PG = Boc) (Scheme 33). Alternatively, sulfonylurea building block 65 can be generated from sulfuryl chloride, followed by the sequential addition of 55 and 51 in the presence of a base such as Et3N or DIPEA, followed by final deprotection under standard conditions. [ka]

[0234] L1=bond and C=C bond (hetero)aryl and R 9 Building blocks bearing an amine (L = -NH- or -CHNH- and D is an aliphatic heterocycle such as cyclopropyl (66) or a C=N-bonded heterocycle (67)) can be prepared by the synthesis of intermediate 70 (X) using the relevant amine building blocks 71 or 72 (typically Pd-catalyzed, Buchwald reaction). 1 The required intermediate 70 can be generated by metal-catalyzed amination of a suitable N-substituted aryl group (Y = Br, Cl adjacent to an aromatic N). The required intermediate 70 can be obtained by the reaction of a suitably protected building block 69 (Y = I) with a zincate salt temporarily generated from the appropriate dihalogenated (hetero)aryl building block 68 (X = I). 2 is X 1 must be more reactive to cross-coupling conditions than X 2 = I or Br, and X 1 Alternatively, intermediate 70 can be prepared by a cross-coupling reaction such as the Negishi reaction between 69 (Y=N-NH-Ts) and boronic acid 68 (X = Br) (Scheme 34). 2=B(OH)2) in the presence of a base such as K2CO3. [ka]

[0235] Alternatively, amine 71 or 72 can be reacted with S N Ar reaction affords (hetero)aryl building block 68(X 1 =F) to generate intermediates 73 or 74, followed by cross-coupling with the A ring (typically using Ir[dF(CF3)ppy]2(dtbbpy)PF6, NiCl2, DME, dtbbpy, and (TMS)3SiH, followed by photochemistry of 69 (Y = Br) with halide 73 or 74) followed by deprotection (Scheme 35). Alternatively, R 9 This S produces an amine N The Ar approach is 70 (wherein X 1 (Scheme 34) Optionally, the copper catalyst S N Ar or Ullmann-type reactions were used in the reaction of 68 and 72 to give 74. [ka]

[0236] The building block with L1 = bond and C=C bonded (hetero)aryl and D=N bonded heteroaryl (57) was boronic acid 68 (X 1 =B(OH)2,X 2Intermediate 77 can be generated by Chan-Lam coupling (in the presence of Cu(OAc)) of Ir[dF(CF)ppy](dtbbpy)PF, NiCl, DME, dtbbpy, and (TMS)SiH) with a suitably protected (spiro)cyclic amine 69 (Y=Br) followed by deprotection (Scheme 36). Alternatively, in the case of C-linked heterocycles, heterocycle C can be constructed by standard heterocycle synthesis techniques prior to photochemical cross-coupling and deprotection. [ka]

[0237] Alternatively, building blocks of formula 78, with L and L bonds and where C and D are (hetero)aryl, can be prepared by reacting appropriately protected (spiro)cyclic amines (Y = I or Br) in two sequential cross-coupling reactions, followed by deprotection. Most typically, this involves Ni-catalyzed cross-coupling between 69 (Y = I) and building block 79, which has both bromide and boronic acid functionalities, to give bromo(hetero)aryl intermediate 80. Intermediate 80 could be coupled with boronic acid derivative 81 under Suzuki conditions, followed by deprotection, to give 78 (Scheme 37). [ka]

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

[0239] Building blocks of formula 85, where L1 = bond and L2 = -NHCH2-, can be generated by Curtius rearrangement of an appropriately 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 give amine 87, followed by further reductive amination of amine 87 with an appropriate aldehyde 88, followed by subsequent deprotection (Scheme 39). Alternatively, amine 87 can be used in heterocycle synthesis reactions (e.g., condensation with an appropriate 1,3-dione, O-(4-nitrobenzoyl)hydroxylamine to generate a pyrazole) to generate an N-linked heterocyclic D-ring. [ka]

[0240] The building block of formula 89, where L1 = bond and L2 = bond and C = heteroaryl, can be converted to a building block 90 ( 1 These compounds can be prepared using standard heteroaryl synthesis techniques starting from L = bond and E = heteroaryl (Scheme 40). Using a similar sequence, for building blocks where L = bond and E = heteroaryl, the appropriate R on the D ring can be added. 14 A heterocyclic E ring can also be formed from the group. [ka]

[0241] Alternatively, building blocks of formula 91 with L1 = -NHCH2- can be installed by reductive amination reaction of amine 92 with an appropriately 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., with TsOH when PG = Boc) (Scheme 41). [ka]

[0242] Alternatively, building blocks of formula 94, where L and L are bonded, B is a (hetero)aryl, and C is an N-linked cyclic amine, can be prepared by reacting an appropriately protected (spiro)cyclic amine (Y = I or Br) in two sequential cross-coupling reactions followed by deprotection. Most typically, this involves Ni-catalyzed cross-coupling between 69 (Y = I) and building block 79, which bears both bromide and boronic acid functionalities, to give bromo(hetero)aryl intermediate 95. Intermediate 95 could be coupled with amine 96 (e.g., under Buchwald conditions, Pd catalysis) followed by deprotection to give 94 (Scheme 42). [ka]

[0243] L1 and L2 = bond, C = (hetero)aryl and D = C3-C 10Cycloalkyl, 3- to 14-membered heterocyclyl-containing building blocks of formula 97 can be prepared by reacting appropriately protected (spiro)cyclic amines 69 (Y = I or Br) in two sequential cross-coupling reactions followed by deprotection. Most typically, this involves a Negishi cross-coupling of the zincate transiently generated from 69 (Y = I) with building block 98 bearing two bromide functionalities to give 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, generates building blocks of general formula 97 (Scheme 43). [ka]

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

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

[0246] Building blocks of formula 1 where C is a cyclic amine, D = (hetero)aryl, L = a bond, and L = a -CH- bond N-bonded to the D ring can be generated by reductive amination in a manner similar to that shown above.

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

[0248] In some cases, compounds of formula I can be further functionalized to provide other compounds of formula I. For example, compounds of formula I bearing (hetero)aryl bromides or iodides 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 installation 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 provide 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 reactions), conversion of boron-containing groups to hydroxyls using alkaline peroxide conditions, cycloaddition of azidotrimethylsilane with nitriles to generate tetrazoles, Sandmeyer reaction of anilines to bromides, oxidation of thioethers to sulfones, S N Building blocks can be generated from commercially available fragments using techniques such as alkylation of hydroxyl or amine groups via the 2 reaction or reductive amination, acylation using activated carbonyl derivatives, or installation of -SOMe or -SOCF groups from iodo- or bromo-building blocks using literature techniques. Such techniques can also be used to elaborate commercially available fragments before, after, or during the synthetic sequence described above.

[0250] Alternatively, particularly in the case of C=5-membered heteroaryls, the building blocks can be prepared from appropriately functionalized and protected A-ring precursors using standard heterocyclic synthesis techniques (see, for example, Heterocyclic Chemistry, Joule J. A. and Mills K., 5 th (See, Edition, Wiley, 2010). As an example: In the case of C=1,2,4-oxadiazole, the building block can be generated from the A ring bearing a carboxylic acid derivative via condensation / cyclization with an alkyl N-hydroxyacetamidine (which can be prepared from an alkylnitrile and hydroxylamine hydrochloride). Regioisomeric 1,2,4-oxadiazoles can also be generated by a similar method using an A ring bearing a nitrile group and a (halo)alkylcarboxylic acid. In the case of C=1,3,4-oxadiazole, the building block can be prepared from the A ring bearing a carboxylic acid derivative via generation 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 the A ring bearing an acetylene derivative and a (halo)alkylazide, temporarily generated from an amine via a cycloaddition reaction.

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

[0252] In one aspect, the present invention provides a method for preparing a compound of Formula (I) described herein, or a pharmaceutically acceptable salt thereof, the method being described in any one of Schemes 1-44.

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

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

[0255] In a further aspect, the present invention provides a compound of formula (I) as described herein for use in a method of inhibiting MAGL in a mammal.

[0256] In a further aspect, the present invention provides the use of a compound of formula (I) as described herein for the preparation of a medicament for inhibiting MAGL in a mammal.

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

[0258] Compounds of Formula (I) may be profiled for MAGL inhibitory activity by determining enzymatic activity following hydrolysis of the natural substrate, 2-arachidonoylglycerol (2-AG), to yield arachidonic acid, followed by mass spectrometry analysis. This assay is hereinafter abbreviated as the "2-AG assay."

[0259] Compounds of Formula (I) may be profiled for MAGL inhibitory activity by determining enzymatic activity following the hydrolysis of the natural substrate, 2-arachidonoylglycerol (2-AG), to generate arachidonic acid, followed by mass spectrometry. This assay is hereafter abbreviated as the "2-AG assay." The 2-AG assay was performed in a 384-well polypropylene assay plate. Compound dilutions were made in 3-fold dilutions in 100% DMSO in the polypropylene plate to give a final concentration range in the assay of 12.5 μM to 0.8 pM. Compound dilutions were added to 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 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-arachidonoylglycerol. After shaking and incubation at room temperature for 30 min, the reaction was stopped by adding two assay volumes of acetonitrile containing 4 μM d8-arachidonic acid. The amount of arachidonic acid formed was monitored by an online SPE system (Agilent Rapidfire) coupled 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, following the mass transitions of 303.1 → 259.1 for arachidonic acid and 311.1 → 267.0 for d8-arachidonic acid. Compound activity was calculated based on the intensity ratio [arachidonic acid / d8-arachidonic acid]. [Table 1] TIFF2024521618000161.tif249169 TIFF2024521618000162.tif248169 TIFF2024521618000163.tif248169 TIFF2024521618000164.tif248169 TIFF2024521618000165.tif248169 TIFF2024521618000166.tif248169 TIFF2024521618000167.tif248169 TIFF2024521618000168.tif249169 TIFF2024521618000169.tif248169 TIFF2024521618000170.tif244169 TIFF2024521618000171.tif244169 TIFF2024521618000172.tif245169 TIFF2024521618000173.tif245169 TIFF2024521618000174.tif245169 TIFF2024521618000175.tif62169

[0260] In one aspect, the present invention provides compounds of formula (I) as described herein, and pharmaceutically acceptable salts or esters thereof, wherein the compounds of formula (I) and pharmaceutically acceptable salts or esters thereof have an IC for MAGL inhibition as measured in the MAGL assay described herein. 50 is less than 25 μM, preferably less than 10 μM, more preferably less than 5 μM.

[0261] In one embodiment, the compounds of formula (I) described herein and their pharmaceutically acceptable salts or esters have an IC 50 (MAGL inhibition) values ​​range from 0.000001 μM to 25 μM, and certain compounds have IC 50 The IC values ​​are between 0.000005 μM and 10 μM, and certain compounds have IC 50 The value is between 0.00005 μM and 5 μM.

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

[0263] In a further aspect, the present invention provides the use of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for the treatment or prevention of neuroinflammation, neurodegenerative diseases, pain, cancer, and / or psychiatric disorders in a mammal.

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

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

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

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

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

[0269] In one aspect, the present invention provides the use of a compound of formula (I), as described herein, or a pharmaceutically acceptable salt 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, migraine, depression, hepatocellular carcinoma, colon carcinogenesis, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, and / or spasticity associated with pain in a mammal.

[0270] In a preferred embodiment, the present invention provides the use of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for the treatment or prevention of multiple sclerosis, Alzheimer's disease, and / or Parkinson's disease in a mammal.

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

[0272] In one aspect, the present invention provides a compound of formula (I), as described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of neuroinflammation, neurodegenerative diseases, pain, cancer, and / or psychiatric disorders in a mammal.

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

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

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

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

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

[0278] In one aspect, the present invention provides a compound of formula (I), as described herein, or a pharmaceutically acceptable salt 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 carcinogenesis, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, and / or spasticity associated with pain in a mammal.

[0279] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of multiple sclerosis, Alzheimer's disease, and / or Parkinson's disease in a mammal.

[0280] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of multiple sclerosis in a mammal.

[0281] In one aspect, the present invention provides the use of a compound of formula (I), as 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 psychiatric disorders in a mammal.

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

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

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

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

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

[0287] In a further aspect, the present invention provides the use of a compound of formula (I), as described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament 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 carcinogenesis, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, and / or spasticity associated with pain in a mammal.

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

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

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

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

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

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

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

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

[0296] In a further aspect, 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, spasticity associated with pain, abdominal pain, abdominal pain associated with irritable bowel syndrome, and / or visceral pain in a mammal, comprising administering to the mammal an effective amount of a compound of formula (I), as described herein, or a pharmaceutically acceptable salt thereof.

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

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

[0299] Pharmaceutical Compositions and Administration In one aspect, the present invention provides a pharmaceutical composition comprising a compound of formula (I) described herein and a therapeutically inert carrier.

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

[0301] The compounds of formula (I) and their pharmaceutically acceptable salts and esters can be used as medicines (e.g., in the form of pharmaceutical preparations). Pharmaceutical preparations can be administered to the body orally (e.g., in the form of tablets, coated tablets, dragees, hard and soft gelatin capsules, liquids, emulsions, or suspensions), nasally (e.g., in the form of nasal sprays), or rectally (e.g., in the form of suppositories). However, administration can also be carried out parenterally, such as intramuscularly or intravenously (e.g., in the form of injections).

[0302] The 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 its derivatives, talc, stearic acid or its salts, etc. can be used as adjuvants for tablets, sugar-coated tablets, and hard gelatin capsules, for example.

[0303] Suitable adjuvants for soft gelatin capsules are, for example, vegetable oils, waxes, fats, semisolid substances, and liquid polyols.

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

[0305] Suitable adjuvants for injection solutions are, for example, water, alcohols, polyols, glycerol, vegetable oils, etc.

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

[0307] In addition, pharmaceutical preparations may contain preservatives, solubilizers, viscosity-increasing substances, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavoring agents, salts for varying osmotic pressure, buffers, masking agents, or antioxidants. They may also contain still other therapeutically valuable substances.

[0308] Dosage can vary widely and can, of course, be adapted to the individual requirements of each particular 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 (for example, about 300 mg / person) will be appropriate, preferably divided into 1 to 3 individual doses, for example, of the same amount. However, it is clear that the upper limit given herein can be exceeded in indicated cases. [Example]

[0309] The present invention will be more fully understood by reference to the following examples, which, however, should not be construed as limiting the scope of the claims to the examples.

[0310] Where preparations are obtained as mixtures of enantiomers, the pure enantiomers can be separated by the methods 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 stated, all reactions and intermediates were prepared under an argon atmosphere.

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

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

[0314] Step a) (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(1H-1,2,4-triazol-1-yl)methanone

[0315] To a suspension of 6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane 2,2,2-trifluoroacetate A.1) (10.0 g, 31.4 mmol) in dry CHCl (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-triazol-1-yl)methanone (5.41 g, 33.0 mmol). The reaction mixture was stirred at 0 °C for 5 min and at room temperature for 30 min. The reaction mixture was diluted with dichloromethane and extracted with aqueous NaCO (1 M solution). The organic phase was collected, dried over sodium sulfate, and evaporated to dryness to give (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 the respective building blocks AX and BX. [Table 2] TIFF2024521618000178.tif252169 TIFF2024521618000179.tif245169 TIFF2024521618000180.tif219169 TIFF2024521618000181.tif249169 TIFF2024521618000182.tif253169 TIFF2024521618000183.tif234169 TIFF2024521618000184.tif46169

[0317] Example 3 [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone [ka]

[0318] To 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-oxadiazol-3-yl)benzoyl]-2-azaspiro[3.3]heptan-6-yl]methanesulfonate (83 mg, 200 μmol) in CHCN (2.0 mL) was added CsCO (600 μmol) in one portion in an 8 mL vial. The mixture was shaken at 100 °C for 16 h. The mixture was filtered and purified by preparative HPLC to give the title compound (23.9 mg, 28% yield). MS (ESI): m / z = 433.3 [M+H] +

[0319] Step a) [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-(6-hydroxy-2-azaspiro[3.3]heptan-2-yl)methanone

[0320] To a solution of 4-(5-tert-butyl-1,2,4-oxadiazol-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) was added HATU (8.80 g, 23.2 mmol) and TEA (6.25 g, 61.7 mmol, 8.59 mL). The reaction was stirred at 25 °C for 16 h. The solution was filtered and concentrated under reduced pressure at 40 °C. The residue was purified by flash silica gel chromatography (eluting with a 0-40% THF / petroleum ether gradient). The title compound (3.8 g, 10.0 mmol, 64.9% yield) 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-oxadiazol-3-yl)benzoyl]-2-azaspiro[3.3]heptan-6-yl]methanesulfonate

[0322] To a solution of [4-(5-tert-butyl-1,2,4-oxadiazol-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) was added MsCl (1.34 g, 11.7 mmol, 905 μL) dropwise at 0 °C. The resulting mixture was stirred at 0 °C for 2 h. The residue was poured into water (20 mL). The aqueous phase was extracted with DCM (20 mL × 3). The combined organic phases were dried over anhydrous NaSO, filtered, and concentrated in vacuo. The title compound (1.5 g, crude) was obtained as a yellow oil, 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 prepared using the respective heteroarene building block in the final step. In some cases, NaOtBu was used in place of Cs2CO3 in the final step. [Table 3] TIFF2024521618000187.tif238169 TIFF2024521618000188.tif224169

[0324] Example 20 1-[2-[4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)benzoyl]-2-azaspiro[3.3]heptan-6-yl]-1,2,4-triazole-3-carbonitrile [ka]

[0325] To a mixture of [4-(5-tert-butyl-1,2,4-oxadiazol-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) was added PS-PPh3 (600 μmol) in one portion in an 8 mL vial under N2. DIAD (260 μmol) was added to the mixture at 0 °C, and then the vial was capped and shaken at 30 °C for 16 h. The reaction mixture was filtered, and the solvent was concentrated by Speedvac. The residue was purified by preparative HPLC to give 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 each heteroarene building block. [Table 4]

[0327] Example 23 [4-(5-tert-butyl-1,2,4-oxadiazol-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-oxadiazol-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 under N atmosphere for 1 h to give a solution, which was added dropwise to a mixture of 5-bromo-2-methylpyridine (41 mg, 300 μmol), Pd(dba) (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 h. The solvent was removed under reduced pressure. The residue was washed with 1.5 mL of water and extracted with EtOAc (2 mL × 3). The organic layers were combined, dried over anhydrous Na2SO4, and concentrated to give a residue which was purified by preparative HPLC to give 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-oxadiazol-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-oxadiazol-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) was added imidazole (431 mg, 6.33 mmol) and triphenylphosphine (1.11 g, 4.22 mmol). The reaction mixture was stirred at 110 °C for 2 h. The solution was concentrated under reduced pressure at 50 °C. The residue was purified by flash silica gel chromatography eluting with a 0-100% DCM / petroleum ether gradient to afford the title compound (0.8 g, 1.60 mmol, 75.7% yield) as a white solid. MS (ESI): m / z = 452.1 [M+H] +

[0330] Example 30 [[6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-fluoro-6-[(1-methylcyclopropyl)methoxy]-3-pyridyl]methanone [ka]

[0331] To a solution of [6-(4-cyclopropylimidazol-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) in DMSO (1.0 mL) was added CsF (54.6 mg, 0.36 mmol). The mixture was stirred at 110 °C for 2 hours under microwave irradiation. The mixture was filtered and concentrated under reduced pressure to give a residue that was purified by preparative HPLC to give the title compound (24.1 mg, 0.052 mmol, 43.3% yield). MS (ESI): m / z = 411.2 [M+H] + .

[0332] Step a) [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-(5,6-difluoro-3-pyridyl)methanone

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

[0334] As in Example 30, the examples in the table below were generated using the respective building blocks in place of A.2. [Table 5]

[0335] Example 26 [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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) was added T3P (78.5 μL, 0.13 mmol). The mixture was stirred at 80° C. for 16 hours. The mixture was concentrated under reduced pressure to give a residue. The residue was purified by preparative HPLC to give the title compound (19.4 mg, 0.042 mmol, 35.0% yield). MS (ESI): m / z=466.2 [M+H] + .

[0337] Similar to Example 1, the examples in the table below were prepared using the respective building blocks AX and BX. Other exemplary coupling agents used include HATU, and other exemplary bases include DIPEA. [Table 6] TIFF2024521618000196.tif246169 TIFF2024521618000197.tif186169

[0338] Example 33 [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(trifluoromethoxy)phenyl]azetidin-1-yl]methanone [ka]

[0339] To a solution of [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-(3-iodoazetidin-1-yl)methanone (92.3 mg, 0.223 mmol) and (4-(trifluoromethoxy)phenyl)boronic acid (69.1 mg) in i-PrOH (3.00 mL) was added NiI (34.8 mg), trans-2-aminocyclohexanol hydrochloride (16.9 mg), and NaHMDS (0.446 mL, 1 M). The mixture was stirred at 80 °C for 16 h. The reaction mixture was concentrated by speedvac. The residue was purified by preparative HPLC (FA as a modifier) ​​to give 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) was added ethoxyethanetrifluoroborane; hydrogen fluoride (14.9 g, 45.9 mmol, 12.60 mL, 50-55% purity, 1.3 equiv.). The mixture was stirred at 25 °C for 16 h. The solvent was removed under reduced pressure, and 50 mL of DCM was added. The mixture was stirred at 25 °C for 30 min. The mixture was then filtered to give a white solid. The crude product 3-iodoazetidine (7.78 g, crude, HBF 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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-(3-iodoazetidin-1-yl)methanone

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

[0344] As with Example 33, commercially available boronic acid building blocks were used to generate the examples in the table below. [Table 7]

[0345] Example 35 6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(1,1-difluoroethyl)phenyl]azetidin-1-yl]methanone [ka]

[0346] To a solution of (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-iodoazetidin-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) was added aqueous CsCO (2.0 M, 335 μL, 0.669 mmol), CyJohn Phos (3.86 mg, 0.011 mmol), and Pd(dba) (10.2 mg, 0.011 mmol). The mixture was stirred at 80 °C for 16 h. The reaction mixture was concentrated by Speedvac. The residue was purified by preparative HPLC and then further purified by preparative TLC to give the title compound (13.4 mg). MS (ESI): m / z=428.2 [M+H] + .

[0347] Example 84 [3-[2-chloro-4-(trifluoromethoxy)phenyl]azetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone [ka]

[0348] A solution of 1-bromo-2-chloro-4-(trifluoromethoxy)benzene (CAS: 892845-59-9) (55.1 mg, 200 μmol) in DME (1.0 mL) was treated in a glove box with (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-iodoazetidin-1-yl)methanone ( 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 equiv.), dtbbpy (1.3 mg, 5 μmol, 0.05 equiv.), and (TMS)3SiH (37.2 mg, 150 μmol) were added. The mixture was stirred at 25 °C for 16 h under a 72 W blue LED strip. The mixture was filtered and washed with 1 mL of water. The mixture was then extracted with EtOAc (2 mL × 2). The organic layer was dried over anhydrous Na2SO4 and concentrated to give the crude product. The crude product was purified by preparative HPLC to give the title compound (16.4 mg). MS (ESI): m / z = 482.2 [M+H] + .

[0349] As with Example 84, commercially available bromide building blocks were used to generate the examples in the table below. [Table 8]

[0350] Example 40 [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane 4-methylbenzenesulfonate (A.1; salt) (40 mg, 106 μmol, equivalents: 1) in acetonitrile (100 μL) was added triethylamine (75.3 mg, 104 μL, 744 μmol) followed by di(1H-1,2,4-triazol-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 MgSO, filtered, and concentrated in vacuo to give a crude residue which was subjected to rpHPLC for purification to give 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 prepared using the respective building blocks AX and BX. In some cases, other salts of A.1 (e.g., trifluoroacetate) or alternative bases such as DIPEA were used. [Table 9] TIFF2024521618000205.tif238169 TIFF2024521618000206.tif214169 TIFF2024521618000207.tif123169

[0353] Example 42 6-(3-cyclopropyl-1,2,4-triazol-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) was added NaH (7.97 mg, 199 μmol), and the reaction mixture was stirred at room temperature for 10 minutes, followed by the addition of 2-(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl)-2-azaspiro[3.3]heptan-6-yl methanesulfonate (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 give 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-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(1H-1,2,4-triazol-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 h. Additional 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 was then again stirred at 80° C. for 6 h. The volatiles were removed in vacuo and the crude residue was purified by flash chromatography using an eluent mixture of dichloromethane and methanol (2%-15%) to give impure title compound (393 mg), which was purified again by flash chromatography (eluent mixture of heptane and 3:1 EtOAc:EtOH (60%-100%)) to give 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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl)-2-azaspiro[3.3]heptan-6-yl methanesulfonate

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

[0359] As with Example 42, commercially available phenol / alcohol building blocks were used to generate the examples in the table below. [Table 10] TIFF2024521618000210.tif102169

[0360] Example 55 [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[2-(trifluoromethyl)pyrimidin-4-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone [ka]

[0361] To a solution of (6-(3-cyclopropyl-1H-1,2,4-triazol-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 dry DMF (1 mL) was added NaH (7.34 mg, 183 μmol) under an inert atmosphere and 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 was directly subjected to reverse-phase HPLC purification to give the title compound (36.4 mg). MS (ESI): m / z=490.3 [M+H] + .

[0362] In a similar manner to Example 55, commercially available chloro-heteroaryl building blocks were used to generate the examples in the table below. [Table 11] TIFF2024521618000213.tif156169

[0363] Example 67 [6-(5-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone [ka]

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

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

[0366] To a solution of tert-butyl 6-(5-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate (the regioisomeric by-product produced in Example A.1, step b) (457 mg, 1.5 mmol) in DCM (12.2 mL) was added 2,2,2-trifluoroacetic acid (1.71 g, 1.15 mL, 15 mmol). The mixture was stirred at room temperature for 5 h. The solvent was removed, and TFA was coevaporated with toluene. The crude material 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-nitrophenyl carbonochloridate (303 mg, 1.5 mmol). The mixture was allowed to warm to room temperature and stirred for an additional 12 h. The solvent was removed under reduced pressure. The crude material was purified by column chromatography using heptane / ethyl acetate (1:1) as the solvent to give the title compound (195 mg, 528 μmol, 35.2% yield) as a pale yellow solid. MS (ESI): m / z=370.1 [M+H]+ .

[0367] Example 88 [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[4-[5-(2,2-dimethylpropyl)-1,2,4-oxadiazol-3-yl]phenyl]methanone [ka]

[0368] To a suspension of 4-(5-neopentyl-1,2,4-oxadiazol-3-yl)benzoic acid (B.32) (44.6 mg, 171 μmol) in dry DMF (1 mL) was added DIPEA (90.6 mg, 122 μL, 701 μmol) and HATU (65.2 mg, 171 μmol). The reaction mixture was stirred at room temperature for 15 minutes, followed by the addition of 6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane bis(4-methylbenzenesulfonate) (A.1; tosylate salt) (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 give the title compound (41.6 mg). MS (ESI): m / z = 447.4 [M+H]. + .

[0369] Example 90 [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(3-cyclobutyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone [ka]

[0370] To tert-butyl 6-(3-cyclobutyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate (165 mg, 518 μmol) in DCM (4.21 mL) was added TFA (591 mg, 399 μL, 5.18 mmol). The mixture was stirred at room temperature for 3 hours. The solvent was removed under reduced pressure, and 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-oxadiazol-3-yl)benzoic acid (128 mg, 518 μmol) and 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (1.32 g, 942 μL, 2.07 mmol). The mixture was stirred at room temperature for 14 h. 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 MgSO. The crude material was purified by column chromatography using DCM / methanol (0-10% methanol) as the solvent, followed by further purification using 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-Butyl 6-(3-cyclobutyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-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) was added cesium carbonate (2.65 g, 8.12 mmol), followed by 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 material was purified by HPLC to give the title compound as a white solid (170 mg, 26.3% yield). MS (ESI): m / z=319.3 [M+H] + .

[0373] Example 112 [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-[4-(difluoromethoxy)-2-fluoro-phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-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) was added TEA (2.64 mmol, 6.0 equiv). The mixture was cooled to 0 °C. Triphosgene (0.145 mmol, 0.33 equiv) in DCM (1 mL) was added to the mixture. The mixture was then stirred at 25 °C for 0.5 h. 6-(3-Cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane (A.1) (0.44 mmol) was added. The mixture was stirred at 25 °C for 2 h. The mixture was quenched with HO (2 mL), extracted with DCM (3 mL × 2), dried over anhydrous NaSO, and concentrated to give the crude product. The crude material was purified by preparative HPLC to give (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)((3aR,5s,6aS)-5-(4-(difluoromethoxy)-2-fluorophenoxy)hexahydrocyclopenta[c]pyrrol-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 equiv.) in DCM (5 mL) was added (3aR,5r,6aS)-tert-butyl 5-hydroxyhexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (100 mg, 0.44 mmol, 1.0 equiv.), PS-TPP (2.2 mmol, 5.0 equiv., 3 mmol / g), and DIAD (0.88 mmol, 2.0 equiv., 1.9 M in toluene) in a N2-filled glovebox. The mixture was shaken at 30 °C for 16 h and monitored by LCMS. The mixture was filtered, quenched with saturated aqueous NaHCO3 (2.0 mL), extracted with DCM (3.0 mL × 2), and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure to give 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 equiv.) in DCM (2 mL) was added 2 mL of HCl solution (8.0 mmol, 4.0 M in dioxane). The mixture was shaken at 30° C. for 2 h. The solvent was removed by Speedvac to give the crude title compound, which was used in the next step without purification. MS (ESI): m / z=288.1 [M+H] + .

[0379] Analogous to Example 112, the examples in the table below were prepared using the following commercially available phenolic building blocks in step a): [Table 12] TIFF2024521618000219.tif216169 TIFF2024521618000220.tif206169 TIFF2024521618000221.tif215169 TIFF2024521618000222.tif204169 TIFF2024521618000223.tif215169 TIFF2024521618000224.tif220169 TIFF2024521618000225.tif145169

[0380] Example 139 [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-[2-(difluoromethyl)phenyl]ethynyl]azetidin-1-yl]methanone [ka]

[0381] To a solution of 6-(4-cyclopropyl-1H-imidazol-1-yl)-2-azaspiro[3.3]heptane (A.2, free base) (35 mg, 172 μmol) in acetonitrile (1.98 mL) at 0 °C, Hunig's base (63 mg, 85.1 μL, 487 μmol) was added, followed by di(1H-1,2,4-triazol-1-yl)methanone (28.2 mg, 172 μmol). The reaction mixture was stirred at room temperature for 1 h. Hunig's base (63 mg, 85.1 μL, 487 μmol, equiv.: 4) was then 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 table below were prepared using the respective building blocks AX and BX. [Table 13]

[0383] Example 142 [6-(4-cyclopropylimidazol-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) was added (1-methylcyclopropyl)methanol (13.5 mg, 156 μmol) under inert conditions and at room temperature and stirred for 15 min. Then, a solution of (6-(4-cyclopropyl-1H-imidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-fluoro-5-methylpyridin-3-yl)methanone (26.6 mg, 78.1 μmol) in DMF (574 μL) was added, and the reaction was stirred at room temperature for 5.5 h. The mixture was diluted with EtOAc and washed with water, and the aqueous phase was then extracted with EtOAc. The combined organics were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography eluting with DCM:MeOH 100:0 to 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-imidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-fluoro-5-methylpyridin-3-yl)methanone

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

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

[0388] Example 146 [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(4-methylpyrazol-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-oxadiazol-3-yl)benzoic acid (CAS: 1119452-72-0) (110 mg, 0.450 mmol), and 6-(4-methylpyrazol-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 h. The mixture was purified by preparative HPLC (FA) and lyophilized to give the title compound (18.9 mg, 0.050 mmol, 10.2% yield) as a white solid. MS (ESI): m / z = 406.4 [M+H] +

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

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

[0392] To a solution of 6-(3-cyclopropyl-1,2,4-triazol-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) was added (4-nitrophenyl) 3-ethyl-3-methyl-4-[[1-(trifluoromethyl)cyclopropyl]methoxy]piperidine-1-carboxylate (55.8 mg, 0.130 mmol), and the mixture was stirred at 90 °C for 12 h. The mixture was concentrated, and the residue was purified by preparative HPLC (0.225% v / v FA) and lyophilized to give the title compound (10.6 mg, 0.020 mmol, 12.1% yield) 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) was added NaH (35.2 mg, 0.880 mmol) at 0° C. The reaction mixture was stirred for 30 min, then [1-(trifluoromethyl)cyclopropyl]methyl methanesulfonate (CAS: 1262400-04-3) (144 mg, 0.660 mmol) was added and the mixture was stirred at 50° C. for 12 h. The mixture was poured into saturated aqueous NH4Cl (10 mL) and extracted with EtOAc (3 mL, 3 times). The combined organic phase was washed with brine, dried over Na2SO4, and then concentrated. The residue was purified by silica gel column (PE: EtOAc = 30:1 to 20:1) to give the title compound (54 mg, 0.150 mmol, 35.1% yield) 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]octane trifluoroacetate

[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) was added TFA (0.1 mL, 0.140 mmol) in DCM (1 mL) at 0° C., and the mixture was then stirred at 25° C. for 1 h. The reaction mixture was concentrated under reduced pressure to give the title compound (50 mg, 0.140 mmol, 96.2% yield) 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) was added DIPEA (44.4 mg, 0.340 mmol) while maintaining the temperature at 0° C., followed by the addition of 8-[[1-(trifluoromethyl)cyclopropyl]methoxy]-5-azaspiro[2.5]octane trifluoroacetate (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: EtOAc = 2:1) to give the title compound (52.0 mg, 0.130 mmol, 91.2% yield) as a yellow oil. MS (ESI): m / z = 415.4 [M+H] +

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

[0400] Example 153 [6-(3-cyclopropyl-1,2,4-triazol-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) was added DIPEA (157 mg, 212 μL, 1.22 mmol) and HATU (121 mg, 319 μmol). The reaction mixture was stirred at room temperature for 10 min, followed by the addition of 6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane bis(4-methylbenzenesulfonate) (A.1, tosylate salt) (183 mg, 334 μmol). The reaction mixture was stirred at room temperature for 3 h. The crude reaction mixture was directly subjected to reverse-phase HPLC purification to give the title compound (78.9 mg, 49.4% yield). 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) under an inert atmosphere, potassium tert-butoxide (547 mg, 4.88 mmol) was added, and 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), after which the reaction was stirred at room temperature for 10 minutes. The reaction was then stirred at room temperature for 1 hour. Potassium tert-butoxide (124 mg, 1.11 mmol) was added, and the reaction mixture was again stirred at room temperature for 1 hour. The reaction mixture was then partitioned between ethyl acetate and HCl 1N aqueous solution. The organic phase was collected, and the aqueous phase was back-extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated in vacuo. The crude solution (residual DMSO) was then poured into a small amount of 1M aqueous HCl, causing precipitation to give a gummy solid. The entire fraction was then evaporated to dryness using a centrifugal evaporator to give the crude title compound, which was used in the next step without further purification (687 mg, 84.7% yield). MS (ESI): m / z = 330.1 [M + H] +

[0404] Example 154 [6-(3-cyclopropyl-1,2,4-triazol-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) was added DIPEA (85.5 mg, 116 μL, 662 μmol) and HATU (75.5 mg, 199 μmol). The reaction mixture was then stirred at room temperature for 10 minutes, followed by the addition of 6-(3-cyclopropyl-1H-1,2,4-triazol-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 give 77.2 mg of the desired product (85% purity). The previous fraction was again purified by SFC to give 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) under an inert atmosphere, NaH (83.8 mg, 2.1 mmol) was added, and the reaction mixture was stirred at room temperature for 5 minutes. Methyl 5-bromo-6-chloronicotinate (500 mg, 2 mmol) was then added, 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 aqueous NH4Cl solution, and the reaction mixture was diluted with ethyl acetate and subsequently washed with 1 M NaHCO3 solution. The organic phase was collected, and the aqueous phase was back-extracted with ethyl acetate. The combined organic phases were 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 give the title compound (577 mg, 80% yield). MS (ESI): m / z = 354.1 [M+H] +

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

[0409] To a solution of methyl 5-bromo-6-((1-(trifluoromethyl)cyclopropyl)methoxy)nicotinate (540 mg, 1.52 mmol) in dry DME (12 mL) under an inert atmosphere was added 3-bromooxetane (313 mg, 2.29 mmol), tris(trimethylsilyl)silane (379 mg, 470 μL, 1.52 mmol), (Ir[dF(CF)ppy](dtbpy))PF (17.1 mg, 15.2 μmol), and sodium carbonate (323 mg, 3.05 mmol). 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 the stirred suspension was added to the previous reaction mixture, and the reaction was stirred at room temperature under blue LED illumination for 18 hours. The reaction mixture was diluted with ethyl acetate and extracted with 1M aqueous NaCO3. The organic phase was collected, and the aqueous phase was back-extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and evaporated to dryness. The crude material was purified by flash chromatography eluting with a mixture of heptane and ethyl acetate (5%-60%) to give 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) was added 5.0 M aqueous NaOH (324 μL, 1.62 mmol), 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 collected, and the aqueous phase was back-extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and evaporated to dryness to give 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-triazol-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-triazol-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) was added NaH (1.94 mg, 0.08 mmol) at 0 °C, and the reaction mixture was stirred for 30 min. [1-(trifluoromethyl)cyclopropyl]methyl methanesulfonate (26.5 mg, 0.12 mmol) was added, and the mixture was stirred at 60 °C for 12 h. The reaction mixture was quenched by adding saturated aqueous NH4Cl (10 mL) at 0 °C, and then extracted with EtOAc (10 mL × 3). The combined organic phases were washed with brine (10 mL), dried over Na2SO4, concentrated in vacuo, purified by preparative HPLC (0.225% v / v FA), and then lyophilized to give 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-triazol-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-triazol-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 h. The residue was concentrated under reduced pressure and purified by reverse-phase flash chromatography to give the title compound (43.0 mg, 0.12 mmol, 57.5% yield) as a yellow oil. MS (ESI): m / z = 371.2 [M+H] +

[0416] Analogously to Example 155, the following examples were prepared using the respective heteroaryl building blocks of step a). [Table 17]

[0417] Example 156 [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(3-ethyl-1,2,4-triazol-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) was added TFA (624 mg, 422 μL, 5.47 mmol). The mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and TFA was coevaporated 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-oxadiazol-3-yl)benzoic acid (135 mg, 547 μmol) and 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 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 phases were dried over MgSO4, and the solvent was evaporated under reduced pressure. The crude material was initially purified by column chromatography eluting with DCM:methanol (10% methanol). The product-containing phase was subjected to rpHPLC for purification to give 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-triazol-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) was added cesium carbonate (3.35 g, 10.3 mmol), 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 phases were concentrated. The crude material was purified by SFC to give the title compound (160 mg, 547 μmol, 21.3% yield) as a colorless oil. MS (ESI): m / z=293.3 [M+H] + .

[0421] Analogously to Example 156, the following examples were prepared using the respective heteroaryl building blocks of step a). [Table 18]

[0422] Example 173 [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[1-(trifluoromethyl)cyclopropyl]methoxymethyl]cyclobutyl]methanone [ka]

[0423] To a solution of [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-(hydroxymethyl)cyclobutyl]methanone (30.0 mg, 0.09 mmol) in DMF (1 mL) was added NaH (2.28 mg, 0.09 mmol) at 0 °C and stirred for 30 min. Then, a solution of [1-(trifluoromethyl)cyclopropyl]methyl methanesulfonate (31.0 mg, 0.14 mmol) in DMF (1 mL) was added, and the reaction was stirred at 60 °C for 16 h. The reaction mixture was quenched by adding saturated aqueous NH4Cl (10 mL) at 0 °C. The mixture was extracted with EtOAc (10 mL × 3). The combined organic phases were washed with brine (10 mL), dried over Na2SO4, concentrated in vacuo, purified by preparative HPLC (0.225% v / v FA), and then lyophilized to give 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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-(hydroxymethyl)cyclobutyl]methanone

[0425] A solution of methyl 3-(hydroxymethyl)cyclobutanecarboxylate (CAS: 89941-55-9) (60.0 mg, 0.42 mmol), 6-(3-cyclopropyl-1,2,4-triazol-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 h. The reaction mixture was concentrated in vacuo, and the residue was purified by back-flash (0.05% FA condition) and then lyophilized to give the title compound (53.0 mg, 0.17 mmol, 40% yield) as a white solid. MS (ESI): m / z = 317.2 [M+H] +

[0426] Analogously to Example 173, the following examples were prepared using the respective building blocks of step a). [Table 19]

[0427] Example 177 (6-(3-(azetidin-1-yl)-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-(trifluoromethyl)benzyl)oxy)azetidin-1-yl)methanone [ka]

[0428] To a solution of (6-(3-bromo-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-(trifluoromethyl)benzyl)oxy)azetidin-1-yl)methanone (80 mg, 160 μmol) in dry DMSO (1 mL) was added azetidine (45.6 mg, 799 μmol), copper(I) iodide (7.61 mg, 40 μmol), L-proline (4.6 mg, 40 μmol), and CsCO (104 mg, 320 μmol). The reaction mixture was then stirred at 90° C. for 18 h. Copper(I) iodide (7.61 mg, 40 μmol), L-proline (4.6 mg, 40 μmol), CsCO (104 mg, 320 μmol), and 300 mg of azetidine were added, after which the reaction mixture was again stirred at 90° C. for 18 h. Insoluble material 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 give the title compound (17.5 mg). MS (ESI): m / z=477.3 [M+H] +

[0429] Step a) (6-(3-bromo-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-(trifluoromethyl)benzyl)oxy)azetidin-1-yl)methanone

[0430] To a suspension of di(1H-1,2,4-triazol-1-yl)methanone (471 mg, 2.87 mmol) in dry CHCN (6 mL) cooled to 0 °C under an inert atmosphere was slowly added a solution of 6-(3-bromo-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane (A.9) (665 mg, 2.74 mmol) and DIPEA (424 mg, 573 μL, 3.28 mmol) in dry CHCN (8 mL). The reaction was then stirred at 0 °C for 5 min and at room temperature for 1 h. Then, 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 then stirred at 80° C. for 18 hours. The reaction mixture was diluted with ethyl acetate and extracted with 1 M aqueous NaCO solution. The organic phase was collected and the aqueous phase was back-extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and evaporated to dryness. The crude material was purified by flash chromatography using an eluent mixture of dichloromethane and methanol (0% to 10%) to give the title compound (405 mg). MS (ESI): m / z=502.3 [M+H] +

[0431] Example 178 [6-(3-cyclopropyl-1,2,4-triazol-4-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(2-chloro-4-fluoro-phenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-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) was added TFA (92.6 mg, 62.6 μL, 812 μmol). The mixture was stirred at room temperature for 3 h. The solvent was evaporated under reduced pressure, and TFA was coevaporated 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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate (step b) (20 mg, 54.1 μmol) were added. The mixture was heated to 80°C for 24 hours. The solvent was removed under reduced pressure. The crude material was purified by column chromatography using DCM / methanol (0-10% methanol) as the solvent. The title compound (4 mg, 8.23 ​​µmol, 15% yield) 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-triazol-1-yl)-2-azaspiro[3.3]heptane-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) was added cesium carbonate (8.96 g, 27.5 mmol), followed by 3-cyclopropyl-1H-1,2,4-triazole (1.00 g, 9.16 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 solvent was removed under reduced pressure, and the crude material was purified by HPLC. The title compound (600 mg, 1.97 mmol, 22% yield) was obtained as a white solid. (Note: A by-product was obtained along with the regioisomer.) MS (ESI): m / z=305.2 [M+H] +

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

[0436] To a solution of tert-butyl 6-(5-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate (457 mg, 1.5 mmol) in DCM (12.2 mL) was added 2,2,2-trifluoroacetic acid (1.71 g, 1.15 mL, 15 mmol). The mixture was stirred at room temperature for 5 hours. The solvent was removed, and TFA was coevaporated with toluene. The crude material 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-nitrophenyl carbonochloridate (303 mg, 1.5 mmol). The mixture was allowed to warm to room temperature and stirred for an additional 12 hours. The solvent was removed under reduced pressure. The crude material was purified by column chromatography using heptane / ethyl acetate (1:1) as the solvent to give 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) was added triphenylphosphine (266 mg, 1.01 mmol), 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 allowed to warm to room temperature and stirred for 24 h. The reaction was quenched by adding saturated aqueous NaCO (10 mL). The aqueous phase was extracted with DCM (3 × 20 mL). The organic phase was washed with aqueous NaOH (30 mL, 1 M) and brine. The organic phase was dried over MgSO4 and the solvent was evaporated under reduced pressure. The crude material 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-oxadiazol-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-oxadiazol-3-yl)benzoic acid (99.5 mg, 404 μmol) in DMF (1 mL) was added DIPEA (348 mg, 470 μL, 2.69 mmol), followed by 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (685 mg, 489 μL, 1.08 mmol). 6-(2-Cyclopropyloxazol-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 was stirred at room temperature for 5 h. The mixture was diluted with ethyl acetate and washed with water. The aqueous phase was extracted twice with ethyl acetate. The combined organic phase was washed with water and brine and dried over MgSO4. The solvent was evaporated under reduced pressure. The crude material was purified by rpHPLC. The title compound (17 mg, 36.4 μmol, 14% yield) 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]heptane-2-carboxylate

[0442] A solution of 2-cyclopropyloxazole (114 mg, 1.04 mmol) in anhydrous THF (3.5 mL) was cooled to 0 °C. n-Butyllithium (710 μL, 1.14 mmol, equivalents: 1.2) was added dropwise over 10 minutes. The mixture was stirred for 30 minutes. tert-Butyl 6-oxo-2-azaspiro[3.3]heptane-2-carboxylate (200 mg, 947 μmol) in dry THF (1.23 mL) was added dropwise. The mixture was stirred at 0 °C for 2 hours. The mixture was poured onto ice. The mixture was extracted twice with ethyl acetate. The organic phase was washed with water and brine and dried over MgSO4. The solvent was removed under reduced pressure. The crude material was purified by column chromatography using ethyl acetate as the solvent. The title compound (87 mg, 239 μmol, 25% yield) was obtained as a pale brown oil. MS (ESI): m / z = 321.3 [M+H]+

[0443] Step b) 6-(2-cyclopropyloxazol-5-yl)-2-azaspiro[3.3]heptan-6-ol 2,2,2-trifluoroacetate

[0444] To a solution of tert-butyl 6-(2-cyclopropyloxazol-5-yl)-6-hydroxy-2-azaspiro[3.3]heptane-2-carboxylate (87 mg, 272 μmol) in DCM (1.36 mL) was added 2,2,2-trifluoroacetic acid (464 mg, 318 μL, 4.07 mmol). The mixture was stirred at room temperature for 4 hours. The solvent was evaporated under reduced pressure, and TFA was co-evaporated with toluene. The title compound (90 mg, 240 μmol, 88% yield) was obtained as an off-white oil. MS (ESI): m / z = 221.2 [M+H] +

[0445] Example 181 [3-(1-tert-butylpyrazol-4-yl)azetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone [ka]

[0446] To a solution of 4-bromo-1-(tert-butyl)-1H-pyrazole (98.3 mg, 0.484 mmol) in DME (5.0 mL) was added (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-iodoazetidin-1-yl)methanone (Example 33, step b) (200 mg, 0.484 mmol), PMP (301 mg, 1.94 mmol), Ir[dF(CF)ppy](dtbbpy)PF (5.4 mg, 4.84 μmol), NiCl.DME (5.3 mg, 24.2 μmol), dtbbpy (6.5 mg, 24.2 μmol), and (TES)SiH (181 mg, 0.484 mmol) in a glove box. The mixture was stirred at room temperature (25°C) for 48 hours under irradiation with a 72W blue LED strip. The mixture was filtered and washed with 1 mL of water. The mixture was then extracted with EtOAc (2 mL x 2). The organic layer was dried over anhydrous Na2SO4 and concentrated to give the crude product. The crude product was purified by preparative HPLC to give the title compound (7.64 mg). MS (ESI): m / z = 410.3 [M + H] + .

[0447] As with Example 181, commercially available bromide building blocks were used to generate the examples in the table below. [Table 20]

[0448] Example 447 [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone [ka]

[0449] To a solution of 6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane; 2,2,2-trifluoroacetic acid (A.1) (40 mg, 0.126 mmol) in N,N-dimethylformamide (0.645 mL) cooled to 0 ° C., DIPEA (154 μL, 0.880 mmol) was added, followed by bis(1,2,4-triazol-1-yl)methanone (21.7 mg, 0.132 mmol), after which the reaction mixture was stirred at 0 ° C. for 30 min. This was followed by [3-(2-azaspiro[3.3]heptan-6-ylmethyl)phenyl]-imino-keto-(trifluoromethyl)-λ 6 -sulfane;tosylate (D.1) (64.7 mg, 0.132 mmol) was added to the reaction mixture, which was then stirred at 50° C. for 18 hours. The crude reaction mixture was directly subjected to reverse-phase HPLC purification to give 24.8 mg of the title compound as a white solid. MS (ESI): m / z=549.4 [M+H] +

[0450] Similar to Example 1, the examples in the following table were prepared using the respective building blocks AX and DX. In some cases (marked with *), the reaction was carried out using the isolated [6-(5-cyclopropyl-4H-1,2,4-triazol-3-yl)-2-azaspiro[3.3]heptan-2-yl]-(1,2,4-triazol-1-yl)methanone intermediate. In some cases, TEA can be used instead of DIPEA, and DMF and ACN can be used interchangeably as solvents. [Table 21] TIFF2024521618000249.tif243169 TIFF2024521618000250.tif252169 TIFF2024521618000251.tif252169 TIFF2024521618000252.tif249169 TIFF2024521618000253.tif206169 TIFF2024521618000254.tif249169 TIFF2024521618000255.tif243169 TIFF2024521618000256.tif247169 TIFF2024521618000257.tif240169 TIFF2024521618000258.tif225169 TIFF2024521618000259.tif233169 TIFF2024521618000260.tif221169 TIFF2024521618000261.tif213169 TIFF2024521618000262.tif218169 TIFF2024521618000263.tif213169 TIFF2024521618000264.tif203169 TIFF2024521618000265.tif232169 TIFF2024521618000266.tif222169 TIFF2024521618000267.tif222169 TIFF2024521618000268.tif220169 TIFF2024521618000269.tif217169 TIFF2024521618000270.tif229169 TIFF2024521618000271.tif213169 TIFF2024521618000272.tif208169 TIFF2024521618000273.tif237169 TIFF2024521618000274.tif218169 TIFF2024521618000275.tif204169 TIFF2024521618000276.tif233169 TIFF2024521618000277.tif208169 TIFF2024521618000278.tif218169 TIFF2024521618000279.tif212169 TIFF2024521618000280.tif209169 TIFF2024521618000281.tif208169 TIFF2024521618000282.tif219169 TIFF2024521618000283.tif208169 TIFF2024521618000284.tif217169 TIFF2024521618000285.tif209169 TIFF2024521618000286.tif218169 TIFF2024521618000287.tif214169 TIFF2024521618000288.tif212169 TIFF2024521618000289.tif219169 TIFF2024521618000290.tif252169 TIFF2024521618000291.tif252169 TIFF2024521618000292.tif238169 TIFF2024521618000293.tif253169 TIFF2024521618000294.tif234169 TIFF2024521618000295.tif147169

[0451] Example 214 and Example 216

[0452] [6-(3-Cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(3R)-3-hydroxy-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidin-1-yl]methanone (Example 214) and [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(3S)-3-hydroxy-3-(trifluoromethyl)pyrrolidino]-3-pyridyl]azetidin-1-yl]methanone (Example 216) [ka]

[0453] Example 212 (120 mg, 0.23 mmol) was purified by chiral SFC to give Example 214 (58.8 mg, 27% yield) and Example 216 (55.7 mg, 27.1% yield). Stereochemistry was arbitrarily assigned. MS (ESI): m / z = 518.3 [M+H] + (for both enantiomers)

[0454] Example 239 [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(2,2-dimethylpropylsulfonyl)-2,6-diazaspiro[3.3]heptan-6-yl]methanone [ka]

[0455] To a solution of [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-(2,6-diazaspiro[3.3]heptan-2-yl)methanone; 2,2,2-trifluoroacetic acid (150 mg, 0.189 mmol) in dichloromethane (1.5 mL) was added DIPEA (164.3 μL, 0.943 mmol) and 2,2-dimethylpropane-1-sulfonyl chloride (33.8 mg, 0.198 mmol). The mixture was stirred at 23 °C for 18 h and then evaporated. Purification by RP-HPLC afforded the title compound (29.4 mg, 33%). MS (ESI): m / z = 463.4 [M+H] +

[0456] Step a): (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(1H-1,2,4-triazol-1-yl)methanone

[0457] To a suspension of 6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane 2,2,2-trifluoroacetate (A.1; 18 g, 56.6 mmol) in dry CHCl (240 ml) cooled to 0 °C, DIPEA (29.6 mL, 170 mmol) (white suspension) was added, followed by CDT (9.75 g, 59.4 mmol). The mixture was stirred for 5 min at 0 °C for 5 min and at 23 °C for 45 min, then diluted with DCM. The mixture was extracted with 1 M aqueous NaCO. The combined organic layers were dried over NaSO, filtered, and evaporated to give the title compound (16.59 g, 98% yield). MS (ESI): m / z = 300.2 [M+H] +

[0458] Step b): 6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester

[0459] To a solution of [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-(1,2,4-triazol-1-yl)methanone (4 g, 13.36 mmol) in DMF (50 mL) was added 2,6-diazaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester; oxalic acid (3.38 g, 6.95 mmol) and DIPEA (4....

Claims

1. Formula (I) 【Chemistry 1】 (In the formula, X is CR ８ or N, A is, 【Chemistry 2】 is selected from B is B-1 to B-10: 【Chemistry 3】 (The wavy line indicates the point of attachment to the remainder of formula (I)) is a heteroaryl selected from C is C ６ ~C １４ Aryl, 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 aryl, and 5- to 14-membered heteroaryl; E is C ３ ~C １０ cycloalkyl, and 3- to 14-membered heterocyclyl; 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 N.H.C.H. ２ --, --CH ２ N.H.S.O. ２ -, -SO ２ --, --CH ２ SO ２ -, -SO ２ CH ２ -, -(CH ２ ) ２ SO ２ -, -SO ２ (CH ２ ) ２ is selected from -, carbonyl, -NHC(O)-, and -C(O)NH-; L ２ is a covalent bond, -CH ２ --, --CH ２ NH-, -NHCH ２ -, -NH-, -N(C １ ~C ６ Alkyl)- and -SO ２ - selected from L ３ represents a covalent bond and -CH ２ - selected from R １ is hydrogen, halogen, R １ is hydrogen, halogen, 【Chemistry 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 -, Halo-C １ ~C ６ Alkyl-S(O) ２ -, (C １ ~C ６ Alkyl) ２ N-SO ２ - and halo-C １ ~C ６ alkyl-C(O)-; R ２ , R ３ , and R ４ are each independently hydrogen, halogen, or C １ ~C ６ Alkyl, halo-C １ ~C ６ alkyl, and 3- to 14-membered heterocyclyl; R ５ and R ６ are each independently hydrogen, halogen, cyano, hydroxy, amino, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, halo-C １ ~C ６ Alkyl, halo-C １ ~C ６ Alkoxy, C ３ ~C １０ cycloalkyl, and 3- to 14-membered heterocyclyl; ３ ~C １０ Cycloalkyl and 3- to 14-membered heterocyclyl are C １ ~C ６ Alkyl, halo-C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, halo-C １ ~C ６ optionally substituted with 1, 2 or 3 substituents selected from alkoxy, halogen, cyano, amino and hydroxy; R ７ is absent or is 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 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 -, Halo-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 -, carbamoyl, C １ ~C ６ Alkyl-C(O)NH-, halo-C １ ~C ６ alkyl-NHC(O)-, oxo, 【Chemistry 6】 【Chemistry 7】 and 【Chemistry 8】 is selected from R １０ and R １１ are each independently hydrogen, halogen, cyano, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, halo-C １ ~C ６ alkyl, and oxo; R １２ is hydrogen, carbamoyl, C １ ~C ６ Alkyl-NHC(O)- and halo-C ６ ~C １４ aryl; R １３ is hydrogen, or R １２ and R １３ together with the carbon atom to which they are attached, ３ ~C １０ Forming a cycloalkyl, 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】 is selected from R １５ is hydrogen, halogen, hydroxy, oxo, C １ ~C ６ alkyl, R １６ is selected from hydrogen and halogen; R １７ is hydrogen, C １ ~C ６ Alkyl and halo-C １ ~C ６ alkyl) or a pharma- ceutically acceptable salt thereof.

2. X is CR ８ and A, 【Chemistry 10】 is selected from B is B-1 to B-6: 【Chemistry 11】 (The wavy line indicates the point of attachment to the remainder of formula (I)) is a heteroaryl selected from C, C ６ ~C １４ Aryl, C ３ ~C １０ selected from cycloalkyl, 5- to 6-membered heteroaryl, and 3- to 14-membered heterocyclyl; L １ が, shared combination, -CR １２ R １３ -, -CH ２ O-、-OCH ２ -, -CH ２ NH-、-NHCH ２ -, -CH ２ OCH ２ -, -O-, -NH-, 【Chemistry 12】 -SO ２ NH-, -NHSO ２ -, -SO ２ N.H.C.H. ２ --, --CH ２ N.H.S.O. ２ -, -SO ２ --, --CH ２ SO ２ -, -SO ２ CH ２ -, -(CH ２ ) ２ SO ２ -, -SO ２ (CH ２ ) ２ is selected from -, carbonyl, -NHC(O)-, and -C(O)NH-; R １ But hydrogen, halogens, 【Chemistry 13】 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 -, Halo-C １ ~C ６ Alkyl-S(O) ２ -, (C １ ~C ６ Alkyl) ２ N-SO ２ - and halo-C １ ~C ６ alkyl-C(O)-; R ２ , R ３ , and R ４ are each independently hydrogen, halogen, or C １ ~C ６ Alkyl, halo-C １ ~C ６ alkyl, and 3- to 14-membered heterocyclyl; R ５ and R ６ are each independently hydrogen, halogen, cyano, hydroxy, amino, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, halo-C １ ~C ６ Alkyl, halo-C １ ~C ６ Alkoxy, C ３ ~C １０ cycloalkyl, and 3- to 14-membered heterocyclyl; ３ ~C １０ Cycloalkyl and 3- to 14-membered heterocyclyl are C １ ~C ６ Alkyl, halo-C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, halo-C １ ~C ６ optionally substituted with 1, 2 or 3 substituents selected from alkoxy, halogen, cyano, amino and hydroxy; R ７ is absent or is selected from 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 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 ３ ~C １０ Cycloalkyl, C ３ ~C １０ Cycloalkyl-C １ ~C ６ Alkyl-, 3- to 14-membered heterocyclyl, C ６ ~C １４ Aryl, C １ ~C ６ Alkyl-SO ２ -, 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 -, carbamoyl, C １ ~C ６ Alkyl-C(O)NH-, halo-C １ ~C ６ is selected from alkyl-NHC(O)- and oxo; ３ ~C １０ Cycloalkyl, 3- to 14-membered heterocyclyl, and C ６ ~C １４ Aryl is C １ ~C ６ Alkyl, halo-C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, halo-C １ ~C ６ optionally substituted with 1, 2, or 3 substituents selected from alkoxy, 3- to 14-membered heterocyclyl, halogen, cyano, amino, and hydroxy; R １０ and R １１ are each independently hydrogen, halogen, cyano, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, halo-C １ ~C ６ alkyl, and oxo; R １２ is hydrogen, carbamoyl, C １ ~C ６ Alkyl-NHC(O)- and halo-C ６ ~C １４ aryl; R １３ is hydrogen, or R １２ and R １３ together with the carbon atom to which they are attached, C ３ ~C １０ forming a cycloalkyl, 2. A compound of formula (I) according to claim 1, or a pharma- ceutically acceptable salt thereof.

3. A, 【Chemistry 14】 is selected from C, C ６ ~C １４ Aryl, 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 aryl, and 5- to 14-membered heteroaryl; E is C ３ ~C １０ cycloalkyl, and 3- to 14-membered heterocyclyl; 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 N.H.C.H. ２ --, --CH ２ N.H.S.O. ２ -, -SO ２ --, --CH ２ SO ２ -, -(CH ２ ) ２ SO ２ -, carbonyl, and -C(O)NH-; L ２ is a covalent bond, -CH ２ --, --CH ２ NH-, -NHCH ２ -, -NH-, -N(C １ ~C ６ Alkyl)- and -SO ２ - selected from L ３ is a covalent bond and -CH ２ - selected from R １ but, 【Chemistry 16】 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 -, Halo-C １ ~C ６ Alkyl-S(O) ２ -, (C １ ~C ６ Alkyl) ２ N-SO ２ - and halo-C １ ~C ６ alkyl-C(O)-; R ２ But hydrogen, halogen, C １ ~C ６ Alkyl, halo-C １ ~C ６ alkyl, and 3- to 14-membered heterocyclyl; R ３ is selected from hydrogen and halogen; R ４ is hydrogen, 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 -, Halo-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 -, carbamoyl, C １ ~C ６ Alkyl-C(O)NH-, halo-C １ ~C ６ alkyl-NHC(O)-, oxo, 【Chemistry 17】 【Chemistry 18】 and 【Chemistry 19】 is selected from C ３ ~C １０ Cycloalkyl, 3- to 14-membered heterocyclyl and C ６ ~C １４ Aryl is halo-C １ ~C ６ optionally substituted with 1 or 2 substituents selected from alkyl, 3- to 14-membered heterocyclyl, halogen and hydroxy; R １０ is hydrogen, halogen, cyano, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, halo-C １ ~C ６ alkyl, and oxo; R １１ is selected from hydrogen and halogen; R １２ is hydrogen, carbamoyl, C １ ~C ６ Alkyl-NHC(O)- and halo-C ６ ~C １４ aryl; R １３ is hydrogen, or R １２ and R １３ together with the carbon atom to which they are attached, C ３ ~C １０ Forming a cycloalkyl, 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 20】 is selected from R １５ is hydrogen, halogen, hydroxy, oxo, and C １ ~C ６ alkyl, R １６ is selected from hydrogen and halogen; R １７ is hydrogen, C １ ~C ６ Alkyl and halo-C １ ~C ６ selected from alkyl, 3. A compound of formula (I) according to claim 1 or 2, or a pharma- ceutically acceptable salt thereof.

4. A, 【Chemistry 21】 4. The compound of formula (I) according to claim 3, selected from:

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, C ６ ~C １４ Aryl, C ３ ~C １０ cycloalkyl, and 5- to 14-membered heteroaryl; D is C ３ ~C １０ selected from cycloalkyl and 3- to 14-membered heterocyclyl; L １ is a covalent bond, -CR １２ R １３ --, --CH ２ O-, -O-, -SO ２ NH- and -SO ２ - selected from L ２ is a covalent bond and -CH ２ - selected from R １ but, 【Chemistry 22】 and R ２ is hydrogen and C １ ~C ６ alkyl, R ３ , R ４ , R １２ , and R １３ are all hydrogen, R ９ But 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】 is selected from R １０ is hydrogen, halogen, haloC １ ~C ６ Alkyl, and C １ ~C ６ alkoxy; R １１ is selected from hydrogen and halogen; R １４ is hydrogen and halo-C １ ~C ６ alkyl, R １５ is selected from hydrogen and hydroxy; R １６ is hydrogen, 4. A compound of formula (I) according to claim 3, or a pharma- ceutically acceptable salt thereof.

6. 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, azetidinyl and pyrrolidinyl; L １ is a covalent bond, -CR １２ R １３ --, --CH ２ O-, -O-, -SO ２ NH- and -SO ２ - selected from L ２ is a covalent bond and -CH ２ - selected from R １ but, 【Chemistry 26】 and R ２ is selected from hydrogen and methyl; R ３ , R ４ , R １２ , and R １３ are all hydrogen, R ９ Fluoro, chloro, tert-butyl, CF ３ , C.F. ３ O.S.F. ５ , methylsulfonyl, 【Chemical 27】 【Chemistry 28】 and 【Chemical Formula 29】 is selected from R １０ is hydrogen, fluoro, chloro, CF ３ and methoxy; R １１ is selected from hydrogen and fluoro; R １４ but hydrogen and CF ３ is selected from R １５ is selected from hydrogen and hydroxy; R １６ is hydrogen, 6. A compound of formula (I) according to claim 5, or a pharma- ceutically acceptable salt thereof.

7. B is B-1 to B-10: 【Chemistry 30】 (The wavy line indicates the point of attachment to the remainder of formula (I)) is a heteroaryl selected from R ５ is hydrogen, halogen, cyano, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, halo-C １ ~C ６ Alkyl, C ３ ~C １０ cycloalkyl, and 3- to 14-membered heterocyclyl; ３ ~C １０ Cycloalkyl is hydroxy and C １ ~C ６ is optionally substituted with one substituent selected from alkyl; R ６ is selected from hydrogen and halogen; R ７ is absent or is hydrogen; 3. A compound of formula (I) according to claim 1 or 2, or a pharma- ceutically acceptable salt thereof.

8. B, 【Chemistry 31】 (The wavy line indicates the point of attachment to the remainder of formula (I)) and R ５ But, C １ ~C ６ Alkyl, halo-C １ ~C ６ Alkyl, and C ３ ~C １０ cycloalkyl, wherein C ３ ~C １０ The cycloalkyl is optionally substituted with one hydroxy substituent; R ６ is hydrogen, R ７ But it doesn't exist, 8. A compound of formula (I) according to claim 7, or a pharma- ceutically acceptable salt thereof.

9. B, 【Chemistry 32】 (The wavy line indicates the point of attachment to the remainder of formula (I)) and R ５ But ethyl, CF ３ and cyclopropyl, which is optionally substituted with one hydroxy substituent; R ６ is hydrogen, R ７ But it doesn't exist, 9. A compound of formula (I) according to claim 8, or a pharma- ceutically acceptable salt thereof.

10. X is CR ８ or N, R ８ is hydrogen or hydroxy; 3. A compound of formula (I) according to claim 1 or 2, or a pharma- ceutically acceptable salt thereof.

11. X is CR ８ and R ８ is hydrogen, 11. A compound of formula (I) according to claim 10, or a pharma- ceutically acceptable salt thereof.

12. X is CR ８ or N, A, 【Chemical 33】 is selected from B is B-1 to B-10: 【Chemical 34】 (The wavy line indicates the point of attachment to the remainder of formula (I)) is a heteroaryl selected from C, C ６ ~C １４ Aryl, 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 aryl, and 5- to 14-membered heteroaryl; E is C ３ ~C １０ cycloalkyl, and 3- to 14-membered heterocyclyl; 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 N.H.C.H. ２ --, --CH ２ N.H.S.O. ２ -, -SO ２ --, --CH ２ SO ２ -, -(CH ２ ) ２ SO ２ -, carbonyl, and -C(O)NH-; L ２ is a covalent bond, -CH ２ --, --CH ２ NH-, -NHCH ２ -, -NH-, -N(C １ ~C ６ Alkyl)- and -SO ２ - selected from L ３ is a covalent bond and -CH ２ - selected from R １ but, 【Chemical 36】 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 -, Halo-C １ ~C ６ Alkyl-S(O) ２ -, (C １ ~C ６ Alkyl) ２ N-SO ２ - and halo-C １ ~C ６ alkyl-C(O)-; R ２ But hydrogen, halogen, C １ ~C ６ Alkyl, halo-C １ ~C ６ alkyl, and 3- to 14-membered heterocyclyl; R ３ is selected from hydrogen and halogen; R ４ is hydrogen, R ５ is hydrogen, halogen, cyano, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, halo-C １ ~C ６ Alkyl, C ３ ~C １０ cycloalkyl, and 3- to 14-membered heterocyclyl; ３ ~C １０ Cycloalkyl is hydroxy and C １ ~C ６ is optionally substituted with one substituent selected from alkyl; R ６ is selected from hydrogen and halogen; R ７ is absent or is hydrogen, R ８ is hydrogen or 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 -, Halo-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 -, carbamoyl, C １ ~C ６ Alkyl-C(O)NH-, halo-C １ ~C ６ alkyl-NHC(O)-, oxo, 【Chemical 37】 【Chemical Formula 38】 and 【Chemical Formula 39】 is selected from R １０ is hydrogen, halogen, cyano, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, halo-C １ ~C ６ alkyl, and oxo; R １１ is selected from hydrogen and halogen; R １２ is hydrogen, carbamoyl, C １ ~C ６ Alkyl-NHC(O)- and halo-C ６ ~C １４ aryl; R １３ is hydrogen, or R １２ and R １３ together with the carbon atom to which they are attached, C ３ ~C １０ Forming a cycloalkyl, 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 - and 【Chemistry 40】 is selected from R １５ is hydrogen, halogen, hydroxy, oxo, and C １ ~C ６ alkyl, R １６ is selected from hydrogen and halogen; R １７ is hydrogen, C １ ~C ６ Alkyl and halo-C １ ~C ６ selected from alkyl, 2. A compound of formula (I) according to claim 1, or a pharma- ceutically 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; B, 【Chemistry 41】 (The wavy line indicates the point of attachment to the remainder of formula (I)) and C, C ６ ~C １４ Aryl, C ３ ~C １０ cycloalkyl, and 5- to 14-membered heteroaryl; D is C ３ ~C １０ selected from cycloalkyl and 3- to 14-membered heterocyclyl; L １ is a covalent bond, -CR １２ R １３ --, --CH ２ O-, -O-, -SO ２ NH- and -SO ２ - selected from L ２ is a covalent bond and -CH ２ - selected from R １ but, 【Chemistry 42】 and R ２ is hydrogen and C １ ~C ６ alkyl, R ３ , R ４ , R ６ , R ８ , R １２ and R １３ are all hydrogen, R ５ But, C １ ~C ６ Alkyl, halo-C １ ~C ６ Alkyl, and C ３ ~C １０ cycloalkyl, wherein C ３ ~C １０ The cycloalkyl is optionally substituted with one hydroxy substituent; R ７ But it doesn't exist. R ９ But 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】 is selected from R １０ is hydrogen, halogen, haloC １ ~C ６ Alkyl, and C １ ~C ６ alkoxy; R １１ is selected from hydrogen and halogen; R １４ is hydrogen and halo-C １ ~C ６ alkyl, R １５ is selected from hydrogen and hydroxy; R １６ is hydrogen, 13. A compound of formula (I) according to claim 12, or a pharma- ceutically acceptable salt thereof.

14. 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 line indicates the point of attachment to the remainder of formula (I)) and C is selected from phenyl, cyclopropyl, pyridyl, 1,2,4-oxadiazolyl, pyrazinyl, and pyrimidinyl; D is selected from cyclopropyl, azetidinyl and pyrrolidinyl; L １ is a covalent bond, -CR １２ R １３ --, --CH ２ O-, -O-, -SO ２ NH- and -SO ２ - selected from L ２ is a covalent bond and -CH ２ - selected from R １ but, 【Chemistry 47】 and R ２ is selected from hydrogen and methyl; R ３ , R ４ , R ６ , R ８ , R １２ and R １３ are all hydrogen, R ５ But ethyl, CF ３ and cyclopropyl, which is optionally substituted with one hydroxy substituent; R ７ does not exist, R ９ Fluoro, chloro, tert-butyl, CF ３ , C.F. ３ O.S.F. ５ , methylsulfonyl, 【Chemistry 48】 【Chemistry 49】 and 【Chemistry 50】 is selected from R １０ is hydrogen, fluoro, chloro, CF ３ and methoxy; R １１ is selected from hydrogen and fluoro; R １４ but hydrogen and CF ３ is selected from R １５ is selected from hydrogen and hydroxy; R １６ is hydrogen, 14. A compound of formula (I) according to claim 13, or a pharma- ceutically acceptable salt thereof.

15. (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)azetidin-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(3-((1-(trifluoromethyl)cyclopropyl)methyl)-1,2,4-oxadiazol-5-yl)azetidin-1-yl)methanone; (4-(5-(tert-butyl)-1,2,4-oxadiazol-3-yl)phenyl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (4-(5-(tert-butyl)-1,2,4-oxadiazol-3-yl)phenyl)(6-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-[3-(trifluoromethyl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(4-chloropyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(4-cyclopropylpyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 1-[2-[4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)benzoyl]-2-azaspiro[3.3]heptan-6-yl]pyrazole-3-carbonitrile; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-[3-(1-methylcyclopropyl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-[5-(1-methylcyclopropyl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(4-methoxypyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(4,5,6,7-tetrahydroindazol-2-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(3-methoxypyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(6,7-dihydro-4H-pyrano[4,3-c]pyrazol-2-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(4-fluoropyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-[5-(trifluoromethyl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(5-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(6,7-dihydro-4H-pyrano[4,3-c]pyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(5-methoxypyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 1-[2-[4-(5-tert-butyl-1,2,4-oxadiazol-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-oxadiazol-3-yl)benzoyl]-2-azaspiro[3.3]heptan-6-yl]pyrazole-4-carbonitrile; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(4,5,6,7-tetrahydroindazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(6-methyl-3-pyridyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-methyl-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone; [6-(4-cyclopropylimidazol-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-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-methyl-5-[[1-(trifluoromethyl)cyclopropyl]methoxy]pyrazin-2-yl]methanone; [6-(4-cyclopropylimidazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-fluoro-6-[(1-methylcyclopropyl)methoxy]-3-pyridyl]methanone; [[6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-fluoro-6-[(1-methylcyclopropyl)methoxy]-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-[[1-(trifluoromethyl)cyclopropyl]methoxy]pyrimidin-5-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(trifluoromethoxy)phenyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(1-morpholinocyclopropyl)phenyl]azetidin-1-yl]methanone; 6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(1,1-difluoroethyl)phenyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-fluoro-4-(trifluoromethoxy)phenyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(2,2,2-trifluoroethyl)phenyl]azetidin-1-yl]methanone; [3-(4-cyclopropyl-2-fluoro-phenyl)azetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 5-[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]-2-(trifluoromethoxy)benzonitrile; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-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-triazol-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)azetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(2-chloro-4-fluoro-phenoxy)-2-azaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]oxy]-5-(trifluoromethoxy)benzonitrile; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[2-fluoro-4-(pentafluoro-lambda ６ -sulfanyl)phenyl]methoxy]azetidin-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((6-(trifluoromethyl)pyrazin-2-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]azetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[2-(trifluoromethyl)pyrimidin-4-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((6-(difluoromethoxy)pyridin-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[6-(trifluoromethyl)pyrimidin-4-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[4-(trifluoromethyl)pyrimidin-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((6-methoxypyridin-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((2-(trifluoromethyl)pyrimidin-5-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((5-fluoropyridin-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (4-(5-(tert-butyl)-1,2,4-oxadiazol-3-yl)phenyl)(6-(4-cyclopropyl-1H-imidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]oxy]-1-methyl-pyridin-2-one; [6-(5-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]azetidin-1-yl]-[6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[5-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-(trifluoromethoxy)benzyl)oxy)azetidin-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-(trifluoromethyl)benzyl)oxy)azetidin-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((2-fluoro-5-(trifluoromethyl)benzyl)oxy)azetidin-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((3-fluoro-4-(trifluoromethyl)benzyl)oxy)azetidin-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((2-fluoro-4-(trifluoromethoxy)benzyl)oxy)azetidin-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((3-fluoro-5-(trifluoromethyl)benzyl)oxy)azetidin-1-yl)methanone; (3-((2-chloro-4-fluorobenzyl)oxy)azetidin-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-fluoro-2-(trifluoromethyl)benzyl)oxy)azetidin-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((6-(trifluoromethyl)pyridin-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(6-((5-(trifluoromethyl)pyridin-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-((5-chloropyridin-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-((6-chloropyridin-3-yl)oxy)-2-azaspiro[3.3]heptan-2-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [3-[2-chloro-4-(trifluoromethoxy)phenyl]azetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3,5-difluoro-4-(trifluoromethoxy)phenyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-fluoro-4-(trifluoromethoxy)phenyl]azetidin-1-yl]methanone; [3-(2-tert-butylthiazol-4-yl)azetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[4-[5-(2,2-dimethylpropyl)-1,2,4-oxadiazol-3-yl]phenyl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(3-cyclobutyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aR,6aS)-5-(2-chloro-4-fluoro-phenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-[4-(difluoromethoxy)phenyl]ethynyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aR,6aS)-5-(2-chloro-4-fluoro-phenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone; (3-(2-chloro-3-cyclopropylphenoxy)azetidin-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (3-(4-chloro-3-cyclopropylphenoxy)azetidin-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(2-fluoro-4-(trifluoromethyl)phenoxy)azetidin-1-yl)methanone; (3-(2-chloro-4-methylphenoxy)azetidin-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(2,4-dichlorophenoxy)azetidin-1-yl)methanone; (3-(4-chloro-2-fluorophenoxy)azetidin-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (3-((2-chloro-6-methylpyridin-3-yl)oxy)azetidin-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[3-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[4-(pentafluoro-λ ６ -sulfanyl)phenyl]methoxy]azetidin-1-yl]methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[2-fluoro-4-(pentafluoro-lambda ６ -sulfanyl)phenyl]methoxy]azetidin-1-yl]methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[4-methyl-3-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-[2-(difluoromethyl)phenyl]ethynyl]azetidin-1-yl]methanone; [3-[(4-chloro-2-fluoro-phenyl)methoxy]azetidin-1-yl]-[6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[(2-chloro-4-fluoro-phenyl)methoxy]azetidin-1-yl]-[6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[(2,4-difluorophenyl)methoxy]azetidin-1-yl]methanone; 4-[[2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]oxy]-3-fluoro-benzonitrile; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-[4-(difluoromethoxy)-2-fluoro-phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; 2-[[rac-(3aS,6aR)-2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-yl]oxy]-5-(trifluoromethyl)benzonitrile; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; 5-[[rac-(3aS,6aR)-2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-yl]oxy]-2-(trifluoromethyl)benzonitrile; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-2-methoxy-phenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-2-methylsulfonyl-phenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-3-methyl-phenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-3-chloro-phenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone; 2-fluoro-5-[[rac-(3aS,6aR)-2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-yl]oxy]benzonitrile; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4,5-difluoro-2-methyl-phenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone; 5-fluoro-2-[[rac-(3aS,6aR)-2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-yl]oxy]benzonitrile; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-3-methylsulfonyl-phenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(4-fluoro-3-methoxy-phenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]pyrrol-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[5-(trifluoromethyl)-3-pyridyl]methoxy]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-methyl-3-[[4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-[2-(difluoromethyl)phenyl]ethynyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-methyl-6-[(1-methylcyclopropyl)methoxy]-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-methyl-6-[(1-methylcyclopropyl)methoxy]-3-pyridyl]methanone; [6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(2,2,2-trifluoroethoxy)pyrazol-1-yl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]azetidin-1-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(4-methylpyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(4-methylpyrazol-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-oxadiazol-3-yl)phenyl]-[6-(3-methylpyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[8-[[1-(trifluoromethyl)cyclopropyl]methoxy]-5-azaspiro[2.5]octan-5-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3,3-difluoro-4-[[1-(trifluoromethyl)cyclopropyl]methoxy]-1-piperidyl]methanone; [6-(3-cyclopropylpyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-methyl-6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-3-pyridyl]methanone; [6-(3-cyclopropylpyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-methyl-6-(2,2,2-trifluoro-1,1-dimethyl-ethoxy)-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-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-oxadiazol-3-yl)phenyl]-[6-(3-ethyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(4-ethylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-[4-(trifluoromethyl)imidazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(4-chloroimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 1-[2-[4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)benzoyl]-2-azaspiro[3.3]heptan-6-yl]imidazole-4-carbonitrile; [6-(3-cyclopropyl-1,2,4-triazol-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-oxadiazol-3-yl)-1-bicyclo[1.1.1]pentanyl]-[6-(4-cyclopropylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-1-bicyclo[1.1.1]pentanyl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[1-[1-(trifluoromethyl)cyclopropyl]triazol-4-yl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(2,2,2-trifluoroethoxy)pyrazol-1-yl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-5-yl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[1-[3-(trifluoromethyl)oxetan-3-yl]triazol-4-yl]azetidin-1-yl]methanone; [4-(5-tert-butyl-1,3,4-oxadiazol-2-yl)phenyl]-[6-(3-chloro-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,3,4-oxadiazol-2-yl)phenyl]-[6-(3-cyclopropylpyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(1-tert-butylpyrazol-4-yl)phenyl]-[6-(3-chloro-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(3-cyclopropylpyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-3-yl)phenyl]-[6-(3-chloro-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[1-(trifluoromethyl)cyclopropyl]methoxymethyl]cyclobutyl]methanone; [6-(3-cyclopropylpyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[5-methyl-6-(2,2,2-trifluoro-1,1-dimethyl-ethoxy)-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-dimethyl-ethoxy)-3-pyridyl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[1-(trifluoromethyl)cyclopropyl]methoxy]cyclobutyl]methanone; (6-(3-(azetidin-1-yl)-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-(trifluoromethyl)benzyl)oxy)azetidin-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-4-yl)-2-azaspiro[3.3]heptan-2-yl]-[rac-(3aS,6aR)-5-(2-chloro-4-fluoro-phenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone; [4-(5-tert-butyl-1,2,4-oxadiazol-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-oxadiazol-3-yl)phenyl]-[6-(5-cyclopropylpyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-(1-tert-butylpyrazol-4-yl)azetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-methyl-4-(trifluoromethoxy)phenyl]azetidin-1-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-cyclopropylphenoxy)azetidin-1-yl)methanone; [6-(3-cyclobutyl-1,2,4-triazol-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-cyclopropylpyridin-2-yl)oxy)azetidin-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(3-cyclopropyl-4-(trifluoromethyl)phenoxy)azetidin-1-yl)methanone; 5-cyclopropyl-2-((1-(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl)azetidin-3-yl)oxy)benzonitrile; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-cyclopropyl-2-fluorophenoxy)azetidin-1-yl)methanone; 2-cyclopropyl-6-((1-(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl)azetidin-3-yl)oxy)benzonitrile; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; Methyl 3-[3-[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]oxyphenyl]-2,2-dimethylpropanoate; N-[2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]-3-(trifluoromethyl)benzenesulfonamide; [6-(3-cyclopropyl-1,2,4-triazol-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-oxadiazol-5-yl)-(4-fluorophenyl)methyl]-1-piperidyl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(3-cyclopropyl-2-fluorophenoxy)azetidin-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-(trifluoromethyl)phenoxy)azetidin-1-yl)methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(3-isopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-cyclopropyl-3-fluoropyridin-2-yl)oxy)azetidin-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]-3-pyridyl]azetidin-1-yl]methanone; (4-((3-cyclopropyl-1,2,4-oxadiazol-5-yl)(4-fluorophenyl)methyl)piperidin-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((6-cyclopropyl-2-fluoropyridin-3-yl)oxy)azetidin-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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]azetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[3-hydroxy-3-(trifluoromethyl)pyrrolizino]-3-pyridyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(3R)-3-hydroxy-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidin-1-yl]methanone; N-[2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2-azaspiro[3.3]heptane-6-yl]-2,2-dimethyl-propane-1-sulfonamide; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(3S)-3-hydroxy-3-(trifluoromethyl)pyrrolizino]-3-pyridyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-methylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(2-methoxy-3-(trifluoromethyl)phenoxy)azetidin-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(3-cyclopropyl-4-fluorophenoxy)azetidin-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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)azetidin-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-oxadiazol-5-yl)-(4-fluorophenyl)methyl]-1-piperidyl]-[6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; 2-[[2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methyl]benzoic acid methyl ester; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-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-triazol-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-triazol-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-cyclopropylpyridin-3-yl)oxy)azetidin-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-(4-fluoro-2-mesyl-phenoxy)-2-azaspiro[3.5]nonan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzonitrile; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(2-fluoro-4-methylphenoxy)azetidin-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]methyl]-3-(trifluoromethyl)benzenesulfonamide; 6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-N-[[1-(trifluoromethyl)cyclopropyl]methyl]-2,6-diazaspiro[3.3]heptane-2-sulfonamide; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((6-(trifluoromethyl)pyridazin-3-yl)oxy)azetidin-1-yl)methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(4-((1,1,1-trifluoropropan-2-yl)oxy)-1H-pyrazol-1-yl)azetidin-1-yl)methanone; (2-Benzofurazan-4-ylsulfonyl-2,6-diazaspiro[3.3]heptan-6-yl)-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-[1-(2H-tetrazol-5-yl)cyclopropyl]phenyl]azetidin-1-yl]methanone; N-[[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-4-piperidyl]methyl]-4-(trifluoromethyl)benzenesulfonamide; (3-((6-chloro-5-cyclopropylpyridin-3-yl)oxy)azetidin-1-yl)(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-N-(4-fluorobenzyl)-2,6-diazaspiro[3.3]heptane-2-sulfonamide; 2-[[2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methyl]benzenesulfonamide; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-4-piperidyl]methyl]-4-(trifluoromethoxy)benzenesulfonamide; 6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-N-[1-(trifluoromethyl)cyclopropyl]-2,6-diazaspiro[3.3]heptane-2-sulfonamide; 4-(1-(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl)azetidin-3-yl)-1-(2,2,2-trifluoroethyl)pyridin-2(1H)-one; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[2-fluoro-4-(trifluoromethyl)benzyl]amino]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzoic acid methyl ester; (2-benzylsulfonyl-2,6-diazaspiro[3.3]heptan-6-yl)-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-(2-fluoro-4-mesyl-benzyl)oxyazetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[6-(trifluoromethyl)pyridazin-3-yl]amino]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-N-(1-methylcyclopropyl)-2,6-diazaspiro[3.3]heptane-2-sulfonamide; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((6-(trifluoromethyl)pyridin-3-yl)oxy)azetidin-1-yl)methanone; 4-chloro-N-[[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-4-piperidyl]methyl]benzenesulfonamide; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((2-cyclopropylpyrimidin-4-yl)oxy)azetidin-1-yl)methanone; (6-(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)(4-fluoro-2-(trifluoromethyl)phenyl)methanone; N-[[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]methyl]-4-(trifluoromethyl)benzenesulfonamide; N-[2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 2-[3-[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]oxyphenyl]-2-methylpropanoic acid; [3-(6-cyclopropylpyridazin-3-yl)oxyazetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(3,5-dimethylisoxazol-4-yl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((2-(trifluoromethyl)pyrimidin-4-yl)oxy)azetidin-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((6-(trifluoromethyl)pyrimidin-4-yl)oxy)azetidin-1-yl)methanone; [2-[(6-chloro-2-pyridyl)sulfonyl]-2,6-diazaspiro[3.3]heptan-6-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 3-[[6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzonitrile; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-(5-(2,4-difluorophenyl)-4H-1,2,4-triazol-3-yl)azetidin-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(4-fluoro-2-methoxy-phenyl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; (2S)-2-[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)methanone; 4-[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]benzenesulfonamide; 3-[[6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]-4-fluoro-benzamide; N-[4-[[6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzamide; 3-[3-[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]oxyphenyl]-2,2-dimethylpropanoic acid; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(5-methylisoxazol-4-yl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; (2R)-2-[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-4-piperidyl]-2-(4-fluorophenyl)acetamide; N-[[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]methyl]-4-fluoro-2-(trifluoromethyl)benzenesulfonamide; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((6-(trifluoromethyl)pyrazin-2-yl)oxy)azetidin-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-(2-triflyl-2,6-diazaspiro[3.3]heptan-6-yl)methanone; 2-[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-4-piperidyl]-2-(4-fluorophenyl)acetamide; (2S)-2-[4-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]piperazino]-2-(4-fluorophenyl)acetamide; [3-[[4-(pentafluoro-λ 6-sulfanyl)phenyl]methoxy]azetidin-1-yl]-[6-[4-(trifluoromethyl)imidazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; 4-[[6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzonitrile; [6-(3-cyclopropyl-1,2,4-triazol-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-aminopyrimidin-5-yl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; 2-[2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]-N-methyl-2-phenyl-acetamide; 1-(1-(6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl)azetidin-3-yl)-N-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carboxamide; 2-[[2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methyl]benzoic acid; 6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-N,N-dimethyl-2,6-diazaspiro[3.3]heptane-2-sulfonamide; [6-(4-methylimidazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[4-(pentafluoro-λ 6-sulfanyl)phenyl]methoxy]azetidin-1-yl]methanone; (6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)(3-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)azetidin-1-yl)methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-4-piperidyl]methyl]-4-fluoro-benzenesulfonamide; [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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-4-piperidyl]-4-(trifluoromethyl)benzenesulfonamide; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(trifluoromethyl)pyridazin-3-yl]oxyazetidin-1-yl]methanone; 2-[[6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzamide; 4-[[6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzoic acid; N-[[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-4-piperidyl]methyl]benzenesulfonamide; (2R)-2-[4-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]piperazino]-2-(4-fluorophenyl)acetamide; 3-[[6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]-4-fluoro-benzoic acid; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-(5-ethyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]piperazino]-2-(4-fluorophenyl)-N-methyl-acetamide; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[2-(1-methylpyrazol-4-yl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; 2-[4-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-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)azetidin-1-yl)methanone; 2-[[6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]-N-methyl-benzamide; (2R)-2-[4-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]piperazino]-2-(4-fluorophenyl)-N-methyl-acetamide; N-[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-4-piperidyl]-4-fluoro-benzenesulfonamide; 1-[2-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]-2,2,2-trifluoro-ethanone; 2-[[6-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-2-yl]sulfonyl]benzoic acid; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]piperazino]-2-(4-fluorophenyl)-N-methyl-acetamide; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[6-(triazol-2-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[6-(triazol-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]azetidin-1-yl]-[6-[2-(trifluoromethyl)pyrimidin-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)triazol-4-yl]phenyl]azetidin-1-yl]-[6-(5-fluoro-3-pyridyl)-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[6-(5-fluoro-3-pyridyl)-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-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-triazol-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-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-(5-cyclopropyl-3-methyl-pyrazol-1-yl)-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-(5-cyclopropyl-3-methyl-pyrazol-1-yl)-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-(3,5-dimethylpyrazol-1-yl)-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(1H-pyrazolo[4,3-b]pyridin-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-triazol-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-triazol-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-triazol-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-triazol-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-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; 5-[[2-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]-2-(trifluoromethyl)benzonitrile; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; 4-[[2-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]-2-(trifluoromethyl)benzonitrile; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]-5-(trifluoromethyl)benzonitrile; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-3-pyridyl]azetidin-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(3R)-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidin-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[[6-(trifluoromethyl)-3-pyridyl]methyl]-1-bicyclo[1.1.1]pentanyl]azetidin-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]pyridin-5-ylmethyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[(5-cyclopropyl-4H-1,2,4-triazol-3-yl)methyl]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-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-methylsulfonyl-phenyl)-3-pyridyl]azetidin-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-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carbonyl]-2-azaspiro[3.4]octan-6-yl]oxy]-2-(trifluoromethyl)pyridine-4-carbonitrile; [6-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3.4]octan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-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-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[[2-methoxy-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[4-[5-[(1-methylcyclopropyl)methyl]-4H-1,2,4-triazol-3-yl]phenyl]azetidin-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[[1-(trifluoromethyl)cyclopropyl]methylamino]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(3S)-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidin-1-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[[4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidin-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptane-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-triazol-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-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-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-triazol-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-triazol-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-triazol-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-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(trifluoromethyl)pyrimidin-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-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]azetidin-1-yl]-[6-(1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[(4-dimethylphosphorylphenyl)methoxy]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[(4-dimethylphosphorylphenyl)methoxy]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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)triazol-4-yl]phenyl]azetidin-1-yl]-[6-(1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-[5-[1-(trifluoromethyl)cyclopropyl]-4H-1,2,4-triazol-3-yl]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[5-[1-(trifluoromethyl)cyclopropyl]-4H-1,2,4-triazol-3-yl]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]methanone; [3-[3-[[[1-(trifluoromethyl)cyclopropyl]amino]methyl]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-[[1-(trifluoromethyl)cyclopropyl]methylamino]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-[3-(trifluoromethyl)azetidin-1-yl]-3-pyridyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[2-[3-(trifluoromethyl)azetidin-1-yl]pyrimidin-5-yl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-3-pyridyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[4-[5-[(1-methylcyclopropyl)methyl]-4H-1,2,4-triazol-3-yl]phenyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-[(3S)-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-[(3R)-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-[(1,1-dioxothietan-3-yl)methylamino]-3-pyridyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; 2-[4-[1-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]phenyl]benzamide; [6-[[4-(methylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-(5-cyclopropyl-4H-1,2,4-triazol-3-yl)-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]methanone; [3-[3-(5-cyclopropyl-4H-1,2,4-triazol-3-yl)-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]methanone; [3-[3-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2,7-diazaspiro[3.4]octan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[6-(trifluoromethyl)pyridazin-3-yl]methyl]-2,7-diazaspiro[3.4]octan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-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-triazol-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-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[[[1-(trifluoromethyl)cyclopropyl]amino]methyl]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[3-[[1-(trifluoromethyl)cyclopropyl]methylamino]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-[5-[(1-methylcyclopropyl)methyl]-4H-1,2,4-triazol-3-yl]phenyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(5-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[[2-methoxy-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]-3-pyridyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-(3-hydroxy-3-methyl-azetidin-1-yl)-3-pyridyl]azetidin-1-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; 3-(trifluoromethyl)-N-[2-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-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-triazol-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-triazol-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-triazol-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-triazol-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-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-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-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[[3-(trifluoromethyl)oxetan-3-yl]amino]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-[5-[1-(trifluoromethyl)cyclopropyl]-4H-1,2,4-triazol-3-yl]phenyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[4-(5-cyclopropyl-1H-1,2,4-triazol-3-yl)phenyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(3-fluoro-5-methylsulfonyl-phenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[5-[[1-(trifluoromethyl)cyclopropyl]methylamino]pyrazin-2-yl]azetidin-1-yl]methanone; [3-[4-(5-cyclobutyl-1H-1,2,4-triazol-3-yl)phenyl]azetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-fluoro-2-methylsulfonyl-phenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(3S)-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[[1-(trifluoromethyl)cyclopropyl]amino]-3-pyridyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[5-[[1-(trifluoromethyl)cyclopropyl]methylamino]-2-pyridyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-[3-(trifluoromethyl)azetidin-1-yl]pyrimidin-5-yl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(3S)-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-[(3S)-3-(trifluoromethyl)pyrrolidin-1-yl]pyrimidin-5-yl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-[(3R)-3-(trifluoromethyl)pyrrolidin-1-yl]pyrimidin-5-yl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(2-fluoro-4-methylsulfonyl-phenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-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-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[[1-(trifluoromethyl)cyclopropyl]amino]-3-pyridyl]azetidin-1-yl]methanone; (2R)-1-[4-[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]phenyl]-4,4-difluoro-piperidine-2-carboxamide; (2R)-1-[4-[1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]phenyl]-4,4-difluoro-piperidine-2-carboxamide; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-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-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[3-(trifluoromethyl)azetidin-1-yl]-3-pyridyl]azetidin-1-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[3-(trifluoromethylsulfonyl)phenyl]methoxy]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[[4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-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-triazol-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-triazol-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-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]azetidin-3-yl]phenyl]-4,4-difluoro-piperidine-2-carboxamide; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-(3-hydroxy-3-methyl-azetidin-1-yl)-3-pyridyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[6-[(1,1-dioxothiolan-3-yl)amino]-3-pyridyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[4-(3-fluorophenoxy)-1-piperidyl]methanone; [3-(4-cyclobutylphenyl)azetidin-1-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[2-(2-fluoro-6-methyl-phenyl)ethyl]azetidin-1-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[3-[(E)-2-(3-fluorophenyl)vinyl]azetidin-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]azetidin-1-yl]-[6-(5-fluoro-3-pyridyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[(2-chloro-4-fluoro-phenyl)methoxy]azetidin-1-yl]-[6-(5-fluoro-3-pyridyl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[[2-chloro-4-(trifluoromethyl)phenyl]methylamino]azetidin-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]azetidin-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(trifluoromethyl)pyrazin-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]azetidin-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)azetidin-1-yl]-3-pyridyl]azetidin-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]azetidin-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[3-cyclopropyl-4-(trifluoromethyl)phenoxy]azetidin-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]azetidin-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-fluoro-phenyl)methoxy]azetidin-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-(4-isopropyl-N-methyl-anilino)-3-pyridyl]azetidin-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]heptane-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]benzonitrile; [3-[5-(2,4-dichlorophenyl)-2-pyridyl]azetidin-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[6-(2-chloro-4-methylsulfonyl-phenyl)-3-pyridyl]azetidin-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone; and [3-[5-(4-chloro-2-fluoro-phenyl)-2-pyridyl]azetidin-1-yl]-[6-[6-(trifluoromethyl)-3-pyridyl]-2-azaspiro[3.3]heptan-2-yl]methanone Selected from:

2. A compound of formula (I) according to claim 1, or a pharma- ceutically acceptable salt thereof.

16. 3. A compound of formula (I) or a pharma- ceutically acceptable salt thereof as defined in claim 1 or 2 for use as a therapeutically active substance.

17. A pharmaceutical composition comprising a compound of formula (I) according to claim 1 or 2 or a pharma- ceutically acceptable salt thereof and a therapeutically inert carrier.

18. 18. A pharmaceutical composition according to claim 17 for use in the treatment or prevention of neuroinflammation, neurodegenerative diseases, pain, cancer, psychiatric disorders and / or inflammatory bowel disease in a mammal.

19. 19. The pharmaceutical composition of claim 18, wherein the neuroinflammation, neurodegenerative disease, pain, cancer and psychiatric disorder is 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, spasticity associated with pain, abdominal pain, abdominal pain associated with irritable bowel syndrome, and / or visceral pain.

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