Heterocyclic compounds as inhibitors of monoacylglycerol lipase (MAGL)

Abstract

The present invention relates to novel heterocyclic compounds having the general formula (I): TIFF2025536386000233.tif29170 (Wherein A, B, L, W, Y, Z and R 1 ~R 3 as described herein), compositions comprising the compounds, methods of making the compounds, and methods of using the compounds are provided.

Description

[Technical Field]

[0001] 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] 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; 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 are 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 dramatically reduced 2-AG hydrolase activity and dramatically elevated 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 regulating 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 shown to suppress glial cell activation and disease progression in preclinical models, including Alzheimer's disease and multiple sclerosis (Lleo A., Cell Mol Life Sci. 2007, 64, 1403). Importantly, genetic and / or pharmacological disruption of MAGL activity also inhibits LPS-induced microglial activation 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, reduced 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 the natural MAGL substrate, 2-AG, 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), myelinating cells in the central nervous system, and their precursors (OPCs) 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] In recent years, metabolism, particularly lipid metabolism, has become increasingly important in cancer research. Researchers believe that de novo fatty acid synthesis plays an important role in tumor development. Many studies have demonstrated that endocannabinoids have antitumorigenic effects, including antiproliferative, apoptotic, and antimetastatic effects. MAGL, 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 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).

[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 neuroprotection and myelin regeneration. Thus, there is a high unmet medical need for new MAGL inhibitors. Summary of the Invention

[0011] In a first aspect, the present invention provides a compound of formula (I) [ka] (Wherein A, B, L, W, Y, Z and R 1 ~R 3 is as described herein).

[0012] In further aspects, the present invention provides compositions comprising compounds of formula (I), methods of making compounds of formula (I), and methods of using compounds of formula (I). DETAILED DESCRIPTION OF THE INVENTION

[0013] 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 herein (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 one or any novel combination of features disclosed herein (including any accompanying claims, abstract, and drawings), or any novel one or any novel combination of steps of any method or process so disclosed.

[0014] The term "alkyl" refers to alkyl groups containing 1 to 6 carbon atoms ("C 1-6"-alkyl") refers to a monovalent or polyvalent, e.g., monovalent or divalent, straight-chain or branched saturated hydrocarbon group, e.g., of 1, 2, 3, 4, 5, or 6 carbon atoms. In some embodiments, an alkyl group contains 1 to 4 carbon atoms, e.g., 1, 2, 3, or 4 carbon atoms. In other embodiments, an alkoxy group contains 1 to 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.

[0015] The term "alkoxy" refers to an alkyl group, as defined previously, attached to the parent molecular moiety through an oxygen atom. Unless otherwise specified, an alkoxy group contains 1 to 6 carbon atoms ("C 1-6 -alkoxy"). In some embodiments, the alkoxy group contains 1 to 4 carbon atoms, e.g., 1, 2, 3, or 4 carbon atoms. In other embodiments, the alkoxy group contains 1 to 3 carbon atoms. Some non-limiting examples of alkoxy groups include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, and tert-butoxy. A particularly preferred, but non-limiting example of alkoxy is methoxy.

[0016] The term "cycloalkylalkyl" refers to a cycloalkyl group, as defined above, attached to the parent molecular moiety through an alkyl group. A particularly preferred, but non-limiting example of a cycloalkylalkyl is cyclopropylmethyl.

[0017] 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).

[0018] As used herein, the term "cycloalkyl" refers to a saturated monocyclic or bicyclic hydrocarbon group of 3 to 10 ring carbon atoms ("C 3-10 In some preferred embodiments, the cycloalkyl group is a monocyclic hydrocarbon group of 3 to 8 ring carbon atoms. "Bicyclic cycloalkyl" refers to cycloalkyl moieties consisting of two saturated carbocyclic rings that share two 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 spirocyclic moieties (i.e., the two rings are connected through one common ring atom). Preferably, the cycloalkyl group is a 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.

[0019] The term "aryl" refers to a group having a total of 6 to 14 ring members ("C6-C 14 -aryl"), 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.

[0020] The term "hydroxy" refers to the group --OH.

[0021] The term "cyano" refers to a -CN (nitrile) group.

[0022] The term "sulfamoyl" refers to the group H2N-SO2-.

[0023] The term "haloalkyl" refers to an alkyl group, as defined herein, in which at least one of the alkyl group's hydrogen atoms is replaced with a halogen atom, preferably fluoro. Preferably, "haloalkyl" refers to an alkyl group in which one, two, or three of the alkyl group's hydrogen atoms are replaced with a halogen atom, 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.

[0024] The term "halocycloalkyl" refers to a cycloalkyl group, as defined herein, in which at least one of the cycloalkyl group's hydrogen atoms has been replaced with a halogen atom, preferably fluoro. Preferably, "halocycloalkyl" refers to a cycloalkyl group in which one, two, or three of the cycloalkyl group's hydrogen atoms have been replaced with a halogen atom, most preferably fluoro. Particularly preferred, but non-limiting, examples of halocycloalkyl are 1-fluorocyclopropyl and 2,2-difluorocyclopropyl.

[0025] The term "hydroxycycloalkyl" refers to a cycloalkyl group, as defined herein, in which at least one of the hydrogen atoms of the cycloalkyl group has been replaced with a hydroxy group. Preferably, "hydroxycycloalkyl" refers to a cycloalkyl group in which one, two, or three hydrogen atoms of the cycloalkyl group have been replaced with a hydroxy group. A particularly preferred, but non-limiting, example of a hydroxycycloalkyl is 1-hydroxycyclopropyl.

[0026] The term "haloalkylcycloalkyl" refers to a cycloalkyl group, as defined herein, in which at least one of the cycloalkyl group's hydrogen atoms has been replaced with a haloalkyl group. In some embodiments, "haloalkylcycloalkyl" refers to a cycloalkyl group in which one, two, or three hydrogen atoms of the cycloalkyl group have been replaced with a haloalkyl group. Preferably, "haloalkylcycloalkyl" refers to a cycloalkyl group in which one to two hydrogen atoms of the cycloalkyl group have been replaced with a haloalkyl group. Particularly preferred, but non-limiting, examples of haloalkylcycloalkyl are 1-(trifluoromethyl)cyclopropyl and 2-(trifluoromethyl)cyclopropyl.

[0027] The term "haloalkoxy" refers to an alkoxy group, as defined herein, in which at least one hydrogen atom of the alkoxy group is replaced by a halogen atom, preferably fluoro. Preferably, "haloalkoxy" refers to an alkoxy group in which one, two, or three hydrogen atoms of the alkoxy group are replaced by 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.

[0028] 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, and phosphoric acid (especially hydrochloric acid), and 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, and N-acetylcysteine. Additionally, 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, and magnesium salts. 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.

[0029] 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.

[0030] According to the Cahn-Ingold-Prelog rules, the asymmetric carbon atom can be of the "R" or "S" configuration.

[0031] The abbreviation "MAGL" refers to the enzyme monoacylglycerol lipase. The terms "MAGL" and "monoacylglycerol lipase" are used interchangeably herein.

[0032] The term "treatment" as used herein includes (1) suppressing a condition, disorder, or symptom (e.g., arresting, reducing, or delaying the onset of a disease or, in the case of maintenance treatment, the recurrence of a disease, the onset of at least one clinical or subclinical symptom of a disease); and / or (2) alleviating symptoms (i.e., causing regression of a condition, disorder, or symptom, or at least one of its clinical or subclinical symptoms). The benefit to the patient to be treated is either statistically significant or at least perceptible to the patient or physician. However, it will be understood that when a pharmaceutical agent is administered to a patient to treat a disease, the result may not necessarily be effective treatment.

[0033] The term "prophylaxis" as used herein includes preventing or delaying the appearance of clinical symptoms of a condition, disorder or condition in a mammal, particularly a human, who may be affected by or predisposed to the condition, disorder or condition, but who has not yet experienced or exhibited clinical or subclinical symptoms of the condition, disorder or condition.

[0034] 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 central nervous system injury, for example, as a result of traumatic brain injury (TBI).

[0035] The term "traumatic brain injury" (also known as "TBI," "intracranial injury") relates to damage to the brain resulting from an external mechanical force such as rapid acceleration or deceleration, impact, blast wave, or penetration by a projectile.

[0036] 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.

[0037] 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.

[0038] 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.

[0039] 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, drug 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.

[0040] The term "cancer" refers to a disease 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.

[0041] 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.

[0042] Compounds of the Invention In a first aspect, the present invention provides a compound of formula (I) [ka] or a pharmaceutically acceptable salt thereof, W and Z are each independently selected from CH2 and CH2CH2; Y is selected from CH and N; U is selected from CH and N; V is selected from NH, O and S; X is selected from NH and O; L is selected from CH2 and O; A is selected from the following: [ka] B is selected from the following: [ka] and 9-membered fused bicyclic heteroaryl containing 1 to 3 heteroatoms selected from N, O, and S, with the remaining ring atoms being carbon; R 1is hydrogen, halogen, cyano, C1-C6-alkyl, C1-C6-alkoxy, haloC1-C6-alkyl, halo-C1-C6-alkoxy, C3-C 10 -Cycloalkyl, halo-C3-C 10 -Cycloalkyl, C3-C 10 -Cycloalkyl-C1-C6-alkyl, halo-C1-C6-alkyl-C3-C 10 -Cycloalkyl, C6-C 14 -aryl, sulfamoyl, group [ka] and (C1-C6-alkyl)2PO-; R 1a is selected from C1-C6-alkyl and halo-C1-C6-alkyl; R 2 is selected from hydrogen, halogen, cyano, C-C-alkyl, C-C-alkoxy, halo-C-C-alkyl, and halo-C-C-alkoxy; and R 3 is C3-C 10 -Cycloalkyl, hydroxy-C3-C 10 -Cycloalkyl, amino-C3-C 10 -Cycloalkyl, halo-C3-C 10 -selected from cycloalkyl, C1-C6-alkyl, halo-C1-C6-alkyl, C1-C6-alkoxy and halo-C1-C6-alkoxy, The present invention provides a compound, or a pharmaceutically acceptable salt thereof.

[0043] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: W and Z are each independently selected from CH2 and CH2CH2; Y is selected from CH and N; U is selected from CH and N; V is selected from NH, O and S; L is selected from CH2 and O; A is selected from: [ka] B is selected from the following: [ka] R 1 is hydrogen, halogen, cyano, C1-C6-alkyl, C1-C6-alkoxy, halo-C1-C6-alkyl, halo-C1-C6-alkoxy, C3-C 10 -Cycloalkyl, halo-C3-C 10 -Cycloalkyl, C3-C 10 -Cycloalkyl-C1-C6-alkyl, halo-C1-C6-alkyl-C3-C 10 -Cycloalkyl, C6-C 14 -selected from aryl, sulfamoyl, and (C1-C6-alkyl)2PO-; R 2 is selected from hydrogen, halogen, cyano, C-C-alkyl, C-C-alkoxy, halo-C-C-alkyl, and halo-C-C-alkoxy; and R 3 But C3-C 10 -Cycloalkyl, hydroxy-C3-C 10 -Cycloalkyl, halo-C3-C 10 -selected from cycloalkyl, C1-C6-alkyl, halo-C1-C6-alkyl, C1-C6-alkoxy and halo-C1-C6-alkoxy, The present invention provides a compound, or a pharmaceutically acceptable salt thereof.

[0044] In a preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein W and Z are both CH2.

[0045] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein W and Z are both CH2CH2.

[0046] In a preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein Y is CH.

[0047] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein Y is N.

[0048] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, W and Z are both CH2; or W and Z are both CH2CH2; and Y is selected from CH and N; The present invention provides a compound, or a pharmaceutically acceptable salt thereof.

[0049] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, W and Z are both CH2; and The present invention provides a compound, or a pharmaceutically acceptable salt thereof, wherein Y is CH.

[0050] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is [ka] The present invention provides a compound selected from:

[0051] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is [ka] The present invention provides a compound selected from:

[0052] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is [ka] The present invention provides a compound selected from:

[0053] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is [ka] The present invention provides a compound selected from:

[0054] In a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is [ka] The present invention provides a compound selected from:

[0055] In a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is [ka] The present invention provides a compound selected from:

[0056] In a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is [ka] is.

[0057] In a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is [ka] is.

[0058] In a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is [ka] is.

[0059] In a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein L is CH2.

[0060] In a preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein A is [ka] is selected from.

[0061] 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 [ka] is.

[0062] 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 [ka] is.

[0063] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: R 1 is hydrogen, cyano, C1-C6-alkyl, halo-C1-C6-alkyl, C3-C 10 -Cycloalkyl, C3-C 10 -Cycloalkyl-C1-C6-alkyl, halo-C1-C6-alkyl-C3-C 10 -Cycloalkyl, C6-C 14 -aryl, sulfamoyl, group [ka] and (C1-C6-alkyl)2PO-; R 1a is selected from C1-C6-alkyl and halo-C1-C6-alkyl; and X is selected from NH and O; The present invention provides a compound, or a pharmaceutically acceptable salt thereof.

[0064] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: R 1 is selected from hydrogen, methyl, ethyl, tert-butyl, cyano, CHF2, CF3, 1,1-difluoroethyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, sulfamoyl, dimethylphosphoryl, phenyl, and (CF3)cyclopropyl; R 1ais selected from methyl and CF3; and X is selected from NH and O; The present invention provides a compound, or a pharmaceutically acceptable salt thereof.

[0065] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, R 1 halo-C1-C6-alkyl, C3-C 10 -cycloalkyl, halo-C1-C6-alkyl-C3-C 10 -cycloalkyl, and groups [ka] Selected from; R 1a is halo-C1-C6-alkyl; and X is selected from NH and O; The present invention provides a compound, or a pharmaceutically acceptable salt thereof.

[0066] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, R 1 are CHF2, CF3, 2,2,2-trifluoroethyl, cyclopropyl, (CF3)cyclopropyl, and the group [ka] Selected from; R 1a is CF3; and X is selected from NH and O; The present invention provides a compound, or a pharmaceutically acceptable salt thereof.

[0067] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, R 1CF3, cyclopropyl, (CF3)cyclopropyl, and groups [ka] Selected from; R 1a is CF3; and X is selected from NH and O; The present invention provides a compound, or a pharmaceutically acceptable salt thereof.

[0068] In one embodiment, the present invention provides a compound comprising R 1 is hydrogen, cyano, C1-C6-alkyl, halo-C1-C6-alkyl, C3-C 10 -Cycloalkyl, C3-C 10 -Cycloalkyl-C1-C6-alkyl, halo-C1-C6-alkyl-C3-C 10 -Cycloalkyl, C6-C 14 -aryl, sulfamoyl, and (C1-C6-alkyl)2PO-, or a pharmaceutically acceptable salt thereof.

[0069] In one embodiment, the present invention provides a compound comprising R 1 is selected from hydrogen, methyl, ethyl, tert-butyl, cyano, CHF, CF, 1,1-difluoroethyl, 2,2,2-trifluoroethyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, sulfamoyl, dimethylphosphoryl, phenyl, and (CF)cyclopropyl, or a pharmaceutically acceptable salt thereof.

[0070] In a preferred embodiment, the present invention provides R 1 halo-C1-C6-alkyl, C3-C 10 -cycloalkyl, and halo-C1-C6-alkyl-C3-C 10 -cycloalkyl, or a pharmaceutically acceptable salt thereof.

[0071] In a preferred embodiment, the present invention provides R 1 is selected from CHF2, CF3, 2,2,2-trifluoroethyl, cyclopropyl, and (CF3)cyclopropyl, or a pharmaceutically acceptable salt thereof.

[0072] In a particularly preferred embodiment, the present invention provides 1 is selected from CF3, cyclopropyl, and 1-(trifluoromethyl)cyclopropyl, or a pharmaceutically acceptable salt thereof.

[0073] In a particularly preferred embodiment, the present invention provides 1 is halo-C1-C6-alkyl, or a pharmaceutically acceptable salt thereof.

[0074] In a particularly preferred embodiment, the present invention provides 1 is CF3, or a pharmaceutically acceptable salt thereof.

[0075] In one embodiment, the present invention provides a compound comprising R 2 is selected from hydrogen, C1-C6 alkyl, and halo-C1-C6 alkyl, or a pharmaceutically acceptable salt thereof.

[0076] In one embodiment, the present invention provides a compound comprising R 2 is selected from hydrogen, methyl, ethyl, and CF3, or a pharmaceutically acceptable salt thereof.

[0077] In a preferred embodiment, the present invention provides R 2 is selected from hydrogen, methyl and CF3, or a pharmaceutically acceptable salt thereof.

[0078] In a particularly preferred embodiment, the present invention provides 2 is hydrogen, or a pharmaceutically acceptable salt thereof.

[0079] In one embodiment, the present invention provides a compound comprising R 3 But C3-C 10 -Cycloalkyl, hydroxy-C3-C 10 -Cycloalkyl, amino-C3-C 10 -cycloalkyl, and halo-C1-C6-alkyl, or a pharmaceutically acceptable salt thereof.

[0080] In one embodiment, the present invention provides a compound comprising R 3 is selected from cyclopropyl, 1-hydroxycyclopropyl, 1-aminocyclopropyl, and CF3, or a pharmaceutically acceptable salt thereof.

[0081] In one embodiment, the present invention provides a compound comprising R 3 But C3-C 10 -Cycloalkyl, hydroxy-C3-C 10 -cycloalkyl, halo-C1-C6-alkyl, or a pharmaceutically acceptable salt thereof.

[0082] In a preferred embodiment, the present invention provides R 3 But C3-C 10 The present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein the aryl group is selected from halo-C1-C6-cycloalkyl and halo-C1-C6-alkyl.

[0083] In a preferred embodiment, the present invention provides R 3 is selected from cyclopropyl, hydroxycyclopropyl, and CF3, or a pharmaceutically acceptable salt thereof.

[0084] In a particularly preferred embodiment, the present invention provides3 is selected from cyclopropyl and CF3, or a pharmaceutically acceptable salt thereof.

[0085] In a preferred embodiment, the present invention provides R 3 But C3-C 10 Provided are compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, which are cycloalkyl.

[0086] In a particularly preferred embodiment, the present invention provides 3 is cyclopropyl, or a pharmaceutically acceptable salt thereof.

[0087] In a particularly preferred embodiment, the present invention provides 3 is CF3, or a pharmaceutically acceptable salt thereof.

[0088] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: W and Z are each independently selected from CH2 and CH2CH2; Y is selected from CH and N; U is selected from CH and N; V is selected from NH, O and S; X is selected from NH and O; L is selected from CH2 and O; A, [ka] Selected from; B is selected from the following: [ka] R 1 is hydrogen, cyano, C1-C6-alkyl, halo-C1-C6-alkyl, C3-C10 -Cycloalkyl, C3-C 10 -Cycloalkyl-C1-C6-alkyl, halo-C1-C6-alkyl-C3-C 10 -Cycloalkyl, C6-C 14 -aryl, sulfamoyl, group [ka] and (C1-C6-alkyl)2PO-; R 1a is selected from C1-C6-alkyl and halo-C1-C6-alkyl; R 2 is selected from hydrogen, C1-C6-alkyl, and halo-C1-C6-alkyl; and R 3 But C3-C 10 -Cycloalkyl, hydroxy-C3-C 10 -Cycloalkyl, amino-C3-C 10 -cycloalkyl, halo-C1-C6-alkyl, or a pharmaceutically acceptable salt thereof.

[0089] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, W and Z are both CH2; or W and Z are both CH2CH2; Y is selected from CH and N; X is selected from NH and O; L is CH; A, [ka] Selected from; B is selected from the following: [ka] R 1halo-C1-C6-alkyl, C3-C 10 -cycloalkyl, halo-C1-C6-alkyl-C3-C 10 -cycloalkyl, and groups [ka] Selected from; R 1a is halo-C1-C6-alkyl; R 2 is selected from hydrogen, C1-C6-alkyl, and halo-C1-C6-alkyl; and R 3 But C3-C 10 -Cycloalkyl, hydroxy-C3-C 10 -cycloalkyl, halo-C1-C6-alkyl, or a pharmaceutically acceptable salt thereof.

[0090] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, W and Z are both CH2; or W and Z are both CH2CH2; Y is selected from CH and N; X is selected from NH and O; L is CH; A, [ka] Selected from; B is selected from the following: [ka] R 1 are CHF2, CF3, 2,2,2-trifluoroethyl, cyclopropyl, (CF3)cyclopropyl, and the group [ka] Selected from; R 1a is CF3; R 2 is selected from hydrogen, methyl, and CF3; and R 3 is selected from cyclopropyl, hydroxycyclopropyl, and CF3, or a pharmaceutically acceptable salt thereof.

[0091] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: W and Z are each independently selected from CH2 and CH2CH2; Y is selected from CH and N; U is selected from CH and N; V is selected from NH, O and S; L is selected from CH2 and O; A, [ka] Selected from; B is selected from the following: [ka] R 1 is hydrogen, cyano, C1-C6-alkyl, halo-C1-C6-alkyl, C3-C 10 -Cycloalkyl, C3-C 10 -Cycloalkyl-C1-C6-alkyl, halo-C1-C6-alkyl-C3-C 10 -Cycloalkyl, C6-C 14 -selected from aryl, sulfamoyl, and (C1-C6-alkyl)2PO-; R 2 is selected from hydrogen, C1-C6-alkyl, and halo-C1-C6-alkyl; and R 3 But C3-C 10-Cycloalkyl, hydroxy-C3-C 10 -cycloalkyl, halo-C1-C6-alkyl, or a pharmaceutically acceptable salt thereof.

[0092] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, W and Z are both CH2; or W and Z are both CH2CH2; Y is selected from CH and N; L is CH; A, [ka] Selected from; B is selected from the following: [ka] R 1 halo-C1-C6-alkyl, C3-C 10 -cycloalkyl, and halo-C1-C6-alkyl-C3-C 10 -cycloalkyl; R 2 is selected from hydrogen, C1-C6-alkyl, and halo-C1-C6-alkyl; and R 3 But C3-C 10 -Cycloalkyl, hydroxy-C3-C 10 -cycloalkyl, halo-C1-C6-alkyl, or a pharmaceutically acceptable salt thereof.

[0093] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, W and Z are both CH2; or W and Z are both CH2CH2; Y is selected from CH and N; L is CH; A, [ka] Selected from; B is selected from the following: [ka] R 1 is selected from CHF2, CF3, 2,2,2-trifluoroethyl, cyclopropyl, and (CF3)cyclopropyl; R 2 is selected from hydrogen, methyl, and CF3; and R 3 is selected from cyclopropyl, hydroxycyclopropyl, and CF3, or a pharmaceutically acceptable salt thereof.

[0094] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is selected from: [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-5-(trifluoromethyl)pyrazol-4-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-[[1-methyl-5-(trifluoromethyl)pyrazol-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-methyl-4-(trifluoromethyl)pyrazol-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-[[5-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1H-pyrazol-5-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)pyrazol-1-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-[[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]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-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1H-1,2,4-triazol-3-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-(trifluoromethyl)-1H-1,2,4-triazol-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-[[5-(trifluoromethyl)-1H-1,2,4-triazol-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-[[4-(trifluoromethyl)pyrazol-1-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-[4-(trifluoromethyl)thiazol-2-yl]oxy-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-[[1-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(trifluoromethyl)-1,2,4-thiadiazol-5-yl]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-(trifluoromethyl)-1,2,4-thiadiazol-5-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-[[3-(trifluoromethyl)-1,2,4-thiadiazol-5-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]-[7-[[3-(trifluoromethyl)isoxazol-5-yl]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-[[2-(trifluoromethyl)thiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(trifluoromethyl)-1,2,4-thiadiazol-3-yl]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-(trifluoromethyl)-1,2,4-thiadiazol-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-[[5-(trifluoromethyl)-1,2,4-thiadiazol-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-[[4-(trifluoromethyl)oxazol-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [7-[[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-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]-[7-[[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]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-[[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [7-[[5-(trifluoromethyl)-1H-pyrazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-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]-[7-[[5-(trifluoromethyl)-1H-pyrazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(difluoromethyl)thiazol-2-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [7-[[5-(difluoromethyl)thiazol-2-yl]methyl]-2,7-diazaspiro[3.5]nonan-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]-[7-[[5-(difluoromethyl)thiazol-2-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [7-[[5-(difluoromethyl)thiazol-2-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.5]nonan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.5]nonan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.5]nonan-2-yl]methanone; 1-[[2-[6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]pyrazole-4-carbonitrile; 1-[[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]pyrazole-4-carbonitrile; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)imidazol-1-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-(trifluoromethyl)imidazol-1-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-[[4-(trifluoromethyl)imidazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(3-cyclopropyl-1,2,4-thiadiazol-5-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[(3-cyclopropyl-1,2,4-thiadiazol-5-yl)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-[(3-cyclopropyl-1,2,4-thiadiazol-5-yl)methyl]-2,6-diazaspiro[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-1,2,4-thiadiazol-5-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [7-[[5-(trifluoromethyl)isothiazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-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]-[7-[[5-(trifluoromethyl)isothiazol-3-yl]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-[[5-(trifluoromethyl)isothiazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [6-[[5-(trifluoromethyl)-1H-pyrazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1H-pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[4-(trifluoromethyl)thiazol-2-yl]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-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)thiazol-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]-[6-[[4-(trifluoromethyl)thiazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[5-methyl-4-(trifluoromethyl)thiazol-2-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-methyl-4-(trifluoromethyl)thiazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[(2-tert-butylthiazol-5-yl)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-tert-butylthiazol-5-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(2-tert-butylthiazol-5-yl)methyl]-2,6-diazaspiro[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-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]oxy-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-[1-(trifluoromethyl)cyclopropyl]pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[1-cyclopropyl-3-(trifluoromethyl)pyrazol-4-yl]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-[[1-cyclopropyl-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[1-cyclopropyl-3-(trifluoromethyl)pyrazol-4-yl]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-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[2-methyl-4-(trifluoromethyl)pyrazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [7-[[2-methyl-4-(trifluoromethyl)pyrazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-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]-[7-[[2-methyl-4-(trifluoromethyl)pyrazol-3-yl]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-[[2-methyl-4-(trifluoromethyl)pyrazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [6-[[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]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-methyl-3-(trifluoromethyl)pyrazol-1-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-[[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-methyl-5-(trifluoromethyl)pyrazol-1-yl]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-methyl-5-(trifluoromethyl)pyrazol-1-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-[[3-methyl-5-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-triazol-1-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-[[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-triazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(4-cyclobutylthiadiazol-5-yl)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-cyclobutylthiadiazol-5-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(4-cyclobutylthiadiazol-5-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [7-[[5-(trifluoromethyl)isoxazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-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]-[7-[[5-(trifluoromethyl)isoxazol-3-yl]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-[[5-(trifluoromethyl)isoxazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [6-[[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]methyl]-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]-[6-[[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[2-methyl-4-(trifluoromethyl)thiazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-methyl-4-(trifluoromethyl)thiazol-5-yl]methyl]-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]-[6-[[2-methyl-4-(trifluoromethyl)thiazol-5-yl]methyl]-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]-[6-(1-methylpyrazol-4-yl)oxy-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(4-cyclopropylthiadiazol-5-yl)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-cyclopropylthiadiazol-5-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(difluoromethyl)-3-methyl-pyrazol-1-yl]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-(difluoromethyl)-3-methyl-pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(difluoromethyl)-3-methyl-pyrazol-1-yl]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-(difluoromethyl)-5-methyl-pyrazol-1-yl]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-(difluoromethyl)-5-methyl-pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(difluoromethyl)-5-methyl-pyrazol-1-yl]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-[(4-tert-butyloxazol-2-yl)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-tert-butyloxazol-2-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(2,2,2-trifluoroethyl)pyrazol-3-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(2,2,2-trifluoroethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[5-[1-(trifluoromethyl)cyclopropyl]-1H-1,2,4-triazol-3-yl]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-[1-(trifluoromethyl)cyclopropyl]-1H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)triazol-1-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-(trifluoromethyl)triazol-1-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-[[5-(trifluoromethyl)-1,2,4-oxadiazol-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-[[4-(trifluoromethyl)thiazol-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(2,2,2-trifluoroethyl)triazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(2,2,2-trifluoroethyl)triazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]methyl]-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]-[6-[[3-methyl-1-(2,2,2-trifluoroethyl)pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[3-methyl-1-(2,2,2-trifluoroethyl)pyrazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-methyl-1-(2,2,2-trifluoroethyl)pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[5-methyl-1-(2,2,2-trifluoroethyl)pyrazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-methyl-1-(2,2,2-trifluoroethyl)pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(trifluoromethyl)pyrazol-3-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(trifluoromethyl)pyrazol-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)-1H-pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(trifluoromethyl)-1H-pyrazol-4-yl]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-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]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-[[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(3-cyclopropyl-1H-pyrazol-5-yl)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-1H-pyrazol-5-yl)methyl]-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-pyrazol-5-yl)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-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)-1,2,4-triazol-1-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-[[3-(trifluoromethyl)-1,2,4-triazol-1-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-[[3-(trifluoromethyl)-1,2,4-triazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[4-(trifluoromethyl)-1H-pyrazol-3-yl]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-(trifluoromethyl)-1H-pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-cyclopropyl-3-methyl-pyrazol-1-yl)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-cyclopropyl-3-methyl-pyrazol-1-yl)methyl]-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-[(5-cyclopropyl-3-methyl-pyrazol-1-yl)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-cyclopropyl-5-methyl-pyrazol-1-yl)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-5-methyl-pyrazol-1-yl)methyl]-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-5-methyl-pyrazol-1-yl)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-[[2-methyl-5-(trifluoromethyl)triazol-4-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-[[3-(trifluoromethyl)-1,2,4-oxadiazol-5-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-(2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[2-(2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol-3-yl]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-[[2-(2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(3-cyclopropyl-pyrazol-1-yl)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-cyclopropylpyrazol-1-yl)methyl]-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-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(2,2,2-trifluoroethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(trifluoromethyl)imidazol-1-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)imidazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)thiazol-2-yl]methyl]-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]-[6-[[5-(trifluoromethyl)thiazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(trifluoromethyl)thiazol-2-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)thiazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)isothiazol-5-yl]methyl]-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]-[6-[[3-(trifluoromethyl)isothiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(trifluoromethyl)isothiazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)isothiazol-5-yl]methyl]-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]-[6-[[5-(trifluoromethyl)isothiazol-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)isothiazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-methyl-4-(trifluoromethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[2-methyl-4-(trifluoromethyl)pyrazol-3-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-methyl-4-(trifluoromethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-5-(trifluoromethyl)pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-methyl-5-(trifluoromethyl)pyrazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-5-(trifluoromethyl)pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[2-ethyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[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-ethyl-5-(trifluoromethyl)pyrazol-3-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-ethyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[4-(trifluoromethyl)thiazol-2-yl]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-[[4-(trifluoromethyl)thiazol-2-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [7-[[4-(trifluoromethyl)thiazol-2-yl]methyl]-2,7-diazaspiro[3.5]nonan-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]-[7-[[4-(trifluoromethyl)thiazol-2-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [6-[[4-(trifluoromethyl)isothiazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)isothiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(trifluoromethyl)pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(trifluoromethyl)pyrazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(trifluoromethyl)pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(trifluoromethyl)isoxazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)isoxazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(difluoromethyl)thiazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(difluoromethyl)thiazol-2-yl]methyl]-2,6-diazaspiro[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-(difluoromethyl)thiazol-2-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(difluoromethyl)thiazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(trifluoromethyl)isoxazol-3-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)isoxazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[2-(2,2,2-trifluoroethyl)tetrazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(2,2,2-trifluoroethyl)tetrazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[2-(2,2,2-trifluoroethyl)triazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(2,2,2-trifluoroethyl)triazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(2,2,2-trifluoroethyl)tetrazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(2,2,2-trifluoroethyl)tetrazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[(4-tert-butylthiazol-2-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(4-tert-butylthiazol-2-yl)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-tert-butylthiazol-2-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-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-[[2-(2,2,2-trifluoroethyl)triazol-4-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-[[1-(2,2,2-trifluoroethyl)-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl]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-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[(5-tert-butyl-1,3,4-thiadiazol-2-yl)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-[(5-tert-butyl-1,3,4-thiadiazol-2-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-tert-butyl-1,3,4-thiadiazol-2-yl)methyl]-2,6-diazaspiro[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-(trifluoromethyl)oxazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(trifluoromethyl)oxazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[2-(trifluoromethyl)oxazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(trifluoromethyl)oxazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)oxazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[4-(trifluoromethyl)oxazol-2-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)oxazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(trifluoromethyl)isoxazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)isoxazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(trifluoromethyl)oxazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)oxazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[2-(2,2,2-trifluoroethyl)pyrazol-3-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(2,2,2-trifluoroethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(trifluoromethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[2-(trifluoromethyl)pyrazol-3-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(trifluoromethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[(4-dimethylphosphoryl-2-methyl-pyrazol-3-yl)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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-dimethylphosphoryl-2-methyl-pyrazol-3-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)-1H-1,2,4-triazol-5-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-[[3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(trifluoromethyl)-1H-imidazol-2-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1H-imidazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(2,2,2-trifluoroethyl)imidazol-2-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(2,2,2-trifluoroethyl)imidazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(trifluoromethyl)imidazol-2-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(trifluoromethyl)imidazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(trifluoromethyl)-1H-imidazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1H-imidazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[(4-cyclopropylthiazol-2-yl)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-cyclopropylthiazol-2-yl)methyl]-2,6-diazaspiro[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-(trifluoromethyl)-1H-pyrazol-3-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1H-pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-methyl-5-(trifluoromethyl)triazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-5-(trifluoromethyl)triazol-4-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-[(3-phenyl-1,2,4-oxadiazol-5-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[1-methyl-5-(trifluoromethyl)pyrazol-4-yl]oxy-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-[1-methyl-5-(trifluoromethyl)pyrazol-4-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[1-(2,2,2-trifluoroethyl)pyrazol-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-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; 2-methyl-4-[[2-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methyl]pyrazole-3-sulfonamide; 4-[[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]-2-methyl-pyrazole-3-sulfonamide; [6-[(4-tert-butyl-1H-imidazol-2-yl)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-tert-butyl-1H-imidazol-2-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-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-[[1-(2,2,2-trifluoroethyl)triazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(4-tert-butylisoxazol-3-yl)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-tert-butylisoxazol-3-yl)methyl]-2,6-diazaspiro[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-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(1H-pyrazol-3-ylmethyl)-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(1,1-difluoroethyl)-1,2,4-oxadiazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(1,1-difluoroethyl)-1,2,4-oxadiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[2-(2,2-difluoroethyl)pyrazol-3-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(2,2-difluoroethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(difluoromethyl)pyrazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(difluoromethyl)pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(cyclopropylmethyl)-1,2,4-oxadiazol-5-yl]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-[[3-(cyclopropylmethyl)-1,2,4-oxadiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(3-tert-butyl-1,2,4-oxadiazol-5-yl)methyl]-2,6-diazaspiro[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-5-methyl-isoxazol-4-yl)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-[(3-cyclopropyl-5-methyl-isoxazol-4-yl)methyl]-2,6-diazaspiro[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-5-methyl-isoxazol-4-yl)methyl]-2,6-diazaspiro[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-cyclopropyl-2-methyl-pyrazol-3-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-cyclopropyl-2-methyl-pyrazol-3-yl)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-[(5-cyclopropyl-2-methyl-pyrazol-3-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-cyclobutyl-1H-pyrazol-3-yl)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-[(5-cyclobutyl-1H-pyrazol-3-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(2-tert-butylpyrazol-3-yl)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-tert-butylpyrazol-3-yl)methyl]-2,6-diazaspiro[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-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(2-methylpyrazol-3-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[2-(difluoromethyl)thiazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(difluoromethyl)thiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; 1-methyl-5-[[2-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methyl]imidazole-4-carbonitrile; 5-[[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]-1-methyl-imidazole-4-carbonitrile; 5-[[2-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methyl]-1-methyl-imidazole-4-carbonitrile; [6-[(3-cyclopropyl-1H-pyrazol-5-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(1H-pyrazol-3-ylmethyl)-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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(pyrazolo[1,5-a]pyridin-3-ylmethyl)-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[(3-ethyl-1,2,4-thiadiazol-5-yl)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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(3-ethyl-1,2,4-thiadiazol-5-yl)methyl]-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]-[6-[[2-methyl-5-(trifluoromethyl)pyrazol-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-[[1-methyl-4-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(2,2,2-trifluoroethyl)pyrazol-4-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-[[1-(2,2,2-trifluoroethyl)pyrazol-4-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-[[4-(trifluoromethyl)triazol-2-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-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(difluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(difluoromethyl)-1H-pyrazol-5-yl]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-(difluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]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-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)-1H-pyrazol-5-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-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(3-cyclopropyl-1H-1,2,4-triazol-5-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-[(2,4-dimethylthiazol-5-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[(5-cyclopropyl-1H-1,2,4-triazol-3-yl)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-cyclopropyl-1H-1,2,4-triazol-3-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-[(1-methylimidazol-4-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-[(2-ethyl-4-methyl-1H-imidazol-5-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-[(2,4-dimethyloxazol-5-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-[(1-methylimidazol-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]-[6-[(1,5-dimethylpyrazol-4-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1H-pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(3,3,3-trifluoropropyl)pyrazol-3-yl]methyl]-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]-[6-[(4-mesylpyrazol-1-yl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[4-methyl-5-(trifluoromethyl)-1,2,4-triazol-3-yl]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-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.5]nonan-2-yl]methanone; [6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [7-[[3-(trifluoromethyl)isoxazol-5-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-cyclopropyl-1H-1,2,4-triazol-3-yl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(1-tert-butylimidazol-2-yl)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-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1H-1,2,4-triazol-3-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-[[1-(3,3,3-trifluoropropyl)pyrazol-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-[[4-methyl-5-(trifluoromethyl)-1,2,4-triazol-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)-1,2,4-oxadiazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethylsulfonimidoyl)pyrazol-1-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-[[5-(trifluoromethyl)-1,2,4-triazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)-1H-imidazol-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(4-mesylpyrazol-1-yl)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-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[3-(trifluoromethyl)isoxazol-5-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [6-[3-(1-aminocyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(2,2,2-trifluoroethyl)-1,2,4-triazol-3-yl]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-mesylpyrazol-1-yl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1,2,4-triazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(difluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-[1-(trifluoromethyl)cyclopropyl]-1H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(2,2,2-trifluoroethyl)triazol-4-yl]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-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)-1H-imidazol-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-[[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-5-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-[[1-(2,2,2-trifluoroethyl)-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[2-(2,2,2-trifluoroethyl)triazol-4-yl]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-[[4-(trifluoromethylsulfonimidoyl)pyrazol-1-yl]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-cyclopropyl-1H-pyrazol-3-yl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)-1H-pyrazol-3-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-(trifluoromethyl)-1,2,4-triazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1H-pyrazol-4-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-[[1-(2,2,2-trifluoroethyl)triazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[4-(trifluoromethyl)-1H-imidazol-2-yl]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-(trifluoromethylsulfonimidoyl)pyrazol-1-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-[[2-(2,2,2-trifluoroethyl)triazol-4-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-(trifluoromethyl)-1H-imidazol-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-[1-(trifluoromethyl)cyclopropyl]-1H-pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-triflylpyrazol-1-yl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[5-[1-(trifluoromethyl)cyclopropyl]-1H-pyrazol-3-yl]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-cyclopropylpyrazol-1-yl)methyl]-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-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-triflylpyrazol-1-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-[1-(trifluoromethyl)cyclopropyl]-1H-pyrazol-3-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-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-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-[[7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; and [6-(3-Cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[6-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone.

[0095] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is selected from: [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-5-(trifluoromethyl)pyrazol-4-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-[[1-methyl-5-(trifluoromethyl)pyrazol-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-[[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]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-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1H-1,2,4-triazol-3-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-(trifluoromethyl)-1H-1,2,4-triazol-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-[[1-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(trifluoromethyl)-1,2,4-thiadiazol-5-yl]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-(trifluoromethyl)-1,2,4-thiadiazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [7-[[5-(trifluoromethyl)-1H-pyrazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.5]nonan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.5]nonan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)imidazol-1-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-(trifluoromethyl)thiazol-2-yl]methyl]-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]-[6-[[4-[1-(trifluoromethyl)cyclopropyl]pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[1-cyclopropyl-3-(trifluoromethyl)pyrazol-4-yl]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-[[1-cyclopropyl-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-triazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[5-[1-(trifluoromethyl)cyclopropyl]-1H-1,2,4-triazol-3-yl]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-[1-(trifluoromethyl)cyclopropyl]-1H-1,2,4-triazol-3-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-(trifluoromethyl)triazol-1-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-(trifluoromethyl)-1H-pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(trifluoromethyl)-1H-pyrazol-4-yl]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-[[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(3-cyclopropyl-1H-pyrazol-5-yl)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-1H-pyrazol-5-yl)methyl]-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-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)-1,2,4-triazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[4-(trifluoromethyl)-1H-pyrazol-3-yl]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-(trifluoromethyl)-1H-pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-cyclopropyl-3-methyl-pyrazol-1-yl)methyl]-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-5-methyl-pyrazol-1-yl)methyl]-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-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(trifluoromethyl)thiazol-2-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)thiazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl]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-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-4-(trifluoromethyl)pyrazol-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-[[1-(2,2,2-trifluoroethyl)pyrazol-4-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-[[3-(difluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]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-(trifluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[2-(2,2,2-trifluoroethyl)triazol-4-yl]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-[[1-(2,2,2-trifluoroethyl)triazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[4-(trifluoromethyl)-1H-imidazol-2-yl]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-(trifluoromethylsulfonimidoyl)pyrazol-1-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-[[2-(2,2,2-trifluoroethyl)triazol-4-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-(trifluoromethyl)-1H-imidazol-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-triflylpyrazol-1-yl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; and [6-[[5-[1-(trifluoromethyl)cyclopropyl]-1H-pyrazol-3-yl]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.

[0096] 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-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone.

[0097] 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-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone.

[0098] 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-[[5-[1-(trifluoromethyl)cyclopropyl]-1H-1,2,4-triazol-3-yl]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.

[0099] 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-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-[1-(trifluoromethyl)cyclopropyl]-1H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone.

[0100] 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-[[5-(trifluoromethyl)-1H-pyrazol-4-yl]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.

[0101] 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-pyrazol-5-yl)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.

[0102] 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-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone.

[0103] 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.

[0104] In some embodiments, compounds of formula (I) are isotopically labeled by replacing one or more atoms therein with atoms having different atomic masses or mass numbers. Such isotopically labeled (i.e., radiolabeled) compounds of formula (I) are considered to be within the scope of the present disclosure. Exemplary 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% of a given isotope.

[0105] Heavier isotopes, such as deuterium, i.e. 2Substitutions such as H may result in greater metabolic stability, for example, a longer in vivo half-life or reduced dosage requirements, which may result in certain therapeutic advantages.

[0106] 11 C. 18 F, 15 O and 13 Substitution 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, by substituting an appropriate isotopically labeled reagent for a previously employed non-isotopically labeled reagent.

[0107] 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 techniques 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 otherwise indicated.

[0108] 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 (e.g., as described in "Protective Groups in Organic Chemistry," T.W. Greene and P.G.M. Hutts, 5th Edition (2014), John Wiley & Sons, New York) 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.

[0109] If the starting material or intermediate contains a stereocenter, the compound of formula (I) can be obtained as a mixture of diastereomers or enantiomers, which can be separated by methods well known in the art, such as chiral HPLC, chiral SFC, or chiral crystallization. Racemic compounds can be separated into their 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) typically results in the respective diastereomerically / enantiomerically enriched compounds of formula (I).

[0110] 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 several protecting groups one at a time without affecting other protecting groups in the molecule. The principle of orthogonal protection is well known in the art and 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).

[0111] Those skilled in the art will recognize that the reaction sequence may vary depending on the reactivity and nature of the intermediates.

[0112] More specifically, compounds of formula (I) can be prepared by the methods described below, the methods described in the Examples, or similar methods. Appropriate reaction conditions for the individual reaction steps are known to those skilled in the art. For literature-described reaction conditions that affect 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 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 produce the described intermediates and compounds. The reaction sequence is not limited to the sequence shown in the scheme, but the order of the reaction steps can be freely changed depending on the starting materials and their respective reactivities.

[0113] 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.

[0114] The following abbreviations are used herein: Ac = acetyl, ACN = acetonitrile, Bn = benzyl, BINAP = (2,2'-bis(diphenylphosphino)-1,1'-binaphthyl), Boc = tert-butyloxycarbonyl, CAS RN = Chemical Abstracts Registry Number, Cbz = benzyloxycarbonyl, CMBP = (cyanomethylene)tributylphosphorane, 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, dba = dibenzylideneacetone, DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene, DCE = 1,2-dichloroethane, DCM = dichloromethane, DEAD = diethyl azodicarboxylate, DIAD = diisopropyl azodicarboxylate, DIBAL-H = diisobutylaluminum hydride, DMAP = 4-dimethylaminopyridine, DME = dimethoxyethane, DME DA = N,N'-dimethylethylenediamine, DMF = N,N-dimethylformamide, DMF-DMA = N,N-dimethylformamide dimethyl acetal, DMSO = dimethyl sulfoxide, DIPEA (or DIEA) = 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 LAH = 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 = mesyl, MS = mass spectrum, MTBE = methyl tert-butyl ether, nBuLi = n-butyllithium, NaBH3CN = sodium cyanoborohydride, NaH = sodium hydride, NaHMDS = sodium bis(trimethylsilyl)amide, 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 = propyl phosphonic anhydride, PE = petroleum ether, PG = protecting group, Pd-C = palladium on 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 = reverse 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 = tosyl, TS-TPP = triphenylphosphine-polymer-bound, ZnCl = zinc chloride, prep-TLC = preparative thin-layer chromatography.

[0115] The present compounds of formula I can be prepared by reacting an activated intermediate of formula 2 with a nucleophilic amine 1 by heating in a solvent such as DMF or CHCN in the presence of a base such as DIPEA. (Scheme 1) Alternatively, the activated intermediate can be formed onto other coupling partners (1) to produce ureas of formula I. [ka] Scheme 1

[0116] 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, either transiently in the reaction mixture or in the presence of a base such as DIPEA (Scheme 2). Alternatively, the same strategy as in Schemes 1 and 2 can be used, but the activated intermediate can be first built on amine 1 before coupling with amine 3. [ka] Scheme 2

[0117] Building blocks of formula 4 where L = CH and Y = CH can be generated by Suzuki reaction (e.g., (Pd(dppf)Cl, KCO, dioxane / HO), (X = Br, I), followed by hydrogenation (e.g., Pd / C, H). The requisite boronate intermediate 5 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 3). When B = N-linked heteroaryl, a Chan-Lam-type coupling can be used in place of the Suzuki reaction, followed by hydrogenation / deprotection. [ka] Scheme 3

[0118] Alternatively, building blocks of formula 8 where L=CH and Y=N can be prepared by reductive amination of aldehyde 9 with a suitably protected spirocycle 10 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 4). [ka] Scheme 4

[0119] Alternatively, components of formula 8 where L = CH2 and Y = N can be prepared by reductive amination of a suitably protected spirocycle 10 with (hetero)arylmethyl halides (X = Br, I, Cl) 11 in the presence of a base such as K2CO3 in a solvent such as ACN, followed by deprotection under standard conditions (e.g., with TsOH when PG = Boc) (Scheme 5). [ka] Scheme 5

[0120] Alternatively, components of formula 12 can be prepared by a Mitsunobu-type reaction of heterocycle B (13) with hydroxyl component 14 (e.g., using diisopropyl azodicarboxylate and triphenylphosphine, or Tsunoda's reagent (cyanomethylenetrimethylphosphorane)), followed by deprotection under standard conditions (e.g., with TsOH when PG = Boc). (Scheme 6) Alternatively, components of formula 12 can be prepared by converting hydroxyl component 14 to a mesylate (e.g., with MsCl, Et3N), followed by deprotection of heterocycle B (13) with S in the presence of a base such as NaH. N It can be prepared by reacting [ka] Scheme 6

[0121] Alternatively, components of formula 15 where B is a C-linked heteroaryl and L = -CH2- can be prepared using standard heterocyclic synthesis techniques starting from the appropriate carboxylic acid or (16) or ester, nitrile (17) or diketone (18) derivatives. The nitrile derivatives can be prepared from the hydroxyl derivative (19) by conversion to the mesylate (e.g., with MsCl, Et3N) followed by conversion of the mesylate group to S with cyanide. N The diketone derivatives can be generated by disubstitution (e.g., with KCN). The diketone derivatives can be generated from the commercially available ester derivatives (20) (Scheme 7). A similar sequence can also be applied when B is a C-linked heteroaryl, L = -CH2-, and the spiro unit is N-linked (i.e., Y = N). [ka] Scheme 7

[0122] Alternatively, building blocks of formula 21, where L = oxygen, Y = CH, and B = (hetero)aryl, can be prepared by reacting a suitably protected (spiro)cyclic amine (23) bearing a hydroxyl group with a nucleophilic (hetero)aryl alcohol (22) under Mitsunobu-type conditions (e.g., using Tsunoda's reagent, (tributylphosphoranylidene)acetonitrile, or PPh3 / DIAD), followed by deprotection (Scheme 8). [ka] Scheme 8

[0123] The (hetero)aryltrifluoromethylcyclopropyl building block 24 is not generally available and was instead generated from halide building block 25 (X = I, Br) by Suzuki reaction with 1-(trifluoromethyl)vinylboronic acid to give 26. Cyclopropanation using diphenyl(methyl)sulfonium tetrafluoroborate and LiHMDS afforded the required building block 24. (Scheme 9) This sequence can also be carried out in other synthetic schemes, for example, between steps of the N-linked heteroaryl ring B; these functionalization steps can also be carried out after the Suzuki / hydrogenation sequence but before final deprotection while preparing the building block of formula 4 (see Scheme 3). Alternatively, the (hetero)aryltrifluoromethylcyclopropyl building block can be generated from commercially available building blocks via standard heterocyclic synthesis techniques. [ka] Scheme 9

[0124] Building blocks of formula 3 where A is an N-linked heterocycle can be prepared by reacting the nucleophilic heterocycle A (27) with an appropriately protected building block 28 (X=OMs, a leaving group such as I, Br, etc.) in the presence of a base such as CsCO or NaH, followed by deprotection under standard conditions (e.g., with TsOH if PG=Boc, or palladium-catalyzed hydrogenation if PG=Cbz) (Scheme 10). Typically, mesylate building blocks 28 are used (X=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] Scheme 10

[0125] Building blocks of formula 3 where A is a C-linked heterocycle can be prepared by standard heterocyclic techniques. For example, building block 29 where the A ring is a pyrazole can be generated by Knorr-type pyrazole synthesis from hydrazine and diketone 32. The required diketone can be generated by reaction of the appropriate ketone 30 with acid derivative 31 (X = leaving group, e.g., OAc, OMe) in the presence of base (e.g., NaH, LDA), followed by deprotection under standard conditions (Scheme 11). [ka] Scheme 11

[0126] Alternatively, A-C-linked building blocks of formula 3 can be generated by metal-catalyzed cross-coupling reactions using appropriately functionalized intermediates 33 and 34 (X = reactive group), where one partner typically bears an organometallic (e.g., zincate, boronate) generated from a halide intermediate such as I or Br, and the other partner bears a halide such as Br or I, followed by deprotection under standard conditions (Scheme 12). [ka] Scheme 12

[0127] In some cases, compounds of Formula I may also be produced by combining steps already described in new combinations, for example, by performing the coupling of Scheme 1 before completing the individual building blocks using the same sequence as above. In some cases, additional protection and deprotection steps were used before, after, or simultaneously with existing synthetic steps.

[0128] In some cases, compounds of Formula I can be further functionalized to obtain 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 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 obtain other building blocks of Formula 1.

[0129] In some cases, standard functional group interconversion techniques (e.g., installation of halides (e.g., with NIS or NBS), removal of halides (e.g., under hydrogenation conditions), conversion of halides to other groups, such as lower amines or lower alkyls, using metal-catalyzed cross-coupling conditions such as the Buchwald or Suzuki reaction, conversion of iodides to trifluoromethyl groups using trifluoromethylation reagents (e.g., diphenyl(trifluoromethyl)sulfonium trifluoromethanesulfonate), installation and removal of protecting groups, hydrolysis of esters to acids, formation of amides from acids and small amines, conversion of boron-containing groups to hydroxyls using alkaline peroxide conditions, cycloaddition of azidotrimethylsilane with nitriles to form tetrazoles, Sandmeyer reaction of anilines with bromides, oxidation of thioethers to sulfones, oxidation of thioethers to sulfoximines using PhI(OAc)2 and NH2COONH4, S N Building blocks can be generated from commercially available fragments using alkylation of hydroxyl or amine groups via the 2 reaction or reductive amination; acylation with activated carbonyl derivatives; installation of -SO2Me or -SO2CF3 groups from iodo- or bromo-building blocks using literature techniques; installation of small alkyl groups or rings such as cyclopropyl groups on heteroaromatic nitrogens using boronic acid derivatives under Chan-Lam-type conditions; or installation of dimethylphosphoryl groups in place of (hetero)aromatic halide (X = Br, I) groups via Pd-catalyzed cross-coupling with dimethylphosphine oxide in the presence of a base such as Et3N. Such techniques can also be used to elaborate commercially available fragments before, after, or intermediate the above synthetic sequences. In some cases, building blocks can be generated from commercially available fragments using standard heterocyclic synthesis techniques (e.g., synthesis of pyrazoles, oxadiazoles, imidazoles).

[0130] 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 1-12.

[0131] In one aspect, the present invention provides a method for preparing a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, comprising: [ka] (Wherein A and R 3 is as described herein) with a compound of formula 1; [ka] (In the formula, R 1 , R 2 , B, L, W, Y and Z are as described herein) with a compound of formula (I) by heating in a solvent such as DMF or CHCN in the presence of a base such as DIPEA to form said compound of formula (I).

[0132] 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.

[0133] MAGL inhibitory activity The compounds of the invention are MAGL inhibitors. Thus, in one aspect, the invention provides the use of a compound of formula (I) as described herein for inhibiting MAGL in a mammal.

[0134] 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.

[0135] 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.

[0136] In a further aspect, the present invention provides a method for inhibiting MAGL in a mammal, comprising administering to the mammal an effective amount of a compound of formula (I) as described herein.

[0137] 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. Hereinafter, this assay is 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 with an acetonitrile / water liquid setup. The mass spectrometer was operated in negative electrospray mode, following the mass transitions of arachidonic acid (303.1 → 259.1) and d8-arachidonic acid (311.1 → 267.0). Compound activity was calculated based on the intensity ratio (arachidonic acid / d8-arachidonic acid). [Table 1] TIFF2025536386000055.tif241170 TIFF2025536386000056.tif241170 TIFF2025536386000057.tif241170 TIFF2025536386000058.tif241170 TIFF2025536386000059.tif241170 TIFF2025536386000060.tif241170

[0138] 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.

[0139] 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.

[0140] 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 a disease or disorder associated with monoacylglycerol lipase in a mammal.

[0141] In a further aspect, the present invention provides a method for treating or preventing a disease or disorder associated with monoacylglycerol lipase in a mammal, the method comprising administering to the mammal a therapeutically effective amount of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof.

[0142] 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, in the preparation of a medicament for treating or preventing a disease or disorder associated with monoacylglycerol lipase in a mammal.

[0143] 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 treating or preventing a disease or disorder associated with monoacylglycerol lipase in a mammal.

[0144] In one embodiment, the disease or disorder associated with monoacylglycerol lipase is selected from neuroinflammation, neurodegenerative diseases, pain, cancer, psychiatric disorders and / or inflammatory bowel disease.

[0145] In one embodiment, the disease or condition associated with monoacylglycerol lipase 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, visceral pain, and inflammatory bowel disease.

[0146] In one embodiment, the disease or disorder associated with monoacylglycerol lipase is selected from neuroinflammation, neurodegenerative diseases, pain, cancer, psychiatric disorders, and inflammatory bowel disease in a mammal.

[0147] In one embodiment, the disease or disorder associated with monoacylglycerol lipase is selected from multiple sclerosis, Alzheimer's disease, and Parkinson's disease in a mammal.

[0148] In one embodiment, the disease or disorder associated with monoacylglycerol lipase is multiple sclerosis.

[0149] In one embodiment, the disease or disorder associated with monoacylglycerol lipase is selected from neuroinflammatory and neurodegenerative diseases.

[0150] In one embodiment, the disease or disorder associated with monoacylglycerol lipase is a neurodegenerative disease.

[0151] In one embodiment, the disease or disorder associated with monoacylglycerol lipase is cancer.

[0152] In one embodiment, the disease or disorder associated with monoacylglycerol lipase is inflammatory bowel disease.

[0153] In one embodiment, the disease or disorder associated with monoacylglycerol lipase is pain.

[0154] 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.

[0155] In one embodiment, a pharmaceutical composition according to Example 310 or Example 311 is provided.

[0156] The compound of formula (I) and its pharmaceutically acceptable salts can be used as medicines (for example, in the form of pharmaceutical preparations).The pharmaceutical preparations can be administered to the body orally (for example, in the form of tablets, coated tablets, dragees, hard and soft gelatin capsules, solutions, emulsions or suspensions), nasally (for example, in the form of nasal drops), or rectally (for example, in the form of suppositories).However, administration can also be carried out parenterally, such as intramuscularly or intravenously (for example, in the form of injections).

[0157] The compound of formula (I) and its pharmaceutically acceptable salts can be processed with pharmaceutically inert inorganic or organic adjuvants for the preparation 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.

[0158] Suitable adjuvants for soft gelatin capsules are, for example, vegetable oils, waxes, fats, semisolid substances, and liquid polyols.

[0159] Suitable adjuvants for the production of solutions and syrups are, by way of example, water, polyols, saccharose, invert sugar, glucose etc.

[0160] Suitable adjuvants for injection solutions are, for example, water, alcohols, polyols, glycerol, vegetable oils and the like.

[0161] Suitable adjuvants for suppositories are, for example, natural or hardened oils, waxes, fats, semi-solid or liquid polyols etc.

[0162] 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.

[0163] Dosage can vary widely and will of course be adapted to the individual requirements of each particular case.Generally, for oral administration, a daily dosage 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 if indicated. [Example]

[0164] The present invention will be more fully understood by reference to the following examples, which should not, however, be construed as limiting the scope of the claims to the examples.

[0165] Where preparations are obtained as mixtures of enantiomers, the pure enantiomers may 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.

[0166] Unless otherwise stated, all reactions and intermediates were prepared under an argon atmosphere.

[0167] Example 1 [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-5-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone [ka] To a solution of 1-[1-(2-azaspiro[3.3]heptan-6-yl)-1,2,4-triazol-3-yl]cyclopropanol; 2,2,2-trifluoroacetic acid (A.2) (80 mg, 0.120 mmol) in N,N-dimethylformamide (0.631 mL) cooled to 0° C., DIPEA (108 mg, 146 μL, 0.838 mmol) was added, followed by bis(1,2,4-triazol-1-yl)methanone (19.6 mg, 0.120 mmol), after which the reaction mixture was stirred at 0° C. for 30 min. 6-[[1-Methyl-5-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptane; 4-methylbenzenesulfonic acid (B.308) (54.2 mg, 0.126 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 afford the title compound as a colorless gum (38.9 mg). MS (ESI): m / z=506.3 [M+H] +

[0168] Similar to Example 1, the examples in the table below were prepared by urea coupling using the respective building blocks AX and BX.

Table 2

[0169] Example 330 [6-[3-(1-aminocyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone [ka] To N-[1-[1-(2-azaspiro[3.3]heptan-6-yl)-1,2,4-triazol-3-yl]cyclopropyl]carbamic acid tert-butyl ester; acetic acid (A.7) (145 mg, 306 μmol) in N,N-dimethylformamide (1.78 mL) cooled to 0° C. was added DIPEA (276 mg, 373 μL, 2.14 mmol) followed by bis(1,2,4-triazol-1-yl)methanone (52.7 mg, 321 μmol), after which the reaction mixture was stirred at 0° C. for 30 min. 6-[[1-Methyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane; 4-methylbenzenesulfonic acid (P.7) (152 mg, 352 μmol) was added to the reaction mixture, which was then stirred at 50° C. for 18 hours. The volatiles were removed in vacuo, and the crude residue was dissolved in dichloromethane (1.72 mL), followed by the addition of TFA (697 mg, 471 μL, 6.11 mmol), after which the reaction mixture was stirred at room temperature for 18 hours. The volatiles were removed in vacuo, the crude residue was dissolved in DMF, and the crude solution was directly subjected to purification by reverse-phase HPLC to afford the title compound as a colorless gum (6.7 mg). MS (ESI): m / z = 505.4 [M+H] +

[0170] Step a) N-[1-(1H-1,2,4-triazol-3-yl)cyclopropyl]carbamic acid tert-butyl ester A suspension of N-(1-carbamoylcyclopropyl)carbamic acid tert-butyl ester (CAS: 507264-66-6) (4630 mg, 22.7 mmol) in DMF-DMA (54.0 g, 60.7 mL, 453 mmol) was stirred at 55 °C for 1.5 h. Volatiles were removed in vacuo, and the resulting crude residue was dissolved in 1,4-dioxane (80 mL). Subsequently, 35% aqueous hydrazine (5.19 g, 5.08 mL, 56.7 mmol) and acetic acid (3.4 g, 3.24 mL, 56.7 mmol) were added, after which the reaction mixture was stirred at 70 °C for 4 h. The reaction mixture was poured into a separatory funnel containing EtOAc and saturated aqueous NH4Cl. After extraction, 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 crude title compound (5.04 g) as a pale pink solid, which was used without further purification. MS (ESI): m / z = 169.0 [M-C4H8+H] +

[0171] Step b) 6-[3-[1-(tert-butoxycarbonylamino)cyclopropyl]-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carboxylic acid benzyl ester To a solution of 6-methylsulfonyloxy-2-azaspiro[3.3]heptane-2-carboxylic acid benzyl ester (CAS: 2966056-53-9) (7.69 g, 23.6 mmol) in N,N-dimethylformamide (102 mL) was added N-[1-(1H-1,2,4-triazol-3-yl)cyclopropyl]carbamic acid tert-butyl ester (5.05 g, 22.5 mmol) and cesium carbonate (11.0 g, 33.8 mmol), after which the reaction mixture was stirred at 100 °C for 18 h. The volatiles were removed in vacuo, and the crude residue was partitioned between ethyl acetate and water. The organic phase was collected, and the aqueous layer was back-extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and evaporated to dryness to give 11.5 g of crude residue, which was purified by flash chromatography (eluent heptane / ethyl acetate 5% to 75%) to give the title compound (4.22 g) as a white solid. MS (ESI): m / z = 454.3 [M+H] + NOTE: The title compound was produced along with a regioisomeric by-product. Identity was confirmed by NMR analysis.

[0172] Step c) N-[1-[1-(2-azaspiro[3.3]heptan-6-yl)-1,2,4-triazol-3-yl]cyclopropyl]carbamic acid tert-butyl ester; acetic acid (A.7) A solution of 6-[3-[1-(tert-butoxycarbonylamino)cyclopropyl]-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carboxylic acid benzyl ester (4160 mg, 9.17 mmol) in methanol (30 mL) and AcOH (1.57 mL) in a pressure vessel was placed under argon. Catalyst, 20% Pd(OH)2 / C (wet), was added (416 mg), and the vessel was refined and filled with hydrogen. The reaction was stirred under H2 (3 bar) at 40 °C for 18 h, cooled, and filtered. The vessel and filter cake were rinsed with methanol. The filtrate was evaporated to dryness to give 4.3 g of the crude title compound, which was used without further purification (approximately 80% purity). MS (ESI) m / z = 320.3 [M+H] +

[0173] Composition of Components Example A.1 6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane; 4-methylbenzenesulfonic acid [ka] A solution of tert-butyl 6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate (560 mg, 1.84 mmol) in ethyl acetate (35.6 mL) was treated with 4-methylbenzenesulfonic acid monohydrate (350 mg, 1.84 mmol) at 23 °C. The mixture was heated to 80 °C and stirred at this temperature for 1 h, then cooled and evaporated. The residue was treated with DCM and EtO and allowed to stand at 0 °C for 16 h. The resulting solid was filtered and dried to give the desired product (6.0 g, 86% yield) as an off-white solid. MS (ESI): m / z = 205.2 [M+H-Tos] +

[0174] Step a): 6-hydroxy-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester To a solution of tert-butyl 6-oxo-2-azaspiro[3.3]heptane-2-carboxylate (CAS RN: 1181816-12-5; 20 g, 94.67 mmol) in MeOH (197.24 mL) was added NaBH (7.16 g, 189.34 mmol) under N at 0 °C. The mixture was stirred at 0 °C for 1 h and then evaporated. The residue was dissolved in saturated aqueous NaHCO and the aqueous solution was extracted with DCM. The combined organic layers were dried over MgSO, filtered, and evaporated to give the title compound (19 g, 94% yield) as a white solid. MS (ESI): m / z = 158.1 [M+H] +

[0175] Step b): tert-Butyl 6-methylsulfonyloxy-2-azaspiro[3.3]heptane-2-carboxylate Two batches were run in parallel. To a solution of tert-butyl 6-hydroxy-2-azaspiro[3.3]heptane-2-carboxylate (100 g, 468.9 mmol) in DCM (1000 mL) was added TEA (128.0 g, 1172.2 mmol) at 23 °C. The reaction mixture was then cooled to 0 °C, and MsCl (81.49 g, 703.3 mmol) was added dropwise. The mixture was stirred at 25 °C for 16 h, after which both batches were combined and poured into water (2 L). The organic layer was separated, washed with brine (2 × 2000 mL), dried over NaSO, filtered, and evaporated to give the title compound (269 g, quantitative) as a crude white solid, which was used directly in the next step.

[0176] Step c): tert-butyl 6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate To a mixture of 3-cyclopropyl-1H-1,2,4-triazole (112.37 g, 1029.65 mmol), tert-butyl 6-methylsulfonyloxy-2-azaspiro[3.3]heptane-2-carboxylate (250.0 g, 858.05 mmol) in ACN (2500 mL) was added cesium carbonate (559.14 g, 1716.09 mmol). The mixture was stirred at 70 °C for 16 h, then filtered and evaporated. Purification by FC (SiO; DCM / THF / PE) afforded the desired compound (1.10 g, 40.0% yield) as a yellow solid. MS (ESI): m / z = 305.3 [M+H] +

[0177] Example A.2 1-[1-(2-Azaspiro[3.3]heptan-6-yl)-1,2,4-triazol-3-yl]cyclopropanol;2,2,2-Trifluoroacetic acid [ka] To a solution of 6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (6.23 g, 19.06 mmol) in DCM (80 mL) was added TFA (14.68 mL, 190.56 mmol) and the reaction mixture was stirred at 23 °C for 18 h. MS (ESI): m / z = 221.2 [M+H] +

[0178] Step a): 3-(1-benzoxycyclopropyl)-1H-1,2,4-triazole A solution of 1-benzoxycyclopropanecarboxamide (CAS RN: 865798-45-4; 9.05 g, 44.96 mmol) in DMF-DMA (120 mL, 899 mmol) was stirred at 90 °C for 2.5 h, then cooled and evaporated. The residue was dissolved in 1,4-dioxane (110 mL) and treated with 35% aqueous hydrazine (8.06 mL, 89.92 mmol) and acetic acid (5.15 mL, 89.92 mmol). The mixture was stirred at 90 °C for 18 h, then cooled and evaporated. The residue was dissolved in 150 mL of ethyl acetate and poured into a separatory funnel containing 100 mL of saturated aqueous NH4Cl. After extraction, the organic phase was collected, and the aqueous layer was back-extracted with 150 mL of ethyl acetate. The combined organic phases were dried over sodium sulfate and evaporated to give the desired crude product (10.45 g, 97% yield). MS (ESI): m / z = 216.2 [M+H] +

[0179] Step b): 6-Hydroxy-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester To a solution of tert-butyl 6-oxo-2-azaspiro[3.3]heptane-2-carboxylate (CAS RN: 1181816-12-5; 20 g, 94.67 mmol) in MeOH (197.24 mL) was added NaBH (7.16 g, 189.34 mmol) under N at 0 °C. The mixture was stirred at 0 °C for 1 h and then evaporated. The residue was dissolved in saturated aqueous NaHCO and the aqueous solution was extracted with DCM. The combined organic layers were dried over MgSO, filtered, and evaporated to give the title compound (19 g, 94% yield) as a white solid. MS (ESI): m / z = 158.1 [M+H] +

[0180] Step c): tert-Butyl 6-methylsulfonyloxy-2-azaspiro[3.3]heptane-2-carboxylate Two batches were run in parallel. To a solution of tert-butyl 6-hydroxy-2-azaspiro[3.3]heptane-2-carboxylate (100 g, 468.9 mmol) in DCM (1000 mL) was added TEA (128.0 g, 1172.2 mmol) at 23 °C. The reaction mixture was then cooled to 0 °C, and MsCl (81.49 g, 703.3 mmol) was added dropwise. The mixture was stirred at 25 °C for 16 h, after which both batches were combined and poured into water (2 L). The organic layer was separated, washed with brine (2 × 2000 mL), dried over NaSO, filtered, and evaporated to give the title compound (269 g, quantitative) as a crude white solid, which was used directly in the next step.

[0181] Step d): tert-butyl 6-[3-(1-benzyloxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of 3-(1-benzyloxycyclopropyl)-1H-1,2,4-triazole (22.0 g, 102.21 mmol) in NMP (220 mL) was added NaH (4.42 g, 183.97 mmol) under nitrogen at 0 °C. The resulting yellow solution was stirred at 0 °C for 30 min and then treated with tert-butyl 6-methylsulfonyloxy-2-azaspiro[3.3]heptane-2-carboxylate (44.67 g, 153.31 mmol). The mixture was heated to 90 °C and stirred at this temperature for 12 h. The mixture was cooled, diluted with 800 mL of saturated aqueous NH Cl solution, and extracted with EtOAc. The combined organic layers were washed with 400 mL of brine, dried over Na SO , filtered, and evaporated. Purification by FC (SiO ; PE / EtOAc) afforded the desired product (22.22 g, 51.95% yield) as a yellow solid. MS (ESI): m / z = 411.1 [M+H] +

[0182] Step e): 6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester A solution of 6-[3-(1-benzoxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (40 g, 97.44 mmol) in THF (400 mL) was placed under Ar and treated with 5% wet Pd / C (7.0 g, 1488.8 mmol). The mixture was placed under an H atmosphere and stirred at 50 °C and 2 bar for 5 h, then returned to an Ar atmosphere, filtered, and evaporated. Purification by FC (SiO; heptane / EtOAc / EtOH) afforded the desired product (26.25 g, 85% yield) as a white solid. MS (ESI): m / z = 321.3 [M+H] +

[0183] Example A.3 6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane; 4-Methylbenzenesulfonic acid [ka] A mixture of tert-butyl 6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carboxylate (33.0 g, 99.3 mmol) and p-toluenesulfonic acid (20.52 g, 119.16 mmol) in EtOAc (330 mL) was stirred at 80 °C for 12 h, then cooled to 23 °C and evaporated. The residue was treated with water and lyophilized to give the desired compound (40.0 g, 95.43% yield) as a yellow solid. MS (ESI): m / z = 233.1 [M-TsOH+H] +

[0184] Step a): tert-butyl 6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carboxylate A solution of 3-(trifluoromethyl)-1H-1,2,4-triazole (CAS RN: 60406-75-9; 7.56 g, 55.18 mmol) in DMF (150 mL) was treated with 60% sodium hydride in oil (2.21 g, 55.18 mmol) at 0 °C under Ar. The mixture was stirred at 20 °C for 1 h, and tert-butyl 6-bromo-2-azaspiro[3.3]heptane-2-carboxylate (CAS RN: 2409962-67-8; 12.7 g, 45.99 mmol) in DMF (15 mL) was added in one portion. The mixture was stirred at 90 °C for 15 h, cooled, and diluted with water. The mixture was extracted with EtOAc, and the organic layer was washed with brine, dried over Na SO , and evaporated. Purification by FC (SiO2; PE / EtOAc) gave the desired compound (10.7 g, 70.02% yield) as a white solid. MS (ESI): m / z = 277.2 [M-Bu + H] +

[0185] Example A.4 6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptane; 2,2,2-trifluoroacetic acid [ka] To a solution of 6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (1.80 g, 5.93 mmol) in dichloromethane (21 mL) was added TFA (4.57 mL, 59.33 mmol) at 23 °C. The mixture was stirred at this temperature for 18 h and then evaporated to give the desired compound (3.69 g, quantitative) as a pale yellow viscous oil. MS (ESI): m / z = 204.2 [M+H] +

[0186] Step a): tert-butyl 6-(3-cyclopropyl-3-oxo-propanoyl)-2-azaspiro[3.3]heptane-2-carboxylate To a solution of O2-tert-butyl O6-methyl 2-azaspiro[3.3]heptane-2,6-dicarboxylate (9.0 g, 35.25 mmol) in THF (180 mL) was added cyclopropyl methyl ketone (2.96 g, 35.25 mmol) and NaH (2.37 g, 98.7 mmol) at 20 °C. The mixture was stirred at 60 °C for 12 h, then cooled and diluted with water (200 mL). The mixture was extracted with EtOAc, and the combined organic layers were dried over Na2SO4, filtered, and evaporated. Purification by FC (PE / EtOAc) afforded the desired product (4.9 g, 45.2% yield) as a yellow solid.

[0187] Step b): tert-butyl 6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptane-2-carboxylate A mixture of tert-butyl 6-(3-cyclopropyl-3-oxo-propanoyl)-2-azaspiro[3.3]heptane-2-carboxylate (1.0 g, 3.25 mmol), hydrazine hydrate (325.72 mg, 6.51 mmol) in 1,4-dioxane (20 mL) was stirred at 90 °C for 12 h. The reaction was diluted with 50 mL of water and extracted with EtOAc. The combined organic layers were washed with 25 mL of brine, dried over Na2SO4, filtered, and evaporated. Purification by FC (SiO2, PE / EtOAc) afforded the desired product (930.0 mg, 94.22% yield) as a yellow solid. MS (ESI): m / z = 248.1 [M+H] +

[0188] Example A.5 1-[5-(2-Azaspiro[3.3]heptan-6-yl)-1H-pyrazol-3-yl]cyclopropanol;2,2,2-Trifluoroacetic acid [ka] To a solution of 6-[3-(1-hydroxycyclopropyl)-1H-pyrazol-5-yl]-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (383 mg, 1.2 mmol) in dichloromethane (4 mL) was added TFA (923.81 μL, 11.99 mmol). The mixture was stirred at 23 °C for 18 h and then evaporated to give the desired crude product (794 mg, quantitative) as a pale yellow viscous oil. MS (ESI): m / z = 220.2 [M+H] +

[0189] Step a): 1-[tert-butyl(diphenyl)silyl]oxy-N-methoxy-N-methyl-cyclopropanecarboxamide To a solution of 1-[tert-butyl(diphenyl)silyl]oxycyclopropanecarboxylic acid (CAS RN: 2813270-40-3; 2.70 g, 7.93 mmol) in DMF (30 mL) was added HATU (3.62 g, 9.52 mmol) and DIPEA (3586.94 mg, 27.75 mmol) at 25 °C. After 0.1 h, N-methoxymethanamine hydrochloride (927.78 mg, 9.52 mmol) was added at 20 °C, and the resulting mixture was stirred at 20 °C for 12 h. The reaction mixture was diluted with HO (50 mL) and extracted with EtOAc. The combined organic layers were washed with saturated aqueous NaCl, dried over anhydrous NaSO, filtered, and evaporated. Purification by FC (SiO; PE / EtOAc) afforded the desired compound (2.8 g, 92.06% yield) as a yellow oil.

[0190] Step b): 1-[1-[tert-butyl(diphenyl)silyl]oxycyclopropyl]ethanone To a solution of 1-[tert-butyl(diphenyl)silyl]oxy-N-methoxy-N-methyl-cyclopropanecarboxamide (2.80 g, 7.3 mmol) in THF (30 mL) was added methylmagnesium bromide (0.6605 mL, 3 M in diethyl ether) at 0 °C, and the reaction mixture was stirred at 20 °C for 2 h. The reaction mixture was quenched by the addition of saturated aqueous NH Cl (50 mL) at 25 °C, then diluted with HO (50 mL) and extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na SO , filtered, and evaporated to give the desired compound (2.0 g, 80.93% yield) as a yellow oil.

[0191] Step c): 1-[1-[tert-butyl(diphenyl)silyl]oxycyclopropyl]ethanone A solution of 2-tert-butoxycarbonyl-2-azaspiro[3.3]heptane-6-carboxylic acid (3000.0 mg, 12.43 mmol) and TEA (1.89 mL, 13.68 mmol) in DCM (30 mL) was treated with 2-methylpropyl carbonochloridate (1.87 g, 13.68 mmol) at 0 °C. The mixture was stirred at 20 °C for 12 h, then treated with water (100 mL) and extracted with EtOAc. The combined organic layers were dried over anhydrous NaSO, filtered, and evaporated to give the desired compound (4.2 g, 98.94% yield) as a yellow oil.

[0192] Step d): tert-butyl 6-[3-[1-[tert-butyl(diphenyl)silyl]oxycyclopropyl]-3-oxo-propanoyl]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of 1-[1-[tert-butyl(diphenyl)silyl]oxycyclopropyl]ethanone (2000.0 mg, 5.91 mmol) in THF (40 mL) was added LDA (5.91 mL, 11.82 mmol) (2 M in THF) under Ar at −78° C. The mixture was stirred at this temperature for 1 h and then treated with O2-tert-butyl O6-isobutoxycarbonyl 2-azaspiro[3.3]heptane-2,6-dicarboxylate (4034.03 mg, 11.82 mmol). The mixture was stirred at this temperature for an additional 1 h and allowed to warm to 0° C. Water (30 mL) was added and the mixture was extracted with EtOAc. The combined organic layers were washed with saturated aqueous NaCl, dried over Na2SO4, filtered, and evaporated. Purification by FC (SiO2; PE / EtOAc) gave the desired compound (2.0 g, 60.3% yield) as a yellow oil. MS (ESI): m / z = 484.3 [M+H] +

[0193] Step e): tert-butyl 6-[3-(1-hydroxycyclopropyl)-1H-pyrazol-5-yl]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[3-[1-[tert-butyl(diphenyl)silyl]oxycyclopropyl]-3-oxo-propanoyl]-2-azaspiro[3.3]heptane-2-carboxylate (2.0 g, 3.56 mmol) in ethanol (20 mL) was added hydrazine (228.17 mg, 7.12 mmol) at 20 °C. The mixture was stirred at 50 °C for 1 h, then cooled and purified by RP-HPLC to give the desired compound (383.0 mg, 33.51% yield) as a white solid. MS (ESI): m / z = 320.2 [M+H] +

[0194] Example A.6 6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane; 2,2,2-trifluoroacetic acid [ka] To a solution of 6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (1690 mg, 5.11 mmol) in dichloromethane (15 mL) was added TFA (5.82 g, 3.93 mL, 51.1 mmol), and the reaction mixture was stirred at room temperature for 18 hours. Volatiles were removed in vacuo to give 3340 mg of the crude title compound as a colorless viscous oil (purity approximately 50%; major contaminant excess TFA), which was used without further purification. MS (ESI): m / z = 215.2 [M+H] +

[0195] Step a) 6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester To a solution of 6-methylsulfonyloxy-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (2.7 g, 8.82 mmol) in N,N-dimethylformamide (36 mL) was added 3-(difluoromethyl)-1H-1,2,4-triazole (1000 mg, 8.4 mmol) and cesium carbonate (2.74 g, 8.4 mmol), and the reaction mixture was stirred at 90 °C for 18 h. The volatiles were removed in vacuo, and the crude residue was partitioned between ethyl acetate and 1 M aqueous Na2CO3, and the organic phase was collected. The aqueous phase was back-extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and evaporated to dryness to give a residue that was purified by flash chromatography (eluent mixture of heptane and ethyl acetate (10%-80%)) to give the title compound as a white solid. MS (ESI): m / z = 315.2 [M+H] + NOTE: A minor amount of an alternative regioisomer was also isolated. The regiochemistry was confirmed by NMR analysis.

[0196] Example B.34 5-(2-Azaspiro[3.3]heptan-6-ylmethyl)-3-(trifluoromethyl)-1,2,4-thiadiazole; 4-Methylbenzenesulfonic acid [ka] A mixture of p-toluenesulfonic acid (7.1 g, 41.2 mmol) and tert-butyl 6-[[3-(trifluoromethyl)-1,2,4-thiadiazol-5-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (6.51 g, 17.9 mmol) in EtOAc (100 mL) was stirred at 25 °C for 48 h. The reaction mixture was concentrated and crystallized from MTBE to give the title compound (7753 mg, 12.8 mmol, 71.2% yield) as a pale yellow solid. MS (ESI): m / z = 264.0 [M-TsOH+H] +

[0197] Step a) tert-butyl 6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-2-azaspiro[3.3]heptane-2-carboxylate A mixture of 2,2,6,6-tetramethylpiperidine (95.9 mL, 568 mmol) in THF (750 mL) was cooled to -30 °C under a N atmosphere. n-BuLi (227 mL, 568 mmol) was added dropwise, and the reaction mixture was stirred at the same temperature for 30 minutes. Next, the reaction mixture was cooled to -60 °C, and a solution of 4,4,5,5-tetramethyl-2-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl]-1,3,2-dioxaborolane (136 g, 506 mmol) in THF (750 mL) was added dropwise. After stirring for 30 minutes, a solution of tert-butyl 6-oxo-2-azaspiro[3.3]heptane-2-carboxylate (100 g, 473 mmol) in THF (300 mL) was added dropwise at -60 °C. The reaction mixture was slowly warmed to 25° C. and stirred at 25° C. for 12 h. HO (80 mL) was slowly added to the mixture, which was then purified with an additional batch of equal size by silica gel column (PE / EA=1:0 to 3:1 gradient) to give the title compound as a white solid (220 g, 656 mmol, approximately 69% yield per batch), which was 1 Confirmed by H NMR (400 MHz, chloroform-d) δ = 5.21-5.16 (m, 1H), 3.99-3.89 (m, 4H), 3.13-2.90 (m, 4H), 1.46-1.41 (m, 9H), 1.26-1.20 ppm (m, 13H).

[0198] Step b) tert-butyl 6-[[3-(trifluoromethyl)-1,2,4-thiadiazol-5-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate 5-Bromo-3-(trifluoromethyl)-1,2,4-thiadiazole (CAS: 1781783-65-0) (7.0 g, 30.0 mmol), tert-butyl 6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-2-azaspiro[3.3]heptane-2-carboxylate (8.5 g, 25.4 mmol), 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (4.14 g, 5.07 mmol), and potassium carbonate (7.01 g, 50.7 mmol) were dissolved in 1,4-dioxane (71 mL) and water (12.5 mL). The reaction mixture was heated to 90° C. under argon for 18 hours. The reaction mixture was concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water. The organic layer was washed with brine. The extract was dried over sodium sulfate, filtered through a thin layer of silica gel, and evaporated. The crude product was purified by flash chromatography (hexane / ethyl acetate 0-35%) to give tert-butyl 6-[[3-(trifluoromethyl)-1,2,4-thiadiazol-5-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate (6.5 g, 18.0 mmol, 70.9% yield) as a gray solid. MS (ESI): m / z = 360.0 [MH] - .

[0199] Step c) tert-butyl 6-[[3-(trifluoromethyl)-1,2,4-thiadiazol-5-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate A mixture of tert-butyl 6-[[3-(trifluoromethyl)-1,2,4-thiadiazol-5-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate (6.5 g, 18.0 mmol) and Pd / C 10% (574 mg, 0.54 mmol) in EtOAc (120 mL) was stirred in an autoclave under 30 bar H2 for 24 h. The reaction mixture was then filtered and concentrated to give the title compound (6.51 g, 17.9 mmol, 99.6% yield) as a colorless oil. MS (ESI): m / z = 362.2 [MH] - .

[0200] As in Example B.34, the following building blocks were prepared using the relevant (hetero)aryl bromide or iodide building blocks in the Suzuki coupling in step b. In some cases, alternative salts (e.g., trifluoroacetate, ditosylate, hydrochloride) were also used. Further building block substitutions can be made to introduce different spiro ring systems; for example, in Example B.353, tert-butyl 7-oxo-2-azaspiro[3.3]nonane-2-carboxylate (CAS: 1363381-22-9) was used instead of tert-butyl 6-oxo-2-azaspiro[3.5]heptane-2-carboxylate in step a). In some cases, the synthesis was designed to include the removal of an additional Br group in the hydrogenation step. [Table 3] TIFF2025536386000143.tif253170 TIFF2025536386000144.tif236170 TIFF2025536386000145.tif248170 TIFF2025536386000146.tif214170 TIFF2025536386000147.tif197170

[0201] Example B.32 6-[[4-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane; 4-Methylbenzenesulfonic acid [ka] A solution of tert-butyl 6-[[4-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (675 mg, 1.95 mmol) and p-toluenesulfonic acid (404 mg, 2.35 mmol) in EtOAc (6 mL) was stirred at 80 °C for 12 hours. The mixture was concentrated in vacuo to give a residue. Deionized water was added to the residue, and the mixture was lyophilized to give the title compound (794 mg, 96% yield) as a white solid. MS (ESI): m / z = 246.2 [M-TsOH+H] +

[0202] Step a) tert-butyl 6-[[4-(trifluoromethyl)pyrazol-1-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of 4-(trifluoromethyl)-1H-pyrazole (2435 mg, 17.9 mmol), tert-butyl 6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-2-azaspiro[3.3]heptane-2-carboxylate (Example B.34, step a)) (2000 mg, 5.97 mmol), and pyridine (1.45 mL, 17.9 mmol) in DMSO (80 mL) was added copper diacetate (2380 mg, 11.9 mmol) under an O atmosphere, followed by stirring at 100 °C for 12 hours under O (balloon) conditions. The aqueous phase was extracted with ethyl acetate (200 mL × 3). The combined organic phase was washed with brine (200 mL × 3), dried over anhydrous NaSO, filtered, and concentrated in vacuo. The residue was purified by flash silica gel chromatography (eluent: 0-30% ethyl acetate / petroleum ether) to give the crude product, which was purified by reverse-phase HPLC (0.1% FA) to give the title compound (640 mg, 31% yield) as a brown solid. MS (ESI): m / z = 288.1 [M-tBu+H] +

[0203] Step b) tert-butyl 6-[[4-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[[4-(trifluoromethyl)pyrazol-1-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate (690 mg, 2.01 mmol) in 7 mL of EtOAc was added wet Pd / C (230 mg, 0.200 mmol), and the mixture was stirred at 25 °C under a H atmosphere (balloon) for 2 h. The mixture was then filtered, and the filtrate was concentrated to give the title compound (690 mg, 99% yield) as a yellow solid. MS (ESI): m / z = 346.1 [M+H] +

[0204] Analogously to Example B.32, the (hetero)aryl building blocks involved in the Chan Lam-type coupling in step 1 were used to generate the following building blocks. In some cases, alternative salts (e.g., trifluoroacetate, ditosylate, hydrochloride) were also used. [Table 4]

[0205] Example B.347 5-(2,6-Diazaspiro[3.3]heptan-2-ylmethyl)-2-(trifluoromethyl)thiazole; 4-Methylbenzenesulfonic acid [ka] To a solution of tert-butyl 6-[[2-(trifluoromethyl)thiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptane-2-carboxylate (2000 mg, 5.5 mmol) in EtOAc (20 mL), p-toluenesulfonic acid monohydrate (3141 mg, 16.5 mmol, 3.0 equiv.) was added and stirred at 25 °C for 18 h. The reaction mixture was filtered, and the precipitate was washed with ether to give the title compound (2950.0 mg, 4.85 mmol, 88.2% yield) as a white solid. MS (ESI): m / z = 264.0 [M-TsOH+H] +

[0206] Step a) tert-butyl 6-[[2-(trifluoromethyl)thiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 2,6-diazaspiro[3.3]heptane-2-carboxylate hydrochloride (2526 mg, 10.8 mmol) and 2-(trifluoromethyl)thiazole-5-carbaldehyde (CAS: 903130-38-1) (1500 mg, 8.28 mmol) in DCE (30 mL) was added acetic acid (1.28 mL, 22.4 mmol). After stirring for 10 min, sodium triacetoxyborohydride (3686 mg, 17.4 mmol) was added, and the resulting mixture was stirred at room temperature overnight. The organic layer was washed with aqueous sodium bicarbonate, evaporated, and purified by flash chromatography (0–80% acetonitrile in chloroform) to give the title compound (2000 mg, 5.5 mmol, 66.5% yield) as a light brown solid. MS (ESI): m / z = 364.0 [M+H] + .

[0207] As in Example B.347, the following components were produced using the relevant components in step a): [Table 5] TIFF2025536386000152.tif255170 TIFF2025536386000153.tif249170 TIFF2025536386000154.tif217170 TIFF2025536386000155.tif249170 TIFF2025536386000156.tif178170 TIFF2025536386000157.tif249170 TIFF2025536386000158.tif249170 TIFF2025536386000159.tif254170 TIFF2025536386000160.tif245170 TIFF2025536386000161.tif245170 TIFF2025536386000162.tif245170 TIFF2025536386000163.tif245170 TIFF2025536386000164.tif245170 TIFF2025536386000165.tif217170 TIFF2025536386000166.tif240170 TIFF2025536386000167.tif249170 TIFF2025536386000168.tif240170 TIFF2025536386000169.tif254170 TIFF2025536386000170.tif249170 TIFF2025536386000171.tif240170 TIFF2025536386000172.tif233170 TIFF2025536386000173.tif233170 TIFF2025536386000174.tif233170 TIFF2025536386000175.tif121170

[0208] Example B.360 3-Cyclopropyl-5-(2,6-diazaspiro[3.3]heptan-2-ylmethyl)-1,2,4 thiadiazole; 4-Methylbenzenesulfonic acid [ka] To a solution of tert-butyl 6-[(3-cyclopropyl-1,2,4-thiadiazol-5-yl)methyl]-2,6-diazaspiro[3.3]heptane-2-carboxylate (558 mg, 1.66 mmol) in ACN (5 mL) was added p-toluenesulfonic acid monohydrate (789 mg, 4.15 mmol). The mixture was heated at 50 °C for 10 h. The mixture was cooled, and the precipitated solid was filtered, washed with EtOAc, and dried to give the title compound (844 mg, 1.45 mmol, 83% yield) as a white solid. MS (ESI): m / z = 237.0 [M+H] +

[0209] Step a) tert-butyl 6-[(3-cyclopropyl-1,2,4-thiadiazol-5-yl)methyl]-2,6-diazaspiro[3.3]heptane-2-carboxylate To a suspension of 5-(chloromethyl)-3-cyclopropyl-1,2,4-thiadiazole (CAS: 2090447-99-5) (521 mg, 2.98 mmol), tert-butyl 2,6-diazaspiro[3.3]heptane-2-carboxylate hydrochloride (700 mg, 2.98 mmol) in DCM (25 mL) was added diisopropylethylamine (2.6 mL, 14.9 mmol). The resulting mixture was stirred at room temperature for 16 hours and evaporated. The residue was purified by HPLC to give the title compound (558 mg, 1.66 mmol, 53.4% ​​yield) as a pale yellow solid. MS (ESI): m / z = 337.0 [M+H]

[0210] As in Example B.360, the following building blocks were prepared using relevant commercially available building blocks in step b). In the case of 4,6 or 4,5 spirocyclic systems, 2,7-diazaspiro[3.5]nonane-2-carboxylic acid tert-butyl ester and tert-butyl 2,6-diazaspiro[3.4]octane-2-carboxylate can be used instead of 2,6-diazaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester, respectively. In some cases, CsCO was used instead of KCO. In some cases, alternative salts of commercially available spirocyclic amine building blocks were used (e.g., hydrochlorides). [Table 6] TIFF2025536386000178.tif213170 TIFF2025536386000179.tif208170 TIFF2025536386000180.tif230170 TIFF2025536386000181.tif165170

[0211] Example B.311 6-[[5-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane; 4-Methylbenzenesulfonic acid [ka] To a solution of tert-butyl 6-[[5-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (200 mg, 0.58 mmol) in 2 mL of EtOAc, p-toluenesulfonic acid (110 mg, 0.64 mmol) was added and stirred at 80° C. for 12 hours. The reaction mixture was filtered and concentrated under reduced pressure to give the title compound (230 mg, 0.55 mmol, 95% yield) as a yellow oil. MS (ESI): m / z=246.1 [M+H] + .

[0212] Step a) tert-butyl 6-[[5-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate tert-Butyl 6-(hydroxymethyl)-2-azaspiro[3.3]heptane-2-carboxylate (CAS: To a mixture of 1363381-93-4 (10.0 g, 44.0 mmol), 5-(trifluoromethyl)-1H-pyrazole (5.99 g, 44.0 mmol), and triphenylphosphine (14.4 g, 55.0 mmol) in THF (100 mL) was added diisopropyl azodicarboxylate (10.4 mL, 52.8 mmol) at 0 °C, and the reaction mixture was then stirred at 20 °C under N for 12 hours. The reaction mixture was diluted with 100 mL and extracted with 300 mL of EtOAc (100 mL × 3). The combined organic layers were washed with saturated aqueous NaCl (50 mL), dried over NaSO, filtered, and concentrated under reduced pressure to give a residue. The residue was purified by normal-phase preparative HPLC to give the title compound (3.7 g, 10.7 mmol, 24.4% yield) as a yellow solid. MS (ESI): m / z = 346.1 [M+H] +

[0213] Analogously to Example B.311, the following components were produced using the relevant commercially available components in step a): [Table 7]

[0214] Example B.317 2-(2-Azaspiro[3.3]heptan-6-ylmethyl)-5-[1-(trifluoromethyl)cyclopropyl]-1,3,4 oxadiazole; 4-Methylbenzenesulfonic acid [ka] To a solution of 6-[[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (3.22 g, 8.31 mmol) in isopropyl acetate (163 mL) was added p-toluenesulfonic acid monohydrate (1.9 g, 9.97 mmol). The mixture was stirred at 85 °C for 4 h. The reaction mixture was concentrated in vacuo. EtO (100 mL) was added (partial crystallization began overnight). The mixture was concentrated under reduced pressure to give the title compound (4.25 g, 45%) as a white solid. MS (ESI): m / z = 288.0 [M+H] +

[0215] Step a) 6-(2-hydrazino-2-keto-ethyl)-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester To a solution of 2-(2-tert-butoxycarbonyl-2-azaspiro[3.3]heptan-6-yl)acetic acid (CAS: 1251002-39-7) (2.5 g, 9.79 mmol) in tetrahydrofuran (30 mL) was added CDI (1.75 g, 10.8 mmol). The mixture was stirred at 70 °C for 1.5 h. The RM was cooled to 0 °C, and hydrazine monohydrate (1.47 g, 1.42 mL, 29.4 mmol) was added, and the mixture was stirred at room temperature for 30 min. The reaction mixture was poured into 2:1 EtOAc / THF, washed with water and brine, dried over Na SO , and concentrated in vacuo to give the title compound (3.85 g, 99%) as a white solid. MS (ESI): m / z = 214.1 [M+H-C H ] +

[0216] Step b) 6-[2-keto-2-[N'-[1-(trifluoromethyl)cyclopropanecarbonyl]hydrazino]ethyl]-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester 1-(Trifluoromethyl)cyclopropanecarboxylic acid (CAS: To a solution of 277756-46-4 (1.5 g, 9.72 mmol) in dichloromethane (30 mL) was added 1-chloro-N,N,2-trimethylpropenamine (1.56 g, 1.54 mL, 11.7 mmol). The mixture was stirred at room temperature for 2 hours. This acid chloride solution was added dropwise to a solution of 6-(2-hydrazino-2-keto-ethyl)-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (3.85 g, 9.72 mmol) and DIEA (2.51 g, 3.4 mL, 19.4 mmol) in tetrahydrofuran (20 mL) at room temperature. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into 2:1 EtOAc / THF and washed with water and brine. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 80 g, 0% to 5% methanol in CH2Cl2) to give the title compound (3.49 g, 84.14%) as a white solid. MS (ESI): m / z = 350.1 [M+H-C4H8] +

[0217] Step c) 6-[[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester To a solution of 6-[2-keto-2-[N'-[1-(trifluoromethyl)cyclopropanecarbonyl]hydrazino]ethyl]-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (3.49 g, 8.61 mmol) in tetrahydrofuran (40 mL) was added Burgess reagent (4.1 g, 17.2 mmol). The mixture was stirred at 60 °C for 1 h. The reaction mixture was poured into EtOAc / THF 3:1 and washed with water and brine. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 80 g, 0% to 5% methanol in CHCl) to give 6-[[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (3.22 g, 92%) as a white solid. MS (ESI): m / z = 388.2 [M+H] + .

[0218] Example P.50 1-(2-Azaspiro[3.3]heptan-6-ylmethyl)-4-(trifluoromethyl)pyridin-2-one; 4-Methylbenzenesulfonic acid [ka] To a solution of tert-butyl 6-[[4-(trifluoromethyl)triazol-2-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (2.5 g, 7.2 mmol) in 100 mL of EtOAc was added p-toluenesulfonic acid monohydrate (4.12 g, 21.6 mmol). The reaction mixture was stirred at 25 °C for 18 h, filtered, and washed with diethyl ether to give the title compound (3.63 g, 81% yield) as a white powder. MS (ESI): m / z = 247.2 [M+H] + .

[0219] Step a) tert-butyl 6-(methylsulfonyloxymethyl)-2-azaspiro[3.3]heptane-2-carboxylate To a stirred solution of tert-butyl 6-(hydroxymethyl)-2-azaspiro[3.3]heptane-2-carboxylate (CAS: 1363381-93-4) (14.9 g, 65.7 mmol) in DCM (299 mL) was added triethylamine (13.7 mL, 98.6 mmol), the reaction mixture was cooled to 0 °C, methanesulfonyl chloride (6.1 mL, 78.9 mmol) was added dropwise, and the reaction mixture was stirred at room temperature for 4 h. The reaction mixture was diluted with water, extracted with DCM, washed with water, brine, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to give the title compound (19.8 g, 64.8 mmol, 93.7% yield) as a pale yellow solid. MS (ESI): m / z = 250.0 [M-Bu + H] + .

[0220] Step b) tert-butyl 6-[[4-(trifluoromethyl)triazol-2-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate To a mixture of 4-(trifluoromethyl)-1H-triazole (2.69 g, 19.7 mmol) and lithium bromide (3.41 g, 39.3 mmol) in acetonitrile (300 mL) was added tert-butyl 6-(methylsulfonyloxymethyl)-2-azaspiro[3.3]heptane-2-carboxylate (6.0 g, 19.65 mmol, 1 equiv., CAS 2740574-92-7). The reaction mixture was stirred at 50 °C for 18 h, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (silica gel, 220 g, 0% to 100% MTBE in heptane) to give the title compound (2.5 g, 36% yield) as a pale yellow solid. MS (ESI): m / z = 247.0 [M+H-Boc] + .

[0221] The following building blocks were prepared using the relevant commercially available building blocks in step a) analogously to Example P.50: In some cases, sodium iodide was used in place of lithium bromide in step a). [Table 8]

[0222] Example P.62 6-[[3-(difluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptane;2,2,2-trifluoroacetic acid [ka] To a solution of tert-butyl 6-[[5-(difluoromethyl)-2-(2-trimethylsilylethoxymethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (6 g, 13.1 mmol) in dichloromethane (40 mL) was added 2,2,2-trifluoroacetic acid (20 mL) at 0° C. The mixture was stirred at 20° C. for 16 hours. The reaction mixture was concentrated in vacuo. The residue was purified by preparative HPLC to give the title compound (3.94 g, 87% yield) as a white solid. MS (ESI): m / z=228.2 [M+H] + .

[0223] Step a) tert-butyl 6-[[5-(difluoromethyl)-2-(2-trimethylsilylethoxymethyl)pyrazol-3-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate 2-[[5-Bromo-3-(difluoromethyl)pyrazol-1-yl]methoxy]ethyl-trimethyl-silane (5.3 g, 16.2 mmol, CAS 2416163-95-4), tert-butyl 6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-2-azaspiro[3.3]heptane-2-carboxylate (5.97 g, 17.8 mmol, CAS 2416163-95-4), To a mixture of (2,4-dien-1-yl)phosphane (4.47 g, 32.4 mmol) and potassium carbonate (4.47 g, 32.4 mmol) in 1,4-dioxane (50 mL) and water (5 mL) under N was added cyclopenta-2,4-dien-1-yl(diphenyl)phosphane; dichloromethane; dichloropalladium; and iron(2+) (1.32 g, 1.62 mmol, 0.1 equiv., CAS 95464-05-4). The mixture was stirred at 100 °C under N for 2 h. The reaction mixture was poured into water (500 mL). The aqueous layer was extracted with EtOAc (300 mL × 2). The organic phase was washed with brine (600 mL), dried over anhydrous NaSO, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 100 / 1 to 1 / 1) to give the title compound (6.1 g, 13.4 mmol, 79% yield) as a light yellow solid. MS (ESI): m / z = 456.3 [M+H] + .

[0224] Step b) tert-butyl 6-[[5-(difluoromethyl)-2-(2-trimethylsilylethoxymethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[[5-(difluoromethyl)-2-(2-trimethylsilylethoxymethyl)pyrazol-3-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate (7 g, 15.4 mmol) in 100 mL of EtOAc was added Pd / C 10% (2 g, 4.61 mmol, 0.3 equiv.) under a N atmosphere. The mixture was stirred at 25 °C under a H atmosphere (15 PSI) for 0.5 h. The reaction mixture was filtered and concentrated under reduced pressure to give tert-butyl 6-[[5-(difluoromethyl)-2-(2-trimethylsilylethoxymethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (6 g, 85% yield) as a colorless oil.

[0225] Example B.376 6-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]oxy-2-azaspiro[3.3]heptane;2,2,2-trifluoroacetic acid [ka] To a solution of tert-butyl 6-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]oxy-2-azaspiro[3.3]heptane-2-carboxylate (315 mg, 0.87 mmol) in DCM (10 mL) cooled to 0 °C, trifluoroacetic acid (0.4 mL, 5.23 mmol) was added. The resulting mixture was stirred at 20 °C for 10 h and concentrated. The residue was triturated with EtO, and the precipitated solid was filtered and dried to give the title compound (254 mg, 0.68 mmol, 75.1% yield) as a white solid. MS m / z: 262.2 [M-TFA+H] +

[0226] Step a) tert-butyl 6-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]oxy-2-azaspiro[3.3]heptane-2-carboxylate A solution of tert-butyl 6-hydroxy-2-azaspiro[3.3]heptane-2-carboxylate (1000 mg, 4.69 mmol) and 1-methyl-3-(trifluoromethyl)pyrazol-4-ol (CAS: 172834-79-6) (857 mg, 5.16 mmol) in THF (20 mL) was cooled to 0 °C, and triphenylphosphine (1599 mg, 6.1 mmol) was added. A solution of diisopropyl azodicarboxylate (1.2 mL, 6.1 mmol) in THF (2 mL) was added dropwise under Ar. The mixture was warmed to 20 °C and stirred for 24 h. The mixture was concentrated, and the residue was triturated with TBME. The precipitated solid was filtered, and the filtrate was concentrated. The residue was purified by FC (silica, DCM in TBME 0-100%) to give the title compound (315 mg, 0.87 mmol, 18.6% yield) as a white solid. MS m / z: 306.0 [M-C4H8+H] +

[0227] Analogously to Example B.376, the following building blocks were produced using relevant commercially available building blocks in step a): [Table 9]

[0228] Example B.349 3-(2-Azaspiro[3.3]heptan-6-ylmethyl)-5-(trifluoromethyl)-1,2,4-thiadiazole; 4-Methylbenzenesulfonic acid [ka] A mixture of tert-butyl 6-[[5-(trifluoromethyl)-1,2,4-thiadiazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (400 mg, 1.1 mmol) and TsOH (227 mg, 1.32 mmol) in EtOAc (5 mL) was stirred at 80 °C for 3 h. The reaction mixture was concentrated under reduced pressure and lyophilized to give the title compound (415 mg, 0.95 mmol, 85.3% yield) as a white solid. MS (ESI): m / z = 264.0 [M-TsOH+H] +

[0229] Step a) tert-Butyl 6-(cyanomethyl)-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-(methylsulfonyloxymethyl)-2-azaspiro[3.3]heptane-2-carboxylate (2740574-92-7) (5.0 g, 16.4 mmol) in DMSO (70 mL) was added potassium cyanide (2.45 g, 37.7 mmol) at room temperature. The resulting solution was stirred at 80 °C for 18 hours. The reaction was quenched with water (50 mL) and then extracted with TBME (3 × 100 mL). The organic layer was washed with brine, dried over Na SO , filtered, and concentrated under reduced pressure to give the title compound (3.4 g, 14.4 mmol, 83.6% yield) as a white solid. MS (ESI): m / z = 181.0 [M-CH + H] + .

[0230] Step b) tert-butyl 6-[2-(hydroxyamino)-2-imino-ethyl]-2-azaspiro[3.3]heptane-2-carboxylate To a mixture of hydroxylamine hydrochloride (2353 mg, 33.9 mmol) in ethanol (25 mL) was added TEA (3426 mg, 33.9 mmol) at 25 °C. After 1 h, tert-butyl 6-(cyanomethyl)-2-azaspiro[3.3]heptane-2-carboxylate (4000 mg, 16.9 mmol) was added to the above reaction mixture, and the reaction was then stirred at 50 °C for an additional 12 h. The reaction was concentrated under reduced pressure to give a residue. The residue was dissolved in water (50 mL) and extracted with ethyl acetate (50 mL × 3). The combined extracts were concentrated under reduced pressure to give the title compound (4.5 g, 16.7 mmol, 98.7% yield) as a colorless oil, which was used in the next step without further purification. MS (ESI): m / z = 270.1 [M+H] +

[0231] Step c) tert-butyl 6-(2-amino-2-imino-ethyl)-2-azaspiro[3.3]heptane-2-carboxylate; acetic acid To a solution of tert-butyl 6-[2-(hydroxyamino)-2-imino-ethyl]-2-azaspiro[3.3]heptane-2-carboxylate (4.5 g, 16.7 mmol) and AcO (2.56 g, 25.1 mmol) in acetic acid (20 mL) was added Pd / C (wet) (1.2 g) at 25 °C. The reaction was then stirred under a H atmosphere (H balloon) at 25 °C for 12 h. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give the crude title compound (5.2 g, 16.6 mmol, 99.3% yield) as a pale yellow oil. MS (ESI): m / z = 254.0 [M-AcOH + H] +

[0232] Step d) tert-butyl 6-[(5-amino-1,2,4-thiadiazol-3-yl)methyl]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-(2-amino-2-imino-ethyl)-2-azaspiro[3.3]heptane-2-carboxylate; acetic acid (3000 mg, 9.57 mmol) in water (30 mL) was added dropwise sodium hypochlorite (15.0 mL, 10.5 mmol) at 0 ° C. The mixture was then stirred at 20 ° C. for 1 hour, diluted with water, extracted with EtOAc (20 mL × 3), the combined organic phase was dried over Na SO and concentrated, the residue was dissolved in methanol (30 mL), potassium thiocyanate (1023 mg, 10.5 mmol) was added at 0 ° C. The solution was then stirred at 20 ° C. for 11 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to obtain a residue. The residue was purified by column chromatography on silica (ethyl acetate:petroleum ether 0-80%) and concentrated under reduced pressure to give the title compound (1400 mg, 4.51 mmol, 47.1% yield) as a brown solid. MS (ESI): m / z = 311.0 [M+H] +

[0233] Step e) tert-butyl 6-[(5-iodo-1,2,4-thiadiazol-3-yl)methyl]-2-azaspiro[3.3]heptane-2-carboxylate To a mixture of tert-butyl 6-[(5-amino-1,2,4-thiadiazol-3-yl)methyl]-2-azaspiro[3.3]heptane-2-carboxylate (1400 mg, 4.51 mmol) and CuI (1718 mg, 9.02 mmol) in MeCN (50 mL) was added a solution of tert-butyl nitrite (930 mg, 9.02 mmol, 2.0 equiv.) in MeCN (5 mL) at 25 °C, and the reaction was then stirred at 70 °C under a N atmosphere for 12 h. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by column chromatography on silica (ethyl acetate:petroleum ether 0-40%) and concentrated under reduced pressure to give the title compound (900 mg, 2.14 mmol, 47.4% yield) as a yellow solid. MS (ESI): m / z = 421.9 [M+H] +

[0234] Step f) tert-butyl 6-[[5-(trifluoromethyl)-1,2,4-thiadiazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate A mixture of tert-butyl 6-[(5-iodo-1,2,4-thiadiazol-3-yl)methyl]-2-azaspiro[3.3]heptane-2-carboxylate (890 mg, 2.11 mmol), diphenyl(trifluoromethyl)sulfonium trifluoromethanesulfonate (1025 mg, 2.54 mmol), and Cu (1207 mg, 6.34 mmol) in DMF (8 mL) was stirred at 60 °C under a N atmosphere for 12 h. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by reverse flash (FA conditions; MeCN:HO = 0-70%) and lyophilized to give the residue. This residue was purified by silica column chromatography (ethyl acetate:petroleum ether = 0-30%) and concentrated under reduced pressure to give the title compound (400 mg, 1.1 mmol, 52.1% yield) as a colorless oil. MS (ESI): m / z = 307.9 [M-C4H8+H] +

[0235] Example B.377 6-[[4-[1-(trifluoromethyl)cyclopropyl]pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane; 4-Methylbenzenesulfonic acid [ka] A solution of tert-butyl 6-[[4-[1-(trifluoromethyl)cyclopropyl]pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (400 mg, 1.04 mmol) and p-toluenesulfonic acid (214 mg, 1.25 mmol) in 8 mL of EtOAc was stirred at 80° C. for 12 hours. The reaction mixture was concentrated and lyophilized to give the title compound (467 mg, 1.02 mmol, 91% yield) as a light brown solid. MS (ESI): m / z=286.2 [M+H] +

[0236] Step a) tert-butyl 6-[(4-bromopyrazol-1-yl)methylene]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of 4-bromopyrazole (2000 mg, 13.6 mmol) in DCE (40 mL) was added tert-butyl 6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-2-azaspiro[3.3]heptane-2-carboxylate (6840 mg, 20.4 mmol), pyridine (2153 mg, 27.2 mmol), boric acid (841 mg, 13.6 mmol), and Cu(OAc) (3670 mg, 18.4 mmol). The mixture was stirred at 70 °C under O for 12 h. The reaction mixture was purified by preparative HPLC and lyophilized. The residue was triturated in petroleum ether (10 mL) and stirred for 10 min. The solid was collected by filtration to give the title compound (2867 mg, 8.09 mmol, 59% yield) as an off-white solid. MS (ESI): m / z = 298.1 [M+H] +

[0237] Step b) tert-butyl 6-[(4-bromopyrazol-1-yl)methyl]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[(4-bromopyrazol-1-yl)methylene]-2-azaspiro[3.3]heptane-2-carboxylate (2300 mg, 6.49 mmol) in 25 mL of EtOAc was added PtO (920 mg, 4.05 mmol) under N at 20 °C, and the mixture was then stirred under a H atmosphere (balloon) at 20 °C for 1 h. The precipitate was filtered, and the filtrate was dried under reduced pressure. The residue was purified by column chromatography (hexane / EtOAc, 1:1) to afford the title compound (2200 mg, 6.18 mmol, 95% yield) as a pale yellow solid. MS (ESI): m / z = 302.0 [M-C4H8+H] +

[0238] Step c) tert-butyl 6-[[4-[1-(trifluoromethyl)vinyl]pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[(4-bromopyrazol-1-yl)methyl]-2-azaspiro[3.3]heptane-2-carboxylate (1700 mg, 4.77 mmol) in 1,4-dioxane (20 mL) and water (4 mL) was added 1-(trifluoromethyl)vinylboronic acid hexylene glycol ester (1270 mg, 5.73 mmol), KCO (1980 mg, 14.3 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride (390 mg, 0.48 mmol) under N. The mixture was stirred at 80 °C for 12 h under N. The precipitate was filtered, and the filtrate was dried under reduced pressure. The residue was purified by column chromatography (PE / EA, 0-60%). The reaction mixture was purified by preparative HPLC and lyophilized to give the title compound (1134.0 mg, 3.05 mmol, 64% yield) as a light brown solid. MS (ESI): m / z=372.1 [M+H] +

[0239] Step d) tert-butyl 6-[[4-[1-(trifluoromethyl)cyclopropyl]pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[[4-[1-(trifluoromethyl)vinyl]pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (1000 mg, 2.69 mmol) in THF (20 mL) was added diphenyl(methyl)sulfonium tetrafluoroborate (1008 mg, 3.5 mmol). The suspension was cooled to 0 °C, and NaHMDS / THF (1 M) (10.8 mL, 10.8 mmol) was added dropwise. The reaction mixture was warmed to 20 °C and stirred for 12 h. The reaction mixture was purified by preparative HPLC and lyophilized to give the title compound (432 mg, 1.12 mmol, 42% yield) as a pale yellow solid. MS (ESI): m / z = 386.1 [M+H] +

[0240] Similar to Example B.377, the following components were produced using relevant commercially available components: [Table 10]

[0241] Example B.379 6-[[1-cyclopropyl-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptane; 4-Methylbenzenesulfonic acid [ka] To a mixture of tert-butyl 6-[[1-cyclopropyl-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (790 mg, 2.05 mmol) in 8 mL of EtOAc was added p-toluenesulfonic acid (388 mg, 2.25 mmol) at 25 °C, and the reaction mixture was stirred at 80 °C for 12 hours. The reaction mixture was concentrated under reduced pressure to give a residue. 20 mL of deionized water and 2 mL of ACN were added to the residue, which was then lyophilized to give the title compound (811 mg, 1.77 mmol, 85% yield) as a yellow oil. MS (ESI): m / z = 286.1 [M-TsOH+H] +

[0242] Step a) tert-butyl 6-[[5-(trifluoromethyl)-1H-pyrazol-4-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-2-azaspiro[3.3]heptane-2-carboxylate (5009 mg, 14.9 mmol), 4-bromo-5-(trifluoromethyl)-1H-pyrazole (2920 mg, 13.6 mmol) in 1,4-dioxane (73 mL), water (14.6 mL) was added potassium carbonate (3750 mg, 27.2 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (554 mg, 0.68 mmol) at 20° C., and the reaction was then stirred at 100° C. under N for 12 hours. The reaction mixture was filtered and concentrated under reduced pressure to give a residue that was purified by flash silica gel chromatography (eluent: 0-40% ethyl acetate / petroleum ether) to give the crude product, which was further purified by flash silica gel chromatography (eluent: 0-40% ethyl acetate / petroleum ether) to give the title compound (790 mg, 2.3 mmol, 17% yield) as a yellow oil. MS (ESI): m / z = 288.0 [M-C4H8+H] + .

[0243] Step b) tert-butyl 6-[[1-cyclopropyl-3-(trifluoromethyl)pyrazol-4-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate To a mixture of tert-butyl 6-[[5-(trifluoromethyl)-1H-pyrazol-4-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate (600 mg, 1.75 mmol), cyclopropylboronic acid (600 mg, 6.99 mmol) in DCE (6 mL) was added pyridine (0.42 mL, 5.24 mmol), boric acid (108 mg, 1.75 mmol), and copper diacetate (698 mg, 3.5 mmol) at 20 °C, and the reaction mixture was stirred at 100 °C under O (balloon) for 16 h. The reaction mixture was filtered, diluted with 50 mL of water, and extracted with 150 mL of EtOAc (50 mL × 3). The combined organic layers were washed with brine (40 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to give a residue that was purified by silica gel chromatography (0-28% ethyl acetate / petroleum ether) to give the title compound (350 mg, 0.91 mmol, 52%) as a colorless oil. MS (ESI): m / z = 328.0 [M-C4H8+H] + .

[0244] Step c) tert-butyl 6-[[1-cyclopropyl-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate To a mixture of tert-butyl 6-[[1-cyclopropyl-3-(trifluoromethyl)pyrazol-4-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate (720 mg, 1.88 mmol) in 15 mL of EtOAc was added Pd / C (wet, 216 mg, 10%) at 25 °C, and the reaction mixture was stirred under H (15 Psi) at 25 °C for 0.5 h. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give the title compound (640 mg, 1.66 mmol, 88.4% yield) as a colorless oil. MS (ESI): m / z = 330.0 [M-CH + H] + .

[0245] Example B.381 6-[[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane; 4-Methylbenzenesulfonic acid [ka] A mixture of tert-butyl 6-[[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (3.8 g, 10.57 mmol, 1.0 equiv.) and p-toluenesulfonic acid (4.55 g, 26.43 mmol, 2.5 equiv.) in EtOAc (70 mL) was stirred at 25 °C for 24 h. The reaction mixture was then concentrated and crystallized from MTBE to give 4-methylbenzenesulfonic acid; 6-[[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane (3940 mg, 9.13 mmol, 86% yield) as a white solid. MS (ESI): m / z = 260.2 [M+H] +

[0246] Step a) tert-butyl 6-[[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-(hydroxymethyl)-2-azaspiro[3.3]heptane-2-carboxylate (1000 mg, 4.4 mmol) in toluene (20 mL) was added 3-methyl-5-(trifluoromethyl)-1H-pyrazole (CAS: 10010-93-2) (660 mg, 4.4 mmol) and (cyanomethylene)tributylphosphorane (1590 mg, 6.6 mmol). The reaction mixture was stirred at 100 °C under a N atmosphere for 12 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by preparative HPLC and lyophilized to give the title compound (485 mg, 1.35 mmol, 31% yield) as a dark brown powder. MS (ESI): m / z = 304.0 [M+H] + Note: The regioisomeric tert-butyl 6-[[3-methyl-5-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (735 mg, 2.05 mmol, 46.5% yield) was also produced as a dark brown oil. MS (ESI): m / z = 304.0 [M+H] +

[0247] Example B.382 6-[[3-methyl-5-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane; 4-Methylbenzenesulfonic acid [ka] A mixture of tert-butyl 6-[[3-methyl-5-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (B.381, generated as the regioisomer in step a) (2.3 g, 6.4 mmol) and p-toluenesulfonic acid (2755 mg, 16.0 mmol) in 50 mL of EtOAc was stirred at 25 °C for 24 hours. The reaction mixture was then concentrated and crystallized from MTBE to give the title compound (1468 mg, 3.4 mmol, 53% yield) as a white solid. MS (ESI): m / z = 260.2 [M+H] +

[0248] Analogously to Examples B.381 / B.382, the following regioisomeric pairs of building blocks were generated using related commercially available building blocks. [Table 11]

[0249] Example B.390 6-(1-methylpyrazol-4-yl)oxy-2-azaspiro[3.3]heptane; 4-Methylbenzenesulfonic acid [ka] To a solution of tert-butyl 6-(1-methylpyrazol-4-yl)oxy-2-azaspiro[3.3]heptane-2-carboxylate (970 mg, 3.31 mmol) in EtOAc (20 mL) was added TsOH (968 mg, 5.62 mmol). The mixture was then stirred at 80° C. for 16 hours. The reaction mixture was concentrated under reduced pressure at 20° C. to give the crude product. Water (15 mL) was then added to the crude product. The solution was lyophilized to give the title compound (845 mg, 1.57 mmol, 47% yield) as a yellow gum. MS (ESI): m / z=194.2 [M-TsOH+H] +

[0250] Step a) tert-butyl 6-(1-methylpyrazol-4-yl)oxy-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-hydroxy-2-azaspiro[3.3]heptane-2-carboxylate (1087 mg, 5.1 mmol) and 1-methylpyrazol-4-ol (500 mg, 5.1 mmol) in toluene (25 mL), CMBP ((cyanomethylene)tributylphosphorane) (6150 mg, 25.5 mmol) was added under a N atmosphere, and the mixture was stirred at 110 °C for 16 h. The mixture was concentrated in vacuo to give a residue that was purified by flash silica gel chromatography (petroleum ether:ethyl acetate 2:1 to 1:1). The purified solution was concentrated in vacuo to give the title compound (1000 mg, 3.41 mmol, 67% yield) as a yellow solid. MS (ESI): m / z = 238.2 [M-CH + H] +

[0251] Example B.400 3-(2-Azaspiro[3.3]heptan-6-ylmethyl)-5-(trifluoromethyl)-1,2,4-oxadiazole; 4-Methylbenzenesulfonic acid [ka] A mixture of tert-butyl 6-[[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (350 mg, 1.01 mmol) and TsOH (208 mg, 1.21 mmol) in ethyl acetate (10 mL) was stirred at 80° C. for 12 hours. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was dissolved in MeCN (2.0 mL) and water (20.0 mL) and lyophilized to give the title compound (410 mg, 0.98 mmol, 91% yield) as a white solid. MS (ESI): m / z = 248.0 [M-TsOH+H] +

[0252] Step a) tert-butyl 6-[(2Z)-2-amino-2-hydroxyimino-ethyl]-2-azaspiro[3.3]heptane-2-carboxylate To a mixture of hydroxylamine hydrochloride (2353 mg, 33.9 mmol) in ethanol (25 mL) was added TEA (3426 mg, 33.9 mmol) at 25 °C. After 1 h, tert-butyl 6-(cyanomethyl)-2-azaspiro[3.3]heptane-2-carboxylate (B.349, step a)) (4000 mg, 16.9 mmol) was added to the reaction mixture, and the reaction was then stirred at 50 °C for an additional 12 h. The reaction was concentrated under reduced pressure to give a residue. The residue was dissolved in water (50 mL) and extracted with ethyl acetate (50 mL x 3). The combined extracts were concentrated under reduced pressure to give the title compound (4.5 g, 16.7 mmol, 99% yield) as a colorless oil, which was used in the next step without further purification. MS (ESI): m / z = 270.1 [M+H] +

[0253] Step b) tert-butyl 6-[[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[(2Z)-2-amino-2-hydroxyimino-ethyl]-2-azaspiro[3.3]heptane-2-carboxylate (800 mg, 2.97 mmol) in methanol (20 mL) was added NaOMe (MeOH solution) (1.19 mL, 5.94 mmol) and ethyl trifluoroacetate (2110 mg, 14.9 mmol) at 30 °C. The reaction was then stirred at 50 °C for 12 hours. The reaction was concentrated under reduced pressure to give a residue. The residue was dissolved in water (20 mL), and the reaction mixture was extracted with ethyl acetate (10 mL × 3), and the combined extracts were concentrated under reduced pressure to give a residue. The residue was purified by preparative HPLC and lyophilized to give the title compound (360.0 mg, 1.04 mmol, 34.9% yield) as a colorless oil. MS(ESI): m / z=292.0[M-C4H8+H] +

[0254] Example B.408 6-[[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptane; 4-Methylbenzenesulfonic acid [ka] To a mixture of tert-butyl 6-[[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (1.05 g, 2.46 mmol) in 10 mL of EtOAc was added p-toluenesulfonic acid (465 mg, 2.7 mmol) at 20° C., and the reaction mixture was then stirred at 80° C. for 12 hours. The reaction mixture was concentrated under reduced pressure to give a residue. 20 mL of deionized water and 2 mL of ACN were then added to the residue. The mixture was lyophilized to give the title compound (1224 mg, 2.45 mmol, 99% yield) as a pale yellow oil. MS (ESI): m / z=328.0 [M+H] + .

[0255] Step a) tert-butyl 6-[[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate To a mixture of tert-butyl 6-[[5-(trifluoromethyl)-1H-pyrazol-4-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate (B.379, step a) (2000 mg, 5.83 mmol) and cesium carbonate (5694 mg, 17.5 mmol) in DMF (20 mL) was added a solution of 2,2,2-trifluoroethyl trifluoromethanesulfonate (2704 mg, 11.7 mmol) in DMF (2 mL) at 0° C., and the mixture was stirred at 20° C. for 12 hours. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (100 mL × 3). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated in vacuo to give a residue that was purified by flash silica gel chromatography (eluent 0-28% ethyl acetate / petroleum ether) to give the title compound (1.1 g, 2.59 mmol, 44% yield) as a white solid. MS (ESI): m / z = 370.0 [M-C4H8+H] + .

[0256] Step b) tert-butyl 6-[[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate To a mixture of tert-butyl 6-[[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate (1000 mg, 2.35 mmol) in 10 mL of EtOAc was added Pd / C (300 mg, 10%, wet) at 20 °C, and the reaction mixture was stirred under H at 20 °C for 1 h. The reaction mixture was concentrated under reduced pressure to give tert-butyl 6-[[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (1.05 g, 2.46 mmol, 104% yield) as a colorless oil. MS (ESI): m / z = 372.0 [M-CH + H] + .

[0257] Example B.409 6-[(3-cyclopropyl-1H-pyrazol-5-yl)methyl]-2-azaspiro[3.3]heptane; 2,2,2-trifluoroacetic acid [ka] To a solution of 6-[(3-cyclopropyl-1H-pyrazol-5-yl)methyl]-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (180 mg, 567 μmol) in dichloromethane (2.44 mL) was added TFA (647 mg, 437 μL, 5.67 mmol), and the reaction mixture was stirred at room temperature for 18 hours. Volatiles were removed in vacuo to give 374 mg of the crude title compound, which was used without further purification and was approximately 50% pure with the major contaminant in excess of TFA. MS (ESI): m / z = 218.2 [M-TFA + H] + .

[0258] Step a) tert-butyl 6-(4-cyclopropyl-2,4-dioxo-butyl)-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-(2-ethoxy-2-oxo-ethyl)-2-azaspiro[3.3]heptane-2-carboxylate (CAS: 2173992-27-) (2000 mg, 7.06 mmol) in THF (20 mL) was added NaH (791 mg, 19.8 mmol) at 0 °C. After 0.5 h, cyclopropyl methyl ketone (594 mg, 7.06 mmol) was added at 0 °C. The mixture was stirred at 60 °C for 12 h. The reaction mixture was quenched at 25 °C by adding HO (10 mL), then diluted with HO (10 mL) and extracted with EtOAc (10 mL × 3). The combined organic layer was washed with saturated aqueous NaCl (10 mL × 3), dried over anhydrous NaSO, filtered, and concentrated under reduced pressure to give a residue. The residue was purified by preparative TLC (SiO, petroleum ether / ethyl acetate=3:1) to give the title compound (600 mg, 1.87 mmol, 26% yield) as a yellow oil. MS (ESI): m / z=266.2 [M-C4H8+H] + .

[0259] Step b) tert-butyl 6-[(5-cyclopropyl-1H-pyrazol-3-yl)methyl]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-(4-cyclopropyl-2,4-dioxo-butyl)-2-azaspiro[3.3]heptane-2-carboxylate (540 mg, 1.68 mmol) in ethanol (5 mL) was added hydrazine (108 mg, 3.36 mmol) at 20 °C, and the resulting mixture was stirred at 60 °C for 1 h. The filtrate was purified by preparative HPLC and lyophilized to give the title compound (458 mg, 1.44 mmol, 77% yield) as a colorless oil. MS (ESI): m / z = 262.1 [M-CH+H] + .

[0260] Example B.414 5-(2-Azaspiro[3.3]heptan-6-ylmethyl)-3-(trifluoromethyl)-1,2,4-oxadiazole; 4-Methylbenzenesulfonic acid [ka] To a solution of tert-butyl 6-[[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (118.0 mg, 0.34 mmol) in 2 mL of EtOAc, p-toluenesulfonic acid (70.2 mg, 0.41 mmol) was added at 80 °C and stirred for 12 hours. The mixture was concentrated under reduced pressure to give a residue. Deionized water was added to the residue, which was then lyophilized to give the title compound (125 mg, 0.3 mmol, 84% yield) as a white solid. MS (ESI): m / z = 248.1 [M-TsOH+H] +

[0261] Step a) tert-butyl 6-[[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-(2-ethoxy-2-oxo-ethyl)-2-azaspiro[3.3]heptane-2-carboxylate (CAS: 2173992-27-1) (300 mg, 1.06 mmol), 2,2,2-trifluoro-N'-hydroxy-acetamidine (CAS: 4314-35-6) in methanol (3 mL), a solution of sodium methoxide in MeOH (5 M) (0.42 mL, 2.12 mmol) was added at 25 ° C., and the mixture was then stirred at 60 ° C. for 12 hours. The residue was purified by preparative HPLC and lyophilized to give the title compound (120 mg, 0.35 mmol, 33% yield) as a yellow oil. 1 H NMR(400 MHz,chloroform-d)δ=3.96(s,2H),3.85(s,2H),3.06(d,J=7.6 Hz,2H),2.71(spt,J=7.9 Hz,1H),2.51-2.39(m,2H),2.07-1.95(m,2H),1.44(s,9H).MS(ESI):m / z=292.0[M-C4H8+H] +

[0262] Example B.415 6-[[2-(2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane; 4-Methylbenzenesulfonic acid [ka] A solution of p-toluenesulfonic acid (247 mg, 1.43 mmol) and tert-butyl 6-[[2-(2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (510 mg, 1.19 mmol) in EtOAc (5 mL) was stirred at 80 °C for 12 hours. The mixture was concentrated under reduced pressure to give a residue. Deionized water was added to the residue, and the mixture was lyophilized to give the title compound (550 mg, 1.1 mmol, 92.3% yield) as a colorless oil. MS (ESI): m / z = 328.0 [M-TsOH+H] +

[0263] Step a) tert-butyl 6-[[2-(2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[[5-(trifluoromethyl)-1H-pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (produced in the synthesis of P.7, step c) (1.5 g, 4.34 mmol) in THF (15 mL) was added NaH (261 mg, 6.51 mmol) at 0 °C for 0.5 h. Then, 2,2,2-trifluoroethyl trifluoromethanesulfonate (2016 mg, 8.69 mmol) was added at 20 °C, and the reaction was stirred for 12 h. The reaction was slowly quenched with ice and then extracted with EtOAc (20 mL × 3). The combined organic phase was washed with brine (20 mL × 3), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was purified by preparative HPLC and lyophilized to give the regioisomeric tert-butyl 6- [[1- (2,2,2-trifluoroethyl) -5- (trifluoromethyl) pyrazol-3-yl] methyl] -2-azaspiro [3.3] heptane-2-carboxylate (240.0 mg, 0.56 mmol, 12.93% yield) (crude) and tert-butyl 6- [[2- (2,2,2-trifluoroethyl) -5- (trifluoromethyl) pyrazol-3-yl] methyl] -2-azaspiro [3.3] heptane-2-carboxylate (800 mg, 1.87 mmol, 43.1% yield) (crude) as a yellow solid. The residue was purified by preparative HPLC to give the title compound (530 mg, 1.24 mmol, 66% yield) as a colorless oil. MS (ESI): m / z = 372.0 [M-C4H8+H] +

[0264] Example B.416 6-[[1-(2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane; 4-Methylbenzenesulfonic acid [ka] A solution of p-toluenesulfonic acid (43.5 mg, 0.25 mmol) and tert-butyl 6-[[1-(2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (the regioisomeric product of B.415, step a)) (90.0 mg, 0.21 mmol) in EtOAc (2 mL) was stirred at 80 °C for 12 hours. The mixture was concentrated under reduced pressure to give a residue. Deionized water was added to the residue, and the mixture was lyophilized to give 4-methylbenzenesulfonic acid; 6-[[1-(2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane (95.4 mg, 0.19 mmol, 88.31% yield) as an off-white solid. MS (ESI): m / z = 328.0 [M-TsOH + H] + ; 1 H NMR(400 MHz,DMSO-d6)δ=8.56-8.34(m,1H),7.47(d,J=8.1 Hz,3H),7.11(d,J=7.9 Hz,3H),6.85(s,1H),5.16(q,J=8.8 Hz,2H),4.00-3.92(m,2H),3.87-3.79(m,2H),2.64(d,J=7.3 Hz,2H),2.48-2.35(m,2H),2.34-2.30(m,1H),2.29(s,4H),1.95-1.86(m,2H)

[0265] Example B.443 6-[[3-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl]methyl]-2-azaspiro[3.3]heptane;2,2,2-Trifluoroacetic acid [ka] To a solution of 6-[[5-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (155 mg, 430 μmol) in dichloromethane (2 mL) was added TFA (490 mg, 331 μL, 4.3 mmol), and the reaction mixture was stirred at room temperature for 18 h. Volatiles were removed in vacuo to give 31.8 mg of the crude title compound as a viscous yellow oil (approximately 50% purity, major contaminant excess TFA), which was used without further purification. MS (ESI): m / z = 261.2 [M-TFA + H] +

[0266] Step a) 6-[[5-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester To a solution of 3,3,3-trifluoropropanehydrazide (CAS: 934171-99-0) (272 mg, 1.91 mmol) and tert-butyl 6-(2-amino-2-imino-ethyl)-2-azaspiro[3.3]heptane-2-carboxylate;acetic acid (B.349, step c)) (600 mg, 1.91 mmol) in DMF (5 mL) was added EtONa (195 mg, 2.87 mmol) at 25 °C under a N atmosphere. The reaction was then stirred at 100 °C under a N atmosphere for 12 h. The reaction was purified by preparative HPLC and lyophilized to afford the title compound (200 mg, 0.55 mmol, 29% yield) as a white solid. MS (ESI): m / z = 361.1 [M+H] + 1H NMR (400 MHz, methanol-d4) δ=3.92(s,2H),3.80(s,2H),3.67-3.50(m,2H),2.84(br d,J=7.2 Hz,2H),2.57(td,J=7.9,15.6 Hz,1H),2.31(ddd,J=2.4,8.0,10.4 Hz,2H),1.98-1.91(m,2H),1.42(s,9H)

[0267] Example B.526 5-(2,6-diazaspiro[3.3]heptan-2-ylmethyl)-3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazole;Trifluoroacetic acid [ka] To a solution of 6-[[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (231 mg, 595 μmol) in dichloromethane (1.98 mL) was added TFA (678 mg, 458 μL, 5.95 mmol), and the reaction mixture was stirred at room temperature for 18 hours. Volatiles were removed in vacuo to give 478 mg of the desired crude product as a pale yellow viscous oil, approximately 50% pure with excess TFA as the major contaminant. The crude product was used without further purification. MS (ESI): m / z = 289.2 [M+H] +

[0268] Step a) tert-butyl 6-[2-[(Z)-[amino-[1-(trifluoromethyl)cyclopropyl]methylene]amino]oxy-2-oxo-ethyl]-2,6-diazaspiro[3.3]heptane-2-carboxylate A solution of 2-(2-tert-butoxycarbonyl-2,6-diazaspiro[3.3]heptan-6-yl)acetic acid (CAS: 1937278-38-0) (1.45 g, 5.66 mmol) and CDI (1.1 g, 6.79 mmol) in DMF (10 mL) was stirred at room temperature for 3 hours. N'-hydroxy-1-(trifluoromethyl)cyclopropanecarboxamidine (CAS: 2172624-76-7) (951 mg, 5.66 mmol) was added to the solution and stirred at 30 °C for 12 hours. The reaction was purified by preparative HPLC (water (NH4HCO3)-ACN 27%-57%) to give the title compound (670 mg, 1.65 mmol, 29% yield) as a white solid. MS (ESI): m / z = 407.1 [M+H] + ; 1H NMR (400 MHz, chloroform-d) δ = 5.26 (br s, 1H), 4.09 (s, 1H), 4.02 (s, 3H), 3.97 (br s, 1H), 3.54 (s, 4H), 3.48-3.39 (m, 2H), 1.44 (s, 9H), 1.40-1.10 (m, 4H)

[0269] Step b) 6-[[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester A solution of tert-butyl 6-[2-[(Z)-[amino-[1-(trifluoromethyl)cyclopropyl]methylene]amino]oxy-2-oxo-ethyl]-2,6-diazaspiro[3.3]heptane-2-carboxylate (600 mg, 1.48 mmol) and Bu4NF (0.37 mL, 0.37 mmol, 0.25 equiv.) in THF (15 mL) was stirred at 70 °C for 1 h. The reaction was purified by preparative TLC (PE: EtOAc = 1:1) to give the crude product. The crude product was purified by preparative HPLC (water (FA)-ACN 18% to 48%) to give the title compound (260 mg, 0.67 mmol, 43% yield) as a yellow solid. MS (ESI): m / z = 389.0 [M+H] + ; 1 H NMR(400 MHz,chloroform-d)δ=4.00(s,4H),3.81(s,2H),3.52(s,4H),1.52(br d,J=3.3 Hz,2H),1.48(br d,J=3.0 Hz,2H),1.42(s,9H).

[0270] Example B.528 6-[(4-methylsulfonylpyrazol-1-yl)methyl]-2-azaspiro[3.3]heptane; 4-Methylbenzenesulfonic acid [ka] A mixture of tert-butyl 6-[(4-methylsulfonylpyrazol-1-yl)methyl]-2-azaspiro[3.3]heptane-2-carboxylate (1.29 g, 3.63 mmol) and p-toluenesulfonic acid (750 mg, 4.36 mmol) in EtOAc (50 mL) was stirred at 80 °C for 12 h under a N balloon. The reaction was concentrated, and the residue was dissolved in water (30 mL). The solution was lyophilized to afford the title compound (1.46 g, 3.41 mmol, 90% yield) as a pale yellow solid. MS (ESI): m / z = 256.2 [M+H] + ; 1 H NMR(400 MHz,chloroform-d)δ=8.58(br s,2H),7.93(s,1H),7.72(s,1H),7.62(d,J=8.0 Hz,2H),7.11(d,J=8.0 Hz,2H),4.10-3.85(m,6H),3.01(s,3H),2.54(dd,J=7.9,15.6 Hz,1H),2.28(s,3H),2.25-2.15(m,2H),1.95-1.86(m,2H).

[0271] Step a) tert-butyl 6-[(4-iodopyrazol-1-yl)methylene]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-2-azaspiro[3.3]heptane-2-carboxylate (45.6 g, 136 mmol), 4-iodopyrazole (24.0 g, 123 mmol), boric acid (7.65 g, 123 mmol), and pyridine (30 mL, 371 mmol) in DCE (230 mL) was added copper diacetate (49.4 g, 247 mmol) under an O atmosphere. The mixture was stirred at 70 °C under an O atmosphere for 12 hours. The reaction was concentrated. The residue was purified by flash chromatography on silica gel eluting with PE / EtOAc (4:1) to give the crude product, which was purified by preparative HPLC (water (FA)-ACN 55% to 75%) to give the title compound (17.7 g, 44.1 mmol, 35.6% yield) as a white solid. MS (ESI): m / z = 346.0 [M-C4H8+H]+

[0272] Step b) tert-butyl 6-[(4-methylsulfonylpyrazol-1-yl)methylene]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[(4-iodopyrazol-1-yl)methylene]-2-azaspiro[3.3]heptane-2-carboxylate (2.0 g, 4.98 mmol, 1.0 equiv.) in DMSO (30 mL) was added sodium methanesulfonate (1.18 g, 9.97 mmol, 2.0 equiv.), Cu(OTf) (361 mg, 1.0 mmol), and (R,R)-1,2-bis(N-methylamino)cyclohexane (142 mg, 1.0 mmol) at 110 °C for 12 h. The reaction was concentrated, and the residue was purified by silica gel flash chromatography eluting with PE / EtOAc (1:2) to afford the title compound (1.45 g, 4.1 mmol, 82% yield) as a white solid. MS (ESI): m / z = 298.1 [M-CH+H] +

[0273] Step c) tert-butyl 6-[(4-methylsulfonylpyrazol-1-yl)methyl]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[(4-methylsulfonylpyrazol-1-yl)methylene]-2-azaspiro[3.3]heptane-2-carboxylate (1.25 g, 3.54 mmol) in 50 mL of EtOAc was added Pd / C (0.5 g, 0.35 mmol) at 25 °C and stirred under a H balloon (760 mmHg) for 1 h. The reaction was filtered and concentrated to give the title compound (1.15 g, 3.24 mmol, 91% yield) as a white solid. MS (ESI): m / z = 300.3 [M-CH + H] +

[0274] Example B.529 6-[[4-(trifluoromethylsulfonyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane 4-methylbenzenesulfonic acid [ka] A mixture of tert-butyl 6-[[4-(trifluoromethylsulfonyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (630 mg, 1.54 mmol) and p-toluenesulfonic acid (317.97 mg, 1.85 mmol, 1.2 equiv) in EtOAc (20 mL) was stirred at 80 °C under a N balloon for 12 h. The reaction was concentrated, and the residue was dissolved in HO (30 mL). The solution was lyophilized to afford the title compound (738 mg, 1.53 mmol, 97% yield) as a pale yellow solid. MS (ESI): m / z = 310.1 [M+H] +

[0275] Step a) tert-butyl 6-[[4-(trifluoromethylsulfanyl)pyrazol-1-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[(4-iodopyrazol-1-yl)methylene]-2-azaspiro[3.3]heptane-2-carboxylate (B.528, step a) (30.0 mg, 0.07 mmol) in ACN (3 mL) was added silver(I) trifluoromethanethiolate (46.9 mg, 0.22 mmol), CuI (28.5 mg, 0.15 mmol), and 2-pyridin-2-ylpyridine (23.4 mg, 0.15 mmol) in a sealed tube at 90 °C for 12 h. The reaction was concentrated. The residue was purified by preparative HPLC (water (FA)-ACN] 52%-82%) to afford the title compound (13.0 mg, 0.03 mmol, 46% yield) as a yellow solid. MS (ESI): m / z = 320.1 [M-CH + H] +

[0276] Step b) tert-butyl 6-[[4-(trifluoromethylsulfanyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[[4-(trifluoromethylsulfanyl)pyrazol-1-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate (2.8 g, 7.46 mmol) in 50 mL of EtOAc was added Pd / C (1.0 g, 0.75 mmol) at 25 °C and stirred under a H balloon (760 mmHg) for 1 h. The reaction was filtered and concentrated to give the title compound (2.8 g, 7.42 mmol, 99% yield) as a white solid. MS (ESI): m / z = 322.2 [M-CH + H] +

[0277] Step c) tert-butyl 6-[[4-(trifluoromethylsulfonyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate To a solution of tert-butyl 6-[[4-(trifluoromethylsulfanyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (1.0 g, 2.65 mmol) in 1,2-dichloroethane (4 mL), ACN (4 mL), and water (8 mL) was added sodium periodate (1.13 g, 5.3 mmol) and ruthenium(III) chloride hydrate (59.7 mg, 0.26 mmol) at 0 °C, and the mixture was then stirred at 25 °C for 12 h. The reaction was concentrated. The residue was purified by preparative HPLC (water (FA)-ACN 50% to 80%) to afford the title compound (630 mg, 1.54 mmol, 58% yield) as a gray solid. MS (ESI): m / z = 354.3 [M-C4H8+H] +

[0278] Example B.530 [1-(2-Azaspiro[3.3]heptan-6-ylmethyl)pyrazol-4-yl]-imino-oxo-(trifluoromethyl)-λ6-sulfane; 4-Methylbenzenesulfonic acid [ka] A mixture of tert-butyl 6-[[4-(trifluoromethylsulfonimidoyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (650 mg, 1.59 mmol) and p-toluenesulfonic acid (329 mg, 1.91 mmol) in EtOAc (10 mL) was stirred at 80 °C under a N balloon for 12 h. The reaction was concentrated, and the residue was dissolved in HO (30 mL). The solution was lyophilized to afford the title compound (623 mg, 1.3 mmol, 77% yield) as a pale yellow oil. MS (ESI): m / z = 309.1 [M+H] +

[0279] Step a) tert-butyl 6-[[4-(trifluoromethylsulfonimidoyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate A mixture of tert-butyl 6-[[4-(trifluoromethylsulfanyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (B.529, step b) (1.8 g, 4.77 mmol), PhI(OAc) (6.14 g, 19.1 mmol), and NHCOONH (1.49 g, 19.1 mmol) in TFE was stirred at 30 °C for 12 h. The reaction was concentrated. The residue was purified by preparative HPLC (water (FA)-ACN, 60%-80%) to give the title compound (650 mg, 1.59 mmol, 33% yield) as a gray solid. MS (ESI): m / z = 353.1 [M-CH + H] +

[0280] Example C.10 3-Bromo-5-[1-(trifluoromethyl)cyclopropyl]-1H-1,2,4-triazole To a solution of 3-[1-(trifluoromethyl)cyclopropyl]-1H-1,2,4-triazole (5.07 g, 27.2 mmol) in N,N-dimethylformamide (25 mL) was added NBS (10.7 g, 59.8 mmol). The mixture was stirred at 60 °C for 15 h. The reaction mixture was poured into EtOAc and washed with water and brine. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (0% to 20% AcOEt in heptane) to give the title compound (3.08 g, 42.0%) as a white solid. MS (ESI): m / z = 255.9 / 257.9 [M+H] +

[0281] Step a) (NE)-N-(dimethylaminomethylene)-1-(trifluoromethyl)cyclopropanecarboxamide 1-(Trifluoromethyl)cyclopropanecarboxamide (5.0 g, 32.7 mmol) was dissolved in N,N-dimethylformamide dimethyl acetal (27.2 g, 30.4 mL, 229 mmol). The mixture was stirred at room temperature for 6 hours. The reaction mixture was poured into EtOAc and washed with water (3 times) and brine. The organic layer was dried over Na2SO4 and concentrated under reduced pressure to give the title compound (6.5 g, 90.8%) as a yellow amorphous solid. MS (ESI): m / z = 209.1 [M+H] +

[0282] Step b) 3-[1-(trifluoromethyl)cyclopropyl]-1H-1,2,4-triazole To a glacially cooled solution of (NE)-N-(dimethylaminomethylene)-1-(trifluoromethyl)cyclopropanecarboxamide (6.5 g, 28.1 mmol) in acetic acid (18 mL) was added hydrazine hydrate (1.55 g, 1.5 mL, 30.9 mmol). The mixture was stirred at room temperature for 2 hours and then at 50°C for 2 hours. The reaction mixture was concentrated in vacuo and dissolved in EtOAc. 1N aqueous NaOH was added (pH 7-8). The mixture was washed with water and brine. The organic layer was dried over NaSO and concentrated under reduced pressure to give the title compound (5.07 g, 96.8%) as a yellow solid. MS (ESI): m / z = 178.1 [M+H] +

[0283] Example C.11 4,5-Dibromo-2-(2,2,2-trifluoroethyl)triazole To a solution of 4,5-dibromo-2H-triazole (5.0 g, 22.0 mmol) in ACN (50 mL) was added cesium carbonate (7.18 g, 22.0 mmol). 2,2,2-Trifluoroethyl trifluoromethanesulfonate (5.12 g, 22.0 mmol) was then added dropwise at 0 °C. The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was poured into water, EtOAc was added, and the aqueous layer was extracted three times with EtOAc. The combined organic layers were then washed with water and brine, dried over Na2SO4, filtered, and evaporated. The crude product was purified by column chromatography (silica gel, PE / EtOAc 0–7%). The fractions containing the pure product were combined and evaporated to give 4,5-dibromo-2-(2,2,2-trifluoroethyl)triazole (5.3 g, 17.2 mmol, 77.9% yield) as a yellow oil. 1 H NMR (400 MHz, chloroform-d) δ = 4.95 (q, J = 7.9 Hz, 2H)

[0284] Example C.12 3-Bromo-1-(2,2,2-trifluoroethyl)-1,2,4-triazole To a solution of 3-bromo-1H-1,2,4-triazole (8000 mg, 54.1 mmol) in THF (80 mL) was added NaH (3.89 g, 97.3 mmol) at 0 °C. After 0.5 h, 2,2,2-trifluoroethyl trifluoromethanesulfonate (25.1 g, 108 mmol) was added, and the resulting mixture was stirred at 20 °C for 12 h. The reaction mixture was poured into water (200 mL) and extracted with EtOAc (200 mL x 3). The combined extracts were washed with brine (150 mL), dried over NaSO, filtered, and concentrated under reduced pressure to give a residue. The residue was purified by preparative HPLC and concentrated under reduced pressure to give the title compound (6000 mg, 26.1 mmol, 48.3% yield) as a brown oil. MS (ESI): m / z = 229.9 [M+H] + ; 1 H NMR (400 MHz, chloroform-d) δ = 12.49 (s, 1H), 9.14 (q, J = 8.1 Hz, 2H)

[0285] Example C.13 4-Dimethylphosphoryl-2-methyl-pyrazole-3-carbaldehyde To a solution of 4-iodo-2-methyl-pyrazole-3-carbaldehyde (CAS: 959986-66-4) (2000 mg, 8.47 mmol) in 1,4-dioxane (20 mL) was added TEA (2.36 mL, 17.0 mmol), dimethylphosphine oxide (794 mg, 10.2 mmol, 1.2 equiv.), Xantphos (981 mg, 1.69 mmol), and Pd(dba) (776 mg, 0.85 mmol). The reaction mixture was stirred at 70 °C under a N atmosphere for 12 h. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by reverse flash chromatography (FA conditions; MeCN:HO = 0-30%) and lyophilized to give the title compound as a pale yellow solid. MS (ESI): m / z = 187.0 [M+H] + ; 1 H NMR (400 MHz, chloroform-d) δ ppm 1.81 (s, 3 H), 1.84 (s, 3 H), 4.25 (s, 3 H), 7.60 (br d, J = 1.83 Hz, 1 H), 10.49 (s, 1 H).

[0286] Example C.17 3-Bromo-5-[1-(trifluoromethyl)cyclopropyl]-1H-pyrazole To a solution of 5-[1-(trifluoromethyl)cyclopropyl]-1H-pyrazol-3-amine (2.3 g, 12.0 mmol) in ACN (40 mL) was added dropwise a solution of isopentyl nitrite (1.55 g, 13.2 mmol) in ACN (5 mL) at 0 °C. The reaction was stirred at 0 °C for 1 h. CuBr (1.61 g, 7.22 mmol) was then added to the mixture at 0 °C, and the resulting mixture was stirred at 20 °C for 12 h. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by reverse-phase HPLC (water (0.1% FA)-ACN). The purified solution was lyophilized to give the title compound (740 mg, 2.9 mmol, 24.1% yield) as a pale green solid. MS (ESI): m / z = 257.2 [M+H] + .

[0287] Example C.22 1-(3,3,3-trifluoropropyl)pyrazole-3-carbaldehyde To a solution of 1H-pyrazole-3-carbaldehyde (5.0 g, 52.0 mmol) in N,N-dimethylformamide (100 mL) were added 1,1,1-trifluoro-3-iodopropane (17.5 g, 78.1 mmol), CsCO (33.9 g, 104 mmol, 2.0 equiv.), and 18-crown-6 (6.88 g, 26.02 mmol, 0.5 equiv.). The reaction mixture was stirred at 90 °C for 3 h. Then, 1,1,1-trifluoro-3-iodopropane (17.5 g, 78.1 mmol) and 18-crown-6 (6.88 g, 26.0 mmol) were added to the mixture, and the resulting mixture was stirred at 90 °C for an additional 60 h. The reaction mixture was poured into water (200 mL) and then extracted with ethyl acetate (100 mL × 3). The combined organic layers were washed with brine (100 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to give a residue. The residue was purified by flash chromatography on silica gel eluting with PE / EtOAc (3:1) to give the product 1-(3,3,3-trifluoropropyl)pyrazole-3-carbaldehyde (1.15 g, 5.99 mmol, 12% yield) as a yellow oil. MS (ESI): m / z = 193.1 [M+H]; 1 H NMR(400 MHz,chloroform-d)δ=9.96(s,1H),7.48(d,J=2.1 Hz,1H),6.81(d,J=2.4 Hz,1H),4.46(t,J=7.2 Hz,2H),2.82(tq,J=7.2,10.2 Hz,2H).

[0288] Example C.23 2-[[2-Bromo-4-(trifluoromethyl)imidazol-1-yl]methoxy]ethyl-trimethyl-silane A mixture of trimethyl-[2-[[4-(trifluoromethyl)imidazol-1-yl]methoxy]ethyl]silane (30.0 g, 113 mmol), N-bromosuccinimide (26.1 g, 146 mmol), and AIBN (3.7 g, 22.5 mmol) in carbon tetrachloride (300 mL) was stirred at 60 °C for 12 h. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by back-flush (FA conditions; MeCN:HO 0-70%) and lyophilized to give the title compound (21.0 g, 60.8 mmol, 54% yield) as a yellow oil. MS (ESI): m / z = 346.9 [M+H] + ; 1 H NMR (400 MHz, chloroform-d) δ = 7.45 (s, 1H), 5.30 (s, 2H), 3.66-3.53 (m, 2H), 1.02-0.89 (m, 2H), 0.01 (s, 9H)

[0289] Example 361 The compounds of formula (I) can be used in a manner known per se as active ingredient to prepare tablets of the following composition:

[0290] Per tablet Active ingredient 200mg Microcrystalline cellulose 155mg Cornstarch 25mg Talc 25mg Hydroxypropyl methylcellulose 20mg 425mg

[0291] Example 362 The compounds of formula (I) can be used in a manner known per se as active ingredients to prepare capsules of the following composition:

[0292] Per capsule Active ingredient 100.0mg Cornstarch 20.0mg Lactose 95.0mg Talc 4.5mg Magnesium stearate 0.5mg 220.0mg

Claims

1. Compounds of formula (I) 【Transformation 87】 or a pharmaceutically acceptable salt thereof, W and Z each independently represent CH ２ and C.H. ２ CH ２ Selected from: Y is selected from CH and N; U is selected from CH and N; V is selected from NH, O and S; X is selected from NH and O; L is CH ２ and O; A is selected from: 【Chemical 88】 B is selected from: 【Chemistry 89】 and 9-membered fused bicyclic heteroaryl containing 1 to 3 heteroatoms selected from N, O and S, with the remaining ring atoms being carbon; R １ is hydrogen, halogen, cyano, 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, halo-C ３ -C １０ -cycloalkyl, C ３ -C １０ -cycloalkyl-C １ -C ６ -Alkyl, halo-C １ -C ６ -Alkyl-C ３ -C １０ -cycloalkyl, C ６ -C １４ -aryl, sulfamoyl, group [Chemical 90] and (C １ -C ６ -alkyl) ２ PO-; R １ａ is C １ -C ６ -Alkyl and halo-C １ -C ６ - selected from alkyl; R ２ is hydrogen, halogen, cyano, C １ -C ６ -Alkyl, C １ -C ６ -alkoxy, halo-C １ -C ６ -alkyl, and halo-C １ -C ６ -alkoxy; and R ３ is C ３ -C １０ -cycloalkyl, hydroxy-C ３ -C １０ -cycloalkyl, amino-C ３ -C １０ -cycloalkyl, halo-C ３ -C １０ -cycloalkyl, C １ -C ６ -Alkyl, halo-C １ -C ６ -Alkyl, C １ -C ６ -alkoxy and halo-C １ -C ６ - selected from alkoxy, The compound, or a pharmaceutically acceptable salt thereof.

2. A is 【Chemistry 91】 2. The compound of formula (I) according to claim 1, selected from: or a pharmaceutically acceptable salt thereof.

3. A is 【Chemistry 92】 3. The compound of formula (I) according to claim 2, wherein:

4. A compound of formula (I) according to any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, W and Z are both CH ２ or W and Z are both CH ２ CH ２ and Y is selected from CH and N; The compound, or a pharmaceutically acceptable salt thereof.

5. 3. A compound of formula (I) according to claim 2, or a pharmaceutically acceptable salt thereof, W and Z are both CH ２ and Y is CH; The compound, or a pharmaceutically acceptable salt thereof.

6. 6. A compound of formula (I) according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein B is 【Chemistry 93】 or a pharmaceutically acceptable salt thereof.

7. 7. A compound of formula (I) according to claim 6, or a pharmaceutically acceptable salt thereof, wherein B is 【Chemical 94】 or a pharmaceutically acceptable salt thereof.

8. 8. A compound of formula (I) according to claim 7, or a pharmaceutically acceptable salt thereof, wherein B is 【Chemical 95】 or a pharmaceutically acceptable salt thereof.

9. L is CH ２ 9. The compound of formula (I) according to any one of claims 1 to 8, wherein:

10. A compound of formula (I) according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, R １ But hydrogen, cyano, C １ -C ６ -Alkyl, halo-C １ -C ６ -Alkyl, C ３ -C １０ -cycloalkyl, C ３ -C １０ -cycloalkyl-C １ -C ６ -Alkyl, halo-C １ -C ６ -Alkyl-C ３ -C １０ -cycloalkyl, C ６ -C １４ -aryl, sulfamoyl, group 【Chemistry 96】 and (C １ -C ６ -alkyl) ２ PO-; R １ａ But C １ -C ６ -Alkyl and halo-C １ -C ６ - alkyl; and X is selected from NH and O; The compound, or a pharmaceutically acceptable salt thereof.

11. 11. A compound of formula (I) according to claim 10, or a pharmaceutically acceptable salt thereof, R １ is hydrogen, methyl, ethyl, tert-butyl, cyano, CHF ２ , C.F. ３ , 1,1-difluoroethyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, sulfamoyl, dimethylphosphoryl, phenyl, and (CF ３ ) cyclopropyl; R １ａ However, methyl and CF ３ is selected from: X is selected from NH and O; The compound, or a pharmaceutically acceptable salt thereof.

12. 11. A compound of formula (I) according to claim 10, or a pharmaceutically acceptable salt thereof, R １ But, Halo-C １ -C ６ -Alkyl, C ３ -C １０ -cycloalkyl, halo-C １ -C ６ -Alkyl-C ３ -C １０ -cycloalkyl, and groups 【Chemistry 97】 Selected from: R １ａ But, Halo-C １ -C ６ - alkyl; and X is selected from NH and O; The compound, or a pharmaceutically acceptable salt thereof.

13. 13. A compound of formula (I) according to claim 12, or a pharmaceutically acceptable salt thereof, R １ But CHF ２ , C.F. ３ , 2,2,2-trifluoroethyl, cyclopropyl, (CF ３ ) cyclopropyl, and groups 【Chem.98】 Selected from: R １ａ But CF ３ and X is selected from NH and O; The compound, or a pharmaceutically acceptable salt thereof.

14. 14. A compound of formula (I) according to claim 13, or a pharmaceutically acceptable salt thereof, R １ But CF ３ , cyclopropyl, (CF ３ ) cyclopropyl, and groups 【Chem.99】 Selected from: R １ａ But CF ３ and X is selected from NH and O; The compound, or a pharmaceutically acceptable salt thereof.

15. R ２ But hydrogen, C １ -C ６ -Alkyl and halo-C １ -C ６ 15. The compound of formula (I) according to any one of claims 1 to 14, or a pharmaceutically acceptable salt thereof, wherein: - alkyl is selected from:

16. R ２ is hydrogen, methyl, ethyl and CF ３ 16. A compound of formula (I) according to claim 15, selected from: or a pharmaceutically acceptable salt thereof.

17. R ２ is hydrogen, methyl, and CF ３ 17. A compound of formula (I) according to claim 16, selected from: or a pharmaceutically acceptable salt thereof.

18. R ２ 18. The compound of formula (I) according to claim 17, or a pharmaceutically acceptable salt thereof, wherein is hydrogen.

19. R ３ But C ３ -C １０ -cycloalkyl, hydroxy-C ３ -C １０ -cycloalkyl, amino-C ３ -C １０ -cycloalkyl, and halo-C １ -C ６ 19. A compound of formula (I) according to any one of claims 1 to 18, or a pharmaceutically acceptable salt thereof, selected from: - alkyl.

20. R ３ is cyclopropyl, 1-hydroxycyclopropyl, 1-aminocyclopropyl, and CF ３ 20. The compound of formula (I) according to claim 19, selected from: or a pharmaceutically acceptable salt thereof.

21. R ３ But C ３ -C １０ -cycloalkyl and halo-C １ -C ６ 20. The compound of formula (I) according to claim 19, or a pharmaceutically acceptable salt thereof, wherein: - alkyl is selected from:

22. R ３ but cyclopropyl and CF ３ 22. The compound of formula (I) according to claim 21, selected from: or a pharmaceutically acceptable salt thereof.

23. 10. A compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, W and Z are each independently CH ２ and C.H. ２ CH ２ Selected from: Y is selected from CH and N; U is selected from CH and N; V is selected from NH, O and S; X is selected from NH and O; L is CH ２ and O; A is, 【Chemistry 100】 Selected from: B is selected from: 【Chemistry 101】 R １ But hydrogen, cyano, C １ -C ６ -Alkyl, halo-C １ -C ６ -Alkyl, C ３ -C １０ -cycloalkyl, C ３ -C １０ -cycloalkyl-C １ -C ６ -Alkyl, halo-C １ -C ６ -Alkyl-C ３ -C １０ -cycloalkyl, C ６ -C １４ -aryl, sulfamoyl, group 【Chemical Engineering 102】 and (C １ -C ６ -alkyl) ２ PO-; R １ａ But C １ -C ６ -Alkyl and halo-C １ -C ６ - selected from alkyl; R ２ But hydrogen, C １ -C ６ -alkyl, and halo-C １ -C ６ - alkyl; and R ３ But C ３ -C １０ -cycloalkyl, hydroxy-C ３ -C １０ -cycloalkyl, amino-C ３ -C １０ -cycloalkyl, halo-C １ -C ６ - selected from alkyl, The compound, or a pharmaceutically acceptable salt thereof.

24. 24. A compound of formula (I) according to claim 23, or a pharmaceutically acceptable salt thereof, W and Z are both CH ２ Is it; or W and Z are both CH ２ CH ２ and Y is selected from CH and N; X is selected from NH and O; L is CH ２ and A is, 【Chemistry 103】 Selected from: B is selected from: 【Chemical 104】 R １ But, Halo-C １ -C ６ -Alkyl, C ３ -C １０ -cycloalkyl, halo-C １ -C ６ -Alkyl-C ３ -C １０ -cycloalkyl, and groups 【Chemistry 105】 Selected from: R １ａ But, Halo-C １ -C ６ - alkyl; R ２ But hydrogen, C １ -C ６ -alkyl, and halo-C １ -C ６ - alkyl; and R ３ But C ３ -C １０ -cycloalkyl, hydroxy-C ３ -C １０ -cycloalkyl, halo-C １ -C ６ - selected from alkyl, The compound, or a pharmaceutically acceptable salt thereof.

25. 25. A compound of formula (I) according to claim 24, or a pharmaceutically acceptable salt thereof, W and Z are both CH ２ Is it; or W and Z are both CH ２ CH ２ and Y is selected from CH and N; X is selected from NH and O; L is CH ２ and A is, 【Chemistry 106】 Selected from: B is selected from: 【Chemistry 107】 R １ But CHF ２ , C.F. ３ , 2,2,2-trifluoroethyl, cyclopropyl, (CF ３ ) cyclopropyl, and groups 【Chemistry 108】 Selected from: R １ａ But CF ３ and R ２ is hydrogen, methyl and CF ３ is selected from: R ３ cyclopropyl, hydroxycyclopropyl and CF ３ Selected from: The compound, or a pharmaceutically acceptable salt thereof.

26. 2. A compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-5-(trifluoromethyl)pyrazol-4-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-[[1-methyl-5-(trifluoromethyl)pyrazol-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-methyl-4-(trifluoromethyl)pyrazol-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-[[5-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1H-pyrazol-5-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)pyrazol-1-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-[[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]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-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1H-1,2,4-triazol-3-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-(trifluoromethyl)-1H-1,2,4-triazol-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-[[5-(trifluoromethyl)-1H-1,2,4-triazol-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-[[4-(trifluoromethyl)pyrazol-1-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-[4-(trifluoromethyl)thiazol-2-yl]oxy-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-[[1-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(trifluoromethyl)-1,2,4-thiadiazol-5-yl]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-(trifluoromethyl)-1,2,4-thiadiazol-5-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-[[3-(trifluoromethyl)-1,2,4-thiadiazol-5-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]-[7-[[3-(trifluoromethyl)isoxazol-5-yl]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-[[2-(trifluoromethyl)thiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(trifluoromethyl)-1,2,4-thiadiazol-3-yl]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-(trifluoromethyl)-1,2,4-thiadiazol-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-[[5-(trifluoromethyl)-1,2,4-thiadiazol-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-[[4-(trifluoromethyl)oxazol-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [7-[[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-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]-[7-[[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]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-[[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [7-[[5-(trifluoromethyl)-1H-pyrazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-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]-[7-[[5-(trifluoromethyl)-1H-pyrazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(difluoromethyl)thiazol-2-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [7-[[5-(difluoromethyl)thiazol-2-yl]methyl]-2,7-diazaspiro[3.5]nonan-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]-[7-[[5-(difluoromethyl)thiazol-2-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [7-[[5-(difluoromethyl)thiazol-2-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.5]nonan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.5]nonan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.5]nonan-2-yl]methanone; 1-[[2-[6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptane-2-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]pyrazole-4-carbonitrile; 1-[[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]pyrazole-4-carbonitrile; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)imidazol-1-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-(trifluoromethyl)imidazol-1-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-[[4-(trifluoromethyl)imidazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(3-cyclopropyl-1,2,4-thiadiazol-5-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[(3-cyclopropyl-1,2,4-thiadiazol-5-yl)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-[(3-cyclopropyl-1,2,4-thiadiazol-5-yl)methyl]-2,6-diazaspiro[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-1,2,4-thiadiazol-5-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [7-[[5-(trifluoromethyl)isothiazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-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]-[7-[[5-(trifluoromethyl)isothiazol-3-yl]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-[[5-(trifluoromethyl)isothiazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [6-[[5-(trifluoromethyl)-1H-pyrazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1H-pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[4-(trifluoromethyl)thiazol-2-yl]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-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)thiazol-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]-[6-[[4-(trifluoromethyl)thiazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[5-methyl-4-(trifluoromethyl)thiazol-2-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-methyl-4-(trifluoromethyl)thiazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[(2-tert-butylthiazol-5-yl)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-tert-butylthiazol-5-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(2-tert-butylthiazol-5-yl)methyl]-2,6-diazaspiro[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-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]oxy-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-[1-(trifluoromethyl)cyclopropyl]pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[1-cyclopropyl-3-(trifluoromethyl)pyrazol-4-yl]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-[[1-cyclopropyl-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[1-cyclopropyl-3-(trifluoromethyl)pyrazol-4-yl]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-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[2-methyl-4-(trifluoromethyl)pyrazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [7-[[2-methyl-4-(trifluoromethyl)pyrazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-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]-[7-[[2-methyl-4-(trifluoromethyl)pyrazol-3-yl]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-[[2-methyl-4-(trifluoromethyl)pyrazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [6-[[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]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-methyl-3-(trifluoromethyl)pyrazol-1-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-[[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-methyl-5-(trifluoromethyl)pyrazol-1-yl]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-methyl-5-(trifluoromethyl)pyrazol-1-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-[[3-methyl-5-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-triazol-1-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-[[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-triazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(4-cyclobutylthiadiazol-5-yl)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-cyclobutylthiadiazol-5-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(4-cyclobutylthiadiazol-5-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [7-[[5-(trifluoromethyl)isoxazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-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]-[7-[[5-(trifluoromethyl)isoxazol-3-yl]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-[[5-(trifluoromethyl)isoxazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [6-[[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]methyl]-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]-[6-[[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[2-methyl-4-(trifluoromethyl)thiazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-methyl-4-(trifluoromethyl)thiazol-5-yl]methyl]-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]-[6-[[2-methyl-4-(trifluoromethyl)thiazol-5-yl]methyl]-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]-[6-(1-methylpyrazol-4-yl)oxy-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(4-cyclopropylthiadiazol-5-yl)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-cyclopropylthiadiazol-5-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(difluoromethyl)-3-methyl-pyrazol-1-yl]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-(difluoromethyl)-3-methyl-pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(difluoromethyl)-3-methyl-pyrazol-1-yl]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-(difluoromethyl)-5-methyl-pyrazol-1-yl]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-(difluoromethyl)-5-methyl-pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(difluoromethyl)-5-methyl-pyrazol-1-yl]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-[(4-tert-butyloxazol-2-yl)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-tert-butyloxazol-2-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(2,2,2-trifluoroethyl)pyrazol-3-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(2,2,2-trifluoroethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[5-[1-(trifluoromethyl)cyclopropyl]-1H-1,2,4-triazol-3-yl]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-[1-(trifluoromethyl)cyclopropyl]-1H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)triazol-1-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-(trifluoromethyl)triazol-1-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-[[5-(trifluoromethyl)-1,2,4-oxadiazol-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-[[4-(trifluoromethyl)thiazol-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(2,2,2-trifluoroethyl)triazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(2,2,2-trifluoroethyl)triazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]methyl]-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]-[6-[[3-methyl-1-(2,2,2-trifluoroethyl)pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[3-methyl-1-(2,2,2-trifluoroethyl)pyrazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-methyl-1-(2,2,2-trifluoroethyl)pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[5-methyl-1-(2,2,2-trifluoroethyl)pyrazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-methyl-1-(2,2,2-trifluoroethyl)pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(trifluoromethyl)pyrazol-3-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(trifluoromethyl)pyrazol-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)-1H-pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(trifluoromethyl)-1H-pyrazol-4-yl]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-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]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-[[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(3-cyclopropyl-1H-pyrazol-5-yl)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-1H-pyrazol-5-yl)methyl]-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-pyrazol-5-yl)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-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)-1,2,4-triazol-1-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-[[3-(trifluoromethyl)-1,2,4-triazol-1-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-[[3-(trifluoromethyl)-1,2,4-triazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[4-(trifluoromethyl)-1H-pyrazol-3-yl]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-(trifluoromethyl)-1H-pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-cyclopropyl-3-methyl-pyrazol-1-yl)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-cyclopropyl-3-methyl-pyrazol-1-yl)methyl]-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-[(5-cyclopropyl-3-methyl-pyrazol-1-yl)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-cyclopropyl-5-methyl-pyrazol-1-yl)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-5-methyl-pyrazol-1-yl)methyl]-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-5-methyl-pyrazol-1-yl)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-[[2-methyl-5-(trifluoromethyl)triazol-4-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-[[3-(trifluoromethyl)-1,2,4-oxadiazol-5-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-(2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[2-(2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol-3-yl]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-[[2-(2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(3-cyclopropyl-pyrazol-1-yl)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-cyclopropylpyrazol-1-yl)methyl]-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-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(2,2,2-trifluoroethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(trifluoromethyl)imidazol-1-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)imidazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)thiazol-2-yl]methyl]-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]-[6-[[5-(trifluoromethyl)thiazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(trifluoromethyl)thiazol-2-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)thiazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)isothiazol-5-yl]methyl]-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]-[6-[[3-(trifluoromethyl)isothiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(trifluoromethyl)isothiazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)isothiazol-5-yl]methyl]-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]-[6-[[5-(trifluoromethyl)isothiazol-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)isothiazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-methyl-4-(trifluoromethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[2-methyl-4-(trifluoromethyl)pyrazol-3-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-methyl-4-(trifluoromethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-5-(trifluoromethyl)pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-methyl-5-(trifluoromethyl)pyrazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-5-(trifluoromethyl)pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[2-ethyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[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-ethyl-5-(trifluoromethyl)pyrazol-3-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-ethyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[4-(trifluoromethyl)thiazol-2-yl]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-[[4-(trifluoromethyl)thiazol-2-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [7-[[4-(trifluoromethyl)thiazol-2-yl]methyl]-2,7-diazaspiro[3.5]nonan-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]-[7-[[4-(trifluoromethyl)thiazol-2-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [6-[[4-(trifluoromethyl)isothiazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)isothiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(trifluoromethyl)pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(trifluoromethyl)pyrazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(trifluoromethyl)pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(trifluoromethyl)isoxazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)isoxazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(difluoromethyl)thiazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(difluoromethyl)thiazol-2-yl]methyl]-2,6-diazaspiro[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-(difluoromethyl)thiazol-2-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(difluoromethyl)thiazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(trifluoromethyl)isoxazol-3-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)isoxazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[2-(2,2,2-trifluoroethyl)tetrazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(2,2,2-trifluoroethyl)tetrazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[2-(2,2,2-trifluoroethyl)triazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(2,2,2-trifluoroethyl)triazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(2,2,2-trifluoroethyl)tetrazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(2,2,2-trifluoroethyl)tetrazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[(4-tert-butylthiazol-2-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(4-tert-butylthiazol-2-yl)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-tert-butylthiazol-2-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-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-[[2-(2,2,2-trifluoroethyl)triazol-4-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-[[1-(2,2,2-trifluoroethyl)-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl]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-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[(5-tert-butyl-1,3,4-thiadiazol-2-yl)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-[(5-tert-butyl-1,3,4-thiadiazol-2-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-tert-butyl-1,3,4-thiadiazol-2-yl)methyl]-2,6-diazaspiro[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-(trifluoromethyl)oxazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(trifluoromethyl)oxazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[2-(trifluoromethyl)oxazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(trifluoromethyl)oxazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)oxazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[4-(trifluoromethyl)oxazol-2-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)oxazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(trifluoromethyl)isoxazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)isoxazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(trifluoromethyl)oxazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)oxazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[2-(2,2,2-trifluoroethyl)pyrazol-3-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(2,2,2-trifluoroethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(trifluoromethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[2-(trifluoromethyl)pyrazol-3-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(trifluoromethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[(4-dimethylphosphoryl-2-methyl-pyrazol-3-yl)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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-dimethylphosphoryl-2-methyl-pyrazol-3-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)-1H-1,2,4-triazol-5-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-[[3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(trifluoromethyl)-1H-imidazol-2-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1H-imidazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(2,2,2-trifluoroethyl)imidazol-2-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(2,2,2-trifluoroethyl)imidazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(trifluoromethyl)imidazol-2-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(trifluoromethyl)imidazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(trifluoromethyl)-1H-imidazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1H-imidazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[(4-cyclopropylthiazol-2-yl)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-cyclopropylthiazol-2-yl)methyl]-2,6-diazaspiro[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-(trifluoromethyl)-1H-pyrazol-3-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1H-pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-methyl-5-(trifluoromethyl)triazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-5-(trifluoromethyl)triazol-4-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-[(3-phenyl-1,2,4-oxadiazol-5-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[1-methyl-5-(trifluoromethyl)pyrazol-4-yl]oxy-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-[1-methyl-5-(trifluoromethyl)pyrazol-4-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[1-(2,2,2-trifluoroethyl)pyrazol-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-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; 2-methyl-4-[[2-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methyl]pyrazole-3-sulfonamide; 4-[[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]-2-methyl-pyrazole-3-sulfonamide; [6-[(4-tert-butyl-1H-imidazol-2-yl)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-tert-butyl-1H-imidazol-2-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-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-[[1-(2,2,2-trifluoroethyl)triazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(4-tert-butylisoxazol-3-yl)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-tert-butylisoxazol-3-yl)methyl]-2,6-diazaspiro[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-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(1H-pyrazol-3-ylmethyl)-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(1,1-difluoroethyl)-1,2,4-oxadiazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(1,1-difluoroethyl)-1,2,4-oxadiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[2-(2,2-difluoroethyl)pyrazol-3-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(2,2-difluoroethyl)pyrazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(difluoromethyl)pyrazol-4-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(difluoromethyl)pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(cyclopropylmethyl)-1,2,4-oxadiazol-5-yl]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-[[3-(cyclopropylmethyl)-1,2,4-oxadiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(3-tert-butyl-1,2,4-oxadiazol-5-yl)methyl]-2,6-diazaspiro[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-5-methyl-isoxazol-4-yl)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-[(3-cyclopropyl-5-methyl-isoxazol-4-yl)methyl]-2,6-diazaspiro[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-5-methyl-isoxazol-4-yl)methyl]-2,6-diazaspiro[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-cyclopropyl-2-methyl-pyrazol-3-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-cyclopropyl-2-methyl-pyrazol-3-yl)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-[(5-cyclopropyl-2-methyl-pyrazol-3-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-cyclobutyl-1H-pyrazol-3-yl)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-[(5-cyclobutyl-1H-pyrazol-3-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(2-tert-butylpyrazol-3-yl)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-tert-butylpyrazol-3-yl)methyl]-2,6-diazaspiro[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-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(2-methylpyrazol-3-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[2-(difluoromethyl)thiazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(difluoromethyl)thiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; 1-methyl-5-[[2-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methyl]imidazole-4-carbonitrile; 5-[[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]-1-methyl-imidazole-4-carbonitrile; 5-[[2-[6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methyl]-1-methyl-imidazole-4-carbonitrile; [6-[(3-cyclopropyl-1H-pyrazol-5-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(1H-pyrazol-3-ylmethyl)-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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-(pyrazolo[1,5-a]pyridin-3-ylmethyl)-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[(3-ethyl-1,2,4-thiadiazol-5-yl)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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(3-ethyl-1,2,4-thiadiazol-5-yl)methyl]-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]-[6-[[2-methyl-5-(trifluoromethyl)pyrazol-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-[[1-methyl-4-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(2,2,2-trifluoroethyl)pyrazol-4-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-[[1-(2,2,2-trifluoroethyl)pyrazol-4-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-[[4-(trifluoromethyl)triazol-2-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-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(difluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(difluoromethyl)-1H-pyrazol-5-yl]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-(difluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]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-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)-1H-pyrazol-5-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-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(3-cyclopropyl-1H-1,2,4-triazol-5-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-[(2,4-dimethylthiazol-5-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[(5-cyclopropyl-1H-1,2,4-triazol-3-yl)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-cyclopropyl-1H-1,2,4-triazol-3-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-[(1-methylimidazol-4-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-[(2-ethyl-4-methyl-1H-imidazol-5-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-[(2,4-dimethyloxazol-5-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-[(1-methylimidazol-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]-[6-[(1,5-dimethylpyrazol-4-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1H-pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(3,3,3-trifluoropropyl)pyrazol-3-yl]methyl]-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]-[6-[(4-mesylpyrazol-1-yl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[4-methyl-5-(trifluoromethyl)-1,2,4-triazol-3-yl]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-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.5]nonan-2-yl]methanone; [6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [7-[[3-(trifluoromethyl)isoxazol-5-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-cyclopropyl-1H-1,2,4-triazol-3-yl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(1-tert-butylimidazol-2-yl)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-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1H-1,2,4-triazol-3-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-[[1-(3,3,3-trifluoropropyl)pyrazol-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-[[4-methyl-5-(trifluoromethyl)-1,2,4-triazol-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)-1,2,4-oxadiazol-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethylsulfonimidoyl)pyrazol-1-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-[[5-(trifluoromethyl)-1,2,4-triazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)-1H-imidazol-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(4-mesylpyrazol-1-yl)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-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-5-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[3-(trifluoromethyl)isoxazol-5-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [6-[3-(1-aminocyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(2,2,2-trifluoroethyl)-1,2,4-triazol-3-yl]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-mesylpyrazol-1-yl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1,2,4-triazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(difluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-[1-(trifluoromethyl)cyclopropyl]-1H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(2,2,2-trifluoroethyl)triazol-4-yl]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-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)-1H-imidazol-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-[[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-5-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-[[1-(2,2,2-trifluoroethyl)-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[2-(2,2,2-trifluoroethyl)triazol-4-yl]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-[[4-(trifluoromethylsulfonimidoyl)pyrazol-1-yl]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-cyclopropyl-1H-pyrazol-3-yl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)-1H-pyrazol-3-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-(trifluoromethyl)-1,2,4-triazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1H-pyrazol-4-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-[[1-(2,2,2-trifluoroethyl)triazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[4-(trifluoromethyl)-1H-imidazol-2-yl]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-(trifluoromethylsulfonimidoyl)pyrazol-1-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-[[2-(2,2,2-trifluoroethyl)triazol-4-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-(trifluoromethyl)-1H-imidazol-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-[1-(trifluoromethyl)cyclopropyl]-1H-pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-triflylpyrazol-1-yl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[5-[1-(trifluoromethyl)cyclopropyl]-1H-pyrazol-3-yl]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-cyclopropylpyrazol-1-yl)methyl]-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-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-triflylpyrazol-1-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-[1-(trifluoromethyl)cyclopropyl]-1H-pyrazol-3-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-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-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-[[7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; and A compound selected from [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[6-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone, or a pharmaceutically acceptable salt thereof.

27. 27. A compound of formula (I) according to claim 26, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-5-(trifluoromethyl)pyrazol-4-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-[[1-methyl-5-(trifluoromethyl)pyrazol-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-[[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]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-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)-1H-1,2,4-triazol-3-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-(trifluoromethyl)-1H-1,2,4-triazol-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-[[1-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(trifluoromethyl)-1,2,4-thiadiazol-5-yl]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-(trifluoromethyl)-1,2,4-thiadiazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [7-[[5-(trifluoromethyl)-1H-pyrazol-3-yl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]-[6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.5]nonan-2-yl]methanone; [6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[7-[[5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.5]nonan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[4-(trifluoromethyl)imidazol-1-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-(trifluoromethyl)thiazol-2-yl]methyl]-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]-[6-[[4-[1-(trifluoromethyl)cyclopropyl]pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[1-cyclopropyl-3-(trifluoromethyl)pyrazol-4-yl]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-[[1-cyclopropyl-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-triazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[5-[1-(trifluoromethyl)cyclopropyl]-1H-1,2,4-triazol-3-yl]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-[1-(trifluoromethyl)cyclopropyl]-1H-1,2,4-triazol-3-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-(trifluoromethyl)triazol-1-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-(trifluoromethyl)-1H-pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(trifluoromethyl)-1H-pyrazol-4-yl]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-[[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(3-cyclopropyl-1H-pyrazol-5-yl)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-1H-pyrazol-5-yl)methyl]-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-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)-1,2,4-triazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[4-(trifluoromethyl)-1H-pyrazol-3-yl]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-(trifluoromethyl)-1H-pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-cyclopropyl-3-methyl-pyrazol-1-yl)methyl]-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-5-methyl-pyrazol-1-yl)methyl]-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-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[5-(trifluoromethyl)thiazol-2-yl]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-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-(trifluoromethyl)thiazol-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl]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-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-4-(trifluoromethyl)pyrazol-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-[[1-(2,2,2-trifluoroethyl)pyrazol-4-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-[[3-(difluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]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-(trifluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[2-(2,2,2-trifluoroethyl)triazol-4-yl]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-[[1-(2,2,2-trifluoroethyl)triazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[4-(trifluoromethyl)-1H-imidazol-2-yl]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-(trifluoromethylsulfonimidoyl)pyrazol-1-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-[[2-(2,2,2-trifluoroethyl)triazol-4-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-(trifluoromethyl)-1H-imidazol-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-triflylpyrazol-1-yl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; and A compound selected from [6-[[5-[1-(trifluoromethyl)cyclopropyl]-1H-pyrazol-3-yl]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, or a pharmaceutically acceptable salt thereof.

28. A process for preparing a compound of formula (I) according to any one of claims 1 to 27, or a pharmaceutically acceptable salt thereof, comprising reacting a compound of formula 2; 【Chemistry 109】 (Wherein A and R ３ is as defined in any one of claims 1 to 27) with a compound of formula 1; 【Chemical 110】 (In the formula, R １ , R ２ , B, L, W, Y and Z are as defined in any one of claims 1 to 27) with DMF or CH ３ reacting by heating in a solvent such as CN in the presence of a base such as DIPEA to form said compound of formula (I).

29. 29. A compound of formula (I) according to any one of claims 1 to 27, or a pharmaceutically acceptable salt thereof, when prepared according to the process of claim 28.

30. A compound of formula (I) according to any one of claims 1 to 27, or a pharmaceutically acceptable salt thereof, for use as a therapeutically active substance.

31. A pharmaceutical composition comprising a compound of formula (I) according to any one of claims 1 to 27, or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

32. A method for treating or preventing a disease or disorder associated with monoacylglycerol lipase in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound of formula (I) according to any one of claims 1 to 27, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 31.

33. A compound according to any one of claims 1 to 27, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 31, for use in the method according to claim 32.

34. Use of a compound according to any one of claims 1 to 27, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 31, in a method according to claim 32.

35. 33. Use of a compound according to any one of claims 1 to 27, or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for use in the method according to claim 32.

36. The invention as hereinbefore described.

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