Heterocyclic compounds as inhibitors of monoacylglycerol lipase (MAGL)

Abstract

The present invention provides: a novel heterocyclic compound having the general formula (I) # imgabs0 # wherein A, B, L, W, Y, Z and R1 to R3 are as described herein; comprising the compound; methods of making the compounds; and methods of using the compounds.

Description

Technical Field

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

[0002] Endocannabinoids (ECs) are lipid signals that exert their biological effects by interacting with cannabinoid receptors (CBRs), CB1 and CB2. They regulate multiple physiological processes, including neuroinflammation, neurodegenerative diseases, and tissue regeneration (Iannotti, F. A. et al., Progress in lipid research 2016, 62, 107 - 28.). In the brain, the major 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, D. K. et al., Science 2011, 334, 809). MAGL is expressed throughout the brain and in most brain cell types, including neurons, astrocytes, oligodendrocytes, and microglia (Chanda, P. K. et al., Molecular pharmacology 2010, 78, 996; Viader, A. et al., Cell reports 2015, 12, 798.). Hydrolysis of 2 - AG forms arachidonic acid (AA), which is a precursor of prostaglandins (PGs) and leukotrienes (LTs). The oxidative metabolism of AA increases in inflamed tissues. The inflammatory process involves two major enzymatic reaction pathways of arachidonic acid oxidation, namely 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 products. These products have been detected at the site of inflammation (e.g., in the cerebrospinal fluid of patients with neurodegenerative diseases) and are thought to contribute to the inflammatory response and disease progression. The 2 - AG hydrolase activity in the nervous system of mice lacking MAGL (Mgll - / - ) is significantly reduced, while the 2 - AG level is elevated, while other arachidonic acid - containing phospholipids and neutral lipids, including arachidonoylethanolamine (anandamide, AEA) and other free fatty acids, remain unchanged. In contrast, the levels of AA - derived and AA - derived prostaglandins and other eicosanoids, including prostaglandin E2 (PGE2), D2 (PGD2), F2 (PGF2), and thromboxane B2 (TXB2), are greatly reduced. Phospholipase A 2 (PLA 2 ) has been regarded as the major source of AA, but the AA level remains unchanged in the brains of cPLA 2 -deficient mice, thus enhancing the key role of MAGL in AA production and the regulation of the brain inflammatory process.

[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 mental disorders such as anxiety and migraine). In the brain, the production of eicosanoids and prostaglandins controls the neuroinflammatory process. The pro-inflammatory agent lipopolysaccharide (LPS) causes a stable time-dependent increase in brain eicosanoid production, which is significantly attenuated in Mgll- / - mice. LPS treatment also causes a general increase in pro-inflammatory cytokines (including interleukin-1-α (IL-1-α), IL-1β, IL-6) and tumor necrosis factor-α (TNF-α), which are inhibited in Mgll- / - mice).

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

[0005] In addition, genetic and / or pharmacological disruption of MAGL activity has been shown to have a protective effect in animal models of various neurodegenerative diseases, 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 neurodegenerative diseases (Long, J.Z. et al., Nature chemical biology 2009, 5, 37.). Systemic injection of such inhibitors recapitulates the Mgll- / - mouse phenotype in the brain, including increased 2-AG levels, decreased AA levels, and associated eicosanoid production, and prevents cytokine production and microglial activation after LPS-induced neuroinflammation (Nomura, D.K. et al., Science 2011, 334, 809.), fully confirming MAGL as a drug target.

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

[0007] In addition, oligodendrocytes (OLs), the myelin-forming cells of 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. The pharmacological inhibition of both cannabinoids and MAGL has been reported to attenuate the excitotoxic seizure vulnerability of OLs and OPCs and thus may have neuroprotective effects (Bernal-Chico, A. et al., Glia 2015, 63, 163.). In addition, pharmacological inhibition of MAGL increases the number of myelin-forming OLs in the mouse brain, indicating that MAGL inhibition promotes the differentiation of OPCs into myelin-forming OLs in vivo (Alpar, A. et al., Nature communications 2014, 5, 4421.). In a mouse model of progressive multiple sclerosis, inhibition of MAGL also promotes myelin regeneration and functional recovery (Feliu A. et al., Journal of Neuroscience 2017, 37(35), 8385.).

[0008] In recent years, metabolism, especially lipid metabolism, has received great attention in cancer research. Researchers believe that de novo fatty acid synthesis plays an important role in tumor development. Many studies have shown that endogenous cannabinoids have anti-tumor effects, including anti-proliferative, apoptosis-inducing, and anti-metastatic effects. MAGL, as an important catabolic enzyme in lipid metabolism and the endogenous cannabinoid system, and as a component of the gene expression signature, affects different aspects of tumorigenesis, including malignant gliomas (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 pathophysiological effects (Marquez, Suarez et al. 2009). All these effects are mainly driven via cannabinoid receptors (CBRs), CB1 and CB2. CB1 receptors are present throughout the GI tract in animals and healthy humans, especially in the enteric nervous system (ENS) and the epithelial lining, as well as in the smooth muscle cells of blood vessels in the colon wall (Wright, Rooney et al. 2005), (Duncan, Davison et al. 2005). Activation of CB1 produces antiemetic, antiperistaltic, and anti-inflammatory effects and contributes to the regulation of pain (Perisetti, Rimu et al. 2020). CB2 receptors are expressed in immune cells (such as plasma cells and macrophages) in the lamina propria of the GI tract (Wright, Rooney et al. 2005) and act mainly on the epithelium of human colon tissue associated with inflammatory bowel disease (IBD). Activation of CB2 exerts an anti-inflammatory effect by reducing pro-inflammatory cytokines. The expression of MAGL in colon tissue of UC patients is increased (Marquez, Suarez et al. 2009), and the level of 2-AG in plasma of IBD patients is increased (Grill, Hogenauer et al. 2019). Several animal studies have confirmed the potential of MAGL inhibitors for the symptomatic treatment of IBD. MAGL inhibition prevents TNBS-induced colitis in mice and reduces local circulating inflammatory markers via the CB1 / CB2 MoA (Marquez, Suarez et al. 2009). In addition, MAGL inhibition improves intestinal wall integrity and intestinal permeability via a CB1-driven MoA (Wang, Zhang et al. 2020).

[0010] In summary, inhibiting the action and / or activation of MAGL is a promising novel therapeutic strategy for the treatment or prevention of neuroinflammation, neurodegenerative diseases, pain, cancer, mental disorders, inflammatory bowel disease, abdominal pain, and abdominal pain associated with irritable bowel syndrome. In addition, inhibiting the action and / or activation of MAGL is a promising new therapeutic strategy for providing neuroprotection and myelin regeneration. Therefore, there is an urgent unmet medical need for novel MAGL inhibitors. Summary of the Invention

[0011] In a first aspect, the present invention provides a compound of formula (I)

[0012]

[0013] wherein A, B, L, W, Y, Z, and R 1 to R 3 are as defined herein.

[0014] 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

[0015] Definition

[0016] Features, integers, characteristics, compounds, chemical moieties or groups described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein unless incompatible therewith. All features disclosed in this specification (including any accompanying claims, abstract and drawings) and / or all steps of any method or process disclosed thereby may be combined in any combination, except for combinations in which at least some of these features and / or steps are mutually exclusive. The invention is not limited to the details of any foregoing embodiments. The invention extends to any novel feature or any novel combination of features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel step or any novel combination of steps of any method or process disclosed thereby.

[0017] The term "alkyl" refers to a group of 1 to 6 carbon atoms ("C 1-6 -alkyl" (e.g., 1, 2, 3, 4, 5 or 6 carbon atoms) of a monovalent or polyvalent (e.g., monovalent or divalent) straight or branched saturated hydrocarbon group. In some embodiments, the alkyl group contains 1 to 4 carbon atoms, such as 1, 2, 3 or 4 carbon atoms. In other embodiments, the alkoxy group contains 1 to 3 carbon atoms. Some non-limiting examples of alkyl include methyl, ethyl, propyl, 2-propyl (isopropyl), n-butyl, isobutyl, sec-butyl, tert-butyl and 2,2-dimethylpropyl. Particularly preferred but non-limiting examples of alkyl are methyl, tert-butyl and 2,2-dimethylpropyl.

[0018] The term "alkoxy" refers to an alkyl group as defined above 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, such as 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.

[0019] 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 cycloalkylalkyl is cyclopropylmethyl.

[0020] The term "halogen" or "halo" means fluorine (F), chlorine (Cl), bromine (Br) or iodine (I). Preferably, the term "halogen" or "halo" means fluorine (F), chlorine (Cl) or bromine (Br). Particularly preferred but non-limiting examples of "halogen" or "halo" are fluorine (F) and chlorine (Cl).

[0021] As used herein, the term "cycloalkyl" means a saturated monocyclic or bicyclic hydrocarbon group having from 3 to 10 ring carbon atoms ("C 3-10 -cycloalkyl"). In some preferred embodiments, the cycloalkyl group is a monocyclic hydrocarbon group having from 3 to 8 ring carbon atoms. "Bicyclic cycloalkyl" means a cycloalkyl moiety consisting of two saturated carbon rings having two common carbon atoms (i.e., the bridge separating the two rings is a single bond or a chain of one or two ring atoms) and a spiro moiety (i.e., the two rings are connected via a common ring atom). Preferably, the cycloalkyl group is a monocyclic hydrocarbon group having 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]pentyl, norbornyl and 1-bicyclo[2.2.2]octyl. A particularly preferred but non-limiting example of cycloalkyl is cyclopropyl.

[0022] The term "aryl" means a monocyclic, bicyclic or tricyclic carbocyclic system having a total of 6 to 14 ring members ("C 6 -C 14 -aryl"), preferably 6 to 12 ring members and more preferably 6 to 10 ring members, and wherein at least one ring in the system is aromatic. Some non-limiting examples of aryl include phenyl and 9H-fluorenyl (e.g., 9H-fluoren-9-yl). Particularly preferred but non-limiting examples of aryl are phenyl.

[0023] The term "hydroxy" means the –OH group.

[0024] The term "cyano" means the –CN (nitrile) group.

[0025] The term "sulfamoyl" means the group H 2 N-SO 2 –.

[0026] The term "haloalkyl" means an alkyl group as defined herein, wherein at least one of the hydrogen atoms of the alkyl group has been replaced by a halogen atom (preferably fluorine). Preferably, "haloalkyl" means an alkyl group in which 1, 2 or 3 hydrogen atoms of the alkyl group have been replaced by halogen atoms, most preferably fluorine. Particularly preferred but non-limiting examples of haloalkyl are trifluoromethyl, difluoromethyl, 1,1-difluoroethyl, 2,2-difluoroethyl and 2,2,2-trifluoroethyl.

[0027] The term "halocycloalkyl" refers to a cycloalkyl group as defined herein, wherein at least one of the hydrogen atoms of the cycloalkyl group has been replaced by a halogen atom (preferably fluorine). Preferably, "halocycloalkyl" refers to a cycloalkyl group in which 1, 2 or 3 hydrogen atoms of the cycloalkyl group have been replaced by a halogen atom, most preferably fluorine. Particularly preferred but non-limiting examples of halocycloalkyl are 1-fluorocyclopropyl and 2,2-difluorocyclopropyl.

[0028] The term "hydroxycycloalkyl" refers to a cycloalkyl group as defined herein, wherein at least one hydrogen atom has been replaced by a hydroxy group. Preferably, "hydroxycycloalkyl" refers to a cycloalkyl group in which 1, 2 or 3 hydrogen atoms of the cycloalkyl group have been replaced by a hydroxy group. Particularly preferred but non-limiting examples of hydroxycycloalkyl are 1-hydroxycyclopropyl.

[0029] The term "haloalkylcycloalkyl" refers to a cycloalkyl group as defined herein, wherein at least one of the hydrogen atoms of the cycloalkyl group has been replaced by a haloalkyl group. In some embodiments, "haloalkylcycloalkyl" refers to a cycloalkyl group in which 1, 2 or 3 hydrogen atoms of the cycloalkyl group have been replaced by a haloalkyl group. Preferably, "haloalkylcycloalkyl" refers to a cycloalkyl group in which 1 to 2 hydrogen atoms of the cycloalkyl group have been replaced by a haloalkyl group. Particularly preferred but non-limiting examples of haloalkylcycloalkyl are 1-(trifluoromethyl)cyclopropyl and 2-(trifluoromethyl)cyclopropyl.

[0030] The term "haloalkoxy" refers to an alkoxy group as defined herein, wherein at least one of the hydrogen atoms of the alkoxy group has been replaced by a halogen atom (preferably fluorine). Preferably, "haloalkoxy" refers to an alkoxy group in which 1, 2 or 3 hydrogen atoms of the alkoxy group have been replaced by a halogen atom, most preferably fluorine. 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.

[0031] The term "pharmaceutically acceptable salts" refers to those salts which retain the biological effectiveness and properties of the free bases or free acids and which are not biologically or otherwise undesirable. These salts are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc. (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, N-acetylcysteine, etc. Additionally, these salts can be prepared by adding an inorganic base or an organic base to the free acid. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium salts, etc. 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, etc.).

[0032] The compounds of formula (I) can contain several asymmetric centers and can exist as optically pure enantiomers, mixtures of enantiomers (e.g., racemates), optically pure diastereomers, mixtures of diastereomers, diastereomeric racemates or mixtures of diastereomeric racemates.

[0033] According to the Cahn-Ingold-Prelog Convention, an asymmetric carbon atom can be of the "R" or "S" configuration.

[0034] The abbreviation "MAGL" refers to monoacylglycerol lipase. The terms "MAGL" and "monoacylglycerol lipase" are used interchangeably herein.

[0035] As used herein, the term "treatment" includes: (1) inhibiting the state, condition or disease of at least one clinical or subclinical symptom of a disease (e.g., in the case of maintenance treatment, preventing, alleviating or delaying the development or recurrence of the disease); and / or (2) alleviating the condition (i.e., causing the state, condition or disease or at least one clinical or subclinical symptom to regress). The benefit to the patient to be treated is statistically significant or at least perceptible to the patient or the physician. However, it should be understood that when a drug is administered to a patient to treat a disease, the result may not always be an effective treatment.

[0036] As used herein, the term "prophylaxis" includes: preventing or delaying the appearance of clinical symptoms of a state, condition or disease which develops in a mammal, especially in a human, who may be susceptible to or predisposed to that state, condition or disease but has not yet experienced or shown clinical or subclinical symptoms of that state, condition or disease.

[0037] As used herein, the term "neuroinflammation" refers to acute and chronic inflammation of neural tissue, which is the main tissue component of two parts of the nervous system; the brain and spinal cord of the central nervous system (CNS) and the peripheral nerves that are branches of the peripheral nervous system (PNS). Chronic neuroinflammation is associated with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Acute neuroinflammation usually occurs immediately after injury to the central nervous system, for example, caused by traumatic brain injury (TBI).

[0038] As used herein, the term "traumatic brain injury" ("TBI", also known as "intracranial injury") refers to brain injury caused by external mechanical forces such as rapid acceleration or deceleration, impact, shock wave, or projectile penetration.

[0039] As used herein, the term "neurodegenerative disease" refers to a disease associated with the progressive loss of the structure or function of neurons (including neuron death). Examples of neurodegenerative diseases include, but are not limited to, multiple sclerosis, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.

[0040] As used herein, the term "mental disorder" (also known as mental illness or psychiatric disorder) refers to behavioral or mental patterns that may cause distress or poor quality of life. Such characteristics may be persistent, recurrent, or remitting, or may be a single event. Examples of mental disorders include, but are not limited to, anxiety disorders and depression.

[0041] As used herein, the term "pain" refers to an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Examples of pain include, but are not limited to, nociceptive pain, chronic pain (including idiopathic pain), neuropathic pain (including chemotherapy-induced neuropathy), phantom pain, and psychogenic pain. A specific example of pain is neuropathic pain, which is caused by damage or disease affecting any part of the nervous system (i.e., the somatosensory system) involved in body sensation. In one embodiment, "pain" is neuropathic pain caused by amputation or thoracotomy. In one embodiment, "pain" is chemotherapy-induced neuropathy.

[0042] As used herein, the term "neurotoxicity" refers to the toxicity of the nervous system. This occurs upon exposure to natural or man-made toxic substances (neurotoxins) that alter the normal activity of the nervous system, thereby causing damage to neural tissue. Examples of neurotoxicity include, but are not limited to, neurotoxicity caused by exposure to chemotherapy, radiotherapy, drug therapy, drug abuse, and substances used in organ transplantation, as well as exposure to heavy metals, certain foods and food additives, pesticides, industrial and / or cleaning solvents, cosmetics, and some natural substances.

[0043] As used herein, the term "cancer" refers to a disease characterized by the presence of a neoplasm or tumor resulting from the growth of abnormally uncontrolled cells (such cells being "cancer cells"). As used herein, the term cancer expressly includes, but is not limited to, hepatocellular carcinoma, colon carcinoma, and ovarian cancer.

[0044] As used herein, the term "mammal" includes humans and non-humans, and includes, but is not limited to, humans, non-human primates, dogs, cats, rats, cows, horses, and pigs. In a particularly preferred embodiment, the term "mammal" refers to humans.

[0045] Compounds of the present invention

[0046] In a first aspect, the present invention provides a compound of formula (I)

[0047]

[0048] or a pharmaceutically acceptable salt thereof, wherein:

[0049] W and Z are each independently selected from CH 2 and CH 2 CH 2 ;

[0050] Y is selected from CH and N;

[0051] U is selected from CH and N;

[0052] V is selected from NH, O, and S;

[0053] X is selected from NH and O;

[0054] L is selected from CH 2 and O;

[0055] A is selected from:

[0056]

[0057] B is selected from: and a 9-membered fused bicyclic heteroaryl group containing 1 to 3 heteroatoms selected from N, O, and S, the remaining ring atoms being carbon;

[0058] R 1 is selected from 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-C3 -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 and (C 1 -C 6 -alkyl) 2 PO-;

[0059] R 1a is selected from C 1 -C 6 -alkyl and halo-C 1 -C 6 -alkyl;

[0060] R 2 is selected from 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

[0061] R 3 is selected from 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 -alkoxy.

[0062] In one embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof, wherein:

[0063] W and Z are each independently selected from CH 2 and CH 2 CH 2 ;

[0064] Y is selected from CH and N;

[0065] U is selected from CH and N;

[0066] V is selected from NH, O and S;

[0067] L is selected from CH 2 and O;

[0068] A is selected from:

[0069]

[0070] B is selected from:

[0071]

[0072] R 1 is selected from 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 and (C 1 -C 6 -alkyl) 2 PO-;

[0073] R 2 is selected from 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

[0074] R 3 is selected from C 3 -C 10 -cycloalkyl, hydroxy-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 -alkoxy.

[0075] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof, wherein both W and Z are CH 2 .

[0076] In one embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof, wherein both W and Z are CH 2 CH 2 .

[0077] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof, wherein Y is CH.

[0078] 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.

[0079] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof, wherein

[0080] both W and Z are CH 2 ; or

[0081] both W and Z are CH 2 CH 2 ; and

[0082] Y is selected from CH and N.

[0083] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof, wherein

[0084] both W and Z are CH 2 ; and

[0085] Y is CH.

[0086] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is selected from:

[0087]

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

[0089]

[0090] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is selected from:

[0091]

[0092] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is selected from:

[0093]

[0094] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is selected from:

[0095]

[0096] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is selected from:

[0097]

[0098] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is

[0099] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is

[0100] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is

[0101] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein L is CH 2 .

[0102] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein A is selected from

[0103] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein A is

[0104] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein A is

[0105] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein:

[0106] R 1 is selected from 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, the group and (C 1 -C 6 -alkyl) 2 PO-;

[0107] R 1a is selected from C 1 -C 6 -alkyl and halo-C 1 -C 6 -alkyl; and

[0108] X is selected from NH and O.

[0109] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein:

[0110] R 1 is selected from hydrogen, methyl, ethyl, tert-butyl, cyano, CHF 2 ,CF 3, 1,1-difluoroethyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, sulfamoyl, dimethylphosphoryl, phenyl and (CF 3 ) cyclopropyl;

[0111] R 1a is selected from methyl and CF 3 ; and

[0112] X is selected from NH and O.

[0113] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof, wherein:

[0114] R 1 is selected from halo-C 1 -C 6 -alkyl, C 3 -C 10 -cycloalkyl, halo-C 1 -C 6 -alkyl-C 3 -C 10 -cycloalkyl and the group

[0115] R 1a is halo-C 1 -C 6 -alkyl; and

[0116] X is selected from NH and O.

[0117] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof, wherein:

[0118] R 1 is selected from CHF 2 、CF 3 、2,2,2-trifluoroethyl, cyclopropyl, (CF 3 ) cyclopropyl and the group

[0119] R 1a is CF 3 ; and

[0120] X is selected from NH and O.

[0121] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof, wherein:

[0122] R 1 is selected from CF 3 、cyclopropyl, (CF 3 ) cyclopropyl and the group

[0123] R 1a is CF 3 ; and

[0124] X is selected from NH and O.

[0125] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 1 is selected from 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 and (C 1 -C 6 -alkyl) 2 PO-.

[0126] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 1 is selected from hydrogen, methyl, ethyl, tert-butyl, cyano, CHF 2 , CF 3 , 1,1-difluoroethyl, 2,2,2-trifluoroethyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, sulfamoyl, dimethylphosphoryl, phenyl and (CF 3 ) cyclopropyl.

[0127] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 1 is selected from halo-C 1 -C 6 -alkyl, C 3 -C 10 -cycloalkyl and halo-C 1 -C 6 -alkyl-C 3 -C 10 -cycloalkyl.

[0128] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R1 Selected from CHF 2 , CF 3 , 2,2,2-trifluoroethyl, cyclopropyl and (CF 3 ) cyclopropyl.

[0129] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 1 is selected from CF 3 , cyclopropyl and 1-(trifluoromethyl)cyclopropyl.

[0130] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 1 is halo-C 1 -C 6 -alkyl.

[0131] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 1 is CF 3 .

[0132] In an embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 2 is selected from hydrogen, C 1 -C 6 -alkyl and halo-C 1 -C 6 -alkyl.

[0133] In an embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 2 is selected from hydrogen, methyl, ethyl and CF 3 .

[0134] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 2 is selected from hydrogen, methyl and CF 3 .

[0135] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 2 is hydrogen.

[0136] In an embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 3 is selected from C 3 -C 10 -cycloalkyl, hydroxy-C 3 -C 10 -cycloalkyl, amino-C3 -C 10 -cycloalkyl and halo-C 1 -C 6 -alkyl.

[0137] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 3 is selected from cyclopropyl, 1-hydroxycyclopropyl, 1-aminocyclopropyl, and CF 3 .

[0138] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 3 is selected from C 3 -C 10 -cycloalkyl, hydroxy-C 3 -C 10 -cycloalkyl, halo-C 1 -C 6 -alkyl.

[0139] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 3 is selected from C 3 -C 10 -cycloalkyl and halo--C 1 -C 6 -alkyl.

[0140] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 3 is selected from cyclopropyl, hydroxycyclopropyl, and CF 3 .

[0141] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 3 is selected from cyclopropyl and CF 3 .

[0142] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 3 is C 3 -C 10 -cycloalkyl.

[0143] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 3 is cyclopropyl.

[0144] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 3For CF 3 .

[0145] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein:

[0146] W and Z are each independently selected from CH 2 and CH 2 CH 2 ;

[0147] Y is selected from CH and N;

[0148] U is selected from CH and N;

[0149] V is selected from NH, O and S;

[0150] X is selected from NH and O;

[0151] L is selected from CH 2 and O;

[0152] A is selected from

[0153] B is selected from:

[0154]

[0155] R 1 is selected from 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 and (C 1 -C 6 -alkyl) 2 PO-;

[0156] R 1a is selected from C 1 -C 6 -alkyl and halo-C 1 -C 6 -alkyl;

[0157] R 2Selected from hydrogen, C 1 -C 6 -alkyl and halo-C 1 -C 6 -alkyl; and

[0158] R 3 Selected from C 3 -C 10 -cycloalkyl, hydroxy-C 3 -C 10 -cycloalkyl, amino-C 3 -C 10 -cycloalkyl, halo-C 1 -C 6 -alkyl.

[0159] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof, wherein:

[0160] Both W and Z are CH 2 ; or

[0161] Both W and Z are CH 2 CH 2 ;

[0162] Y is selected from CH and N;

[0163] X is selected from NH and O;

[0164] L is CH 2 ;

[0165] A is selected from

[0166] B is selected from:

[0167]

[0168] R 1 Selected from halo-C 1 -C 6 -alkyl, C 3 -C 10 -cycloalkyl, halo-C 1 -C 6 -alkyl-C 3 -C 10 -cycloalkyl and the group

[0169] R 1a is halo-C 1 -C 6 -alkyl;

[0170] R 2 Selected from hydrogen, C 1 -C6 -alkyl and halo-C 1 -C 6 -alkyl; and

[0171] R 3 is selected from C 3 -C 10 -cycloalkyl, hydroxy-C 3 -C 10 -cycloalkyl, halo-C 1 -C 6 -alkyl.

[0172] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein:

[0173] Both W and Z are CH 2 ; or

[0174] Both W and Z are CH 2 CH 2 ;

[0175] Y is selected from CH and N;

[0176] X is selected from NH and O;

[0177] L is CH 2 ;

[0178] A is selected from

[0179] B is selected from:

[0180]

[0181] R 1 is selected from CHF 2 、CF 3 、2,2,2-trifluoroethyl, cyclopropyl, (CF 3 ) cyclopropyl and the group

[0182]

[0183] R 1a is CF 3 ;

[0184] R 2 is selected from hydrogen, methyl and CF 3 ; and

[0185] R 3 is selected from cyclopropyl, hydroxycyclopropyl and CF 3 .

[0186] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein:

[0187] W and Z are each independently selected from CH 2 and CH 2 CH 2 ;

[0188] Y is selected from CH and N;

[0189] U is selected from CH and N;

[0190] V is selected from NH, O and S;

[0191] L is selected from CH 2 and O;

[0192] A is selected from

[0193] B is selected from:

[0194]

[0195] R 1 is selected from 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 and (C 1 -C 6 -alkyl) 2 PO-;

[0196] R 2 is selected from hydrogen, C 1 -C 6 -alkyl and halo-C 1 -C 6 -alkyl; and

[0197] R 3 is selected from C 3 -C 10 -cycloalkyl, hydroxy-C 3 -C 10 -cycloalkyl, halo-C1 -C 6 -alkyl

[0198] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein:

[0199] both W and Z are CH 2 ; or

[0200] both W and Z are CH 2 CH 2 ;

[0201] Y is selected from CH and N;

[0202] L is CH 2 ;

[0203] A is selected from

[0204] B is selected from:

[0205]

[0206] R 1 is selected from halo-C 1 -C 6 -alkyl, C 3 -C 10 -cycloalkyl, and halo-C 1 -C 6 -alkyl-C 3 -C 10 -cycloalkyl;

[0207] R 2 is selected from hydrogen, C 1 -C 6 -alkyl, and halo-C 1 -C 6 -alkyl; and

[0208] R 3 is selected from C 3 -C 10 -cycloalkyl, hydroxy-C 3 -C 10 -cycloalkyl, halo-C 1 -C 6 -alkyl.

[0209] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein:

[0210] both W and Z are CH 2 ; or

[0211] both W and Z are CH2 CH 2 ;

[0212] Y is selected from CH and N;

[0213] L is CH 2 ;

[0214] A is selected from

[0215] B is selected from:

[0216]

[0217] R 1 is selected from CHF 2 , CF 3 , 2,2,2-trifluoroethyl, cyclopropyl and (CF 3 ) cyclopropyl;

[0218] R 2 is selected from hydrogen, methyl and CF 3 ; and

[0219] R 3 is selected from cyclopropyl, hydroxycyclopropyl and CF 3 .

[0220] 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:

[0221] [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;

[0222] [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;

[0223] [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;

[0224] [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;

[0225] [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;

[0226] [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;

[0227] [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;

[0228] [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;

[0229] [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;

[0230] [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;

[0231] [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;

[0232] [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;

[0233] [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;

[0234] [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;

[0235] [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;

[0236] [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;

[0237] [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;

[0238] [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;

[0239] [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;

[0240] [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;

[0241] [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;

[0242] [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;

[0243] [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;

[0244] [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;

[0245] [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;

[0246] [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;

[0247] [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;

[0248] [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;

[0249] [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;

[0250] [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;

[0251] [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;

[0252] [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;

[0253] [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;

[0254] [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;

[0255] [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;

[0256] [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;

[0257] 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;

[0258] 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;

[0259] [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;

[0260] [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;

[0261] [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;

[0262] [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;

[0263] [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;

[0264] [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;

[0265] [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;

[0266] [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;

[0267] [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;

[0268] [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;

[0269] [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;

[0270] [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;

[0271] [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;

[0272] [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;

[0273] [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;

[0274] [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;

[0275] [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;

[0276] [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;

[0277] [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;

[0278] [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;

[0279] [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;

[0280] [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;

[0281] [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;

[0282] [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;

[0283] [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;

[0284] [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;

[0285] [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;

[0286] [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;

[0287] [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;

[0288] [6-[[5-Methyl-3-(trifluoromethyl)-1H-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;

[0289] [6-(3-Cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[0290] [6-[3-(1-Hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[0291] [6-[[3-Methyl-5-(trifluoromethyl)-1H-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;

[0292] [6-(3-Cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-methyl-5-(trifluoromethyl)-1H-pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[0293] [6-[3-(1-Hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-methyl-5-(trifluoromethyl)-1H-pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[0294] [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;

[0295] [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;

[0296] [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;

[0297] [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;

[0298] [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;

[0299] [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;

[0300] [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;

[0301] [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;

[0302] [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;

[0303] [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;

[0304] [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;

[0305] [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;

[0306] [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;

[0307] [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;

[0308] [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;

[0309] [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;

[0310] [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;

[0311] [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;

[0312] [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;

[0313] [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;

[0314] [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;

[0315] [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;

[0316] [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;

[0317] [6-[(4-tert-Butyl-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;

[0318] [6-[(4-tert-Butyl-oxazol-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;

[0319] [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;

[0320] [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;

[0321] [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;

[0322] [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;

[0323] [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;

[0324] [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;

[0325] [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;

[0326] [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;

[0327] [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;

[0328] [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-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone;

[0329] [6-[[1-(2,2,2-Trifluoroethyl)-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;

[0330] [6-(3-Cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone;

[0331] [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)-1H-pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone;

[0332] [6-[[3-Methyl-1-(2,2,2-trifluoroethyl)-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;

[0333] [6-(3-Cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[3-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone;

[0334] [6-[[5-Methyl-1-(2,2,2-trifluoroethyl)-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;

[0335] [6-(3-Cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[5-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone;

[0336] [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;

[0337] [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;

[0338] [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;

[0339] [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;

[0340] [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;

[0341] [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;

[0342] [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;

[0343] [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;

[0344] [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;

[0345] [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;

[0346] [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;

[0347] [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;

[0348] [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;

[0349] [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;

[0350] [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;

[0351] [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;

[0352] [6-[(5-Cyclopropyl-3-methylpyrazol-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;

[0353] [6-[(5-Cyclopropyl-3-methylpyrazol-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;

[0354] [6-[(3-Cyclopropyl-5-methylpyrazol-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;

[0355] [6-[(3-Cyclopropyl-5-methylpyrazol-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;

[0356] [6-[(3-Cyclopropyl-5-methylpyrazol-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;

[0357] [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;

[0358] [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;

[0359] [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;

[0360] [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;

[0361] [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;

[0362] [6-[(3-cyclopropylpyrazol-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;

[0363] [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;

[0364] [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;

[0365] [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;

[0366] [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;

[0367] [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;

[0368] [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;

[0369] [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;

[0370] [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;

[0371] [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;

[0372] [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;

[0373] [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;

[0374] [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;

[0375] [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;

[0376] [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;

[0377] [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;

[0378] [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;

[0379] [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;

[0380] [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;

[0381] [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;

[0382] [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;

[0383] [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;

[0384] [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;

[0385] [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;

[0386] [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;

[0387] [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;

[0388] [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;

[0389] [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;

[0390] [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;

[0391] [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;

[0392] [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;

[0393] [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;

[0394] [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;

[0395] [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;

[0396] [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;

[0397] [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;

[0398] [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;

[0399] [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;

[0400] [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;

[0401] [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;

[0402] [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;

[0403] [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;

[0404] [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;

[0405] [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;

[0406] [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;

[0407] [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;

[0408] [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;

[0409] [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;

[0410] [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;

[0411] [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;

[0412] [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;

[0413] [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;

[0414] [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;

[0415] [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;

[0416] [6-(3-Cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(2,2,2-trifluoroethyl)-1,2,4-triazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone;

[0417] [6-[[1-(2,2,2-trifluoroethyl)-1H-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;

[0418] [6-(3-Cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(2,2,2-trifluoroethyl)-1H-tetrazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone;

[0419] [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;

[0420] [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;

[0421] [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;

[0422] [6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(2,2,2-trifluoroethyl)-1,2,4-triazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[0423] [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;

[0424] [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;

[0425] [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;

[0426] [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;

[0427] [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;

[0428] [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;

[0429] [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;

[0430] [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;

[0431] [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;

[0432] [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;

[0433] [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;

[0434] [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;

[0435] [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;

[0436] [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;

[0437] [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;

[0438] [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;

[0439] [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;

[0440] [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;

[0441] [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;

[0442] [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;

[0443] [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;

[0444] [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;

[0445] [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;

[0446] [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;

[0447] [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;

[0448] [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;

[0449] [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;

[0450] [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;

[0451] [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;

[0452] [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;

[0453] [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;

[0454] [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;

[0455] [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;

[0456] [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;

[0457] [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;

[0458] [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;

[0459] [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;

[0460] [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;

[0461] [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;

[0462] [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;

[0463] [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;

[0464] [6-(3-Cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-methyl-5-(trifluoromethyl)-1,2,4-triazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone;

[0465] [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;

[0466] [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;

[0467] [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;

[0468] [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;

[0469] [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;

[0470] 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;

[0471] 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;

[0472] [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;

[0473] [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;

[0474] [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-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[0475] [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;

[0476] [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;

[0477] [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;

[0478] [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;

[0479] [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;

[0480] [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;

[0481] [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;

[0482] [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;

[0483] [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;

[0484] [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;

[0485] [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;

[0486] [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;

[0487] [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;

[0488] [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;

[0489] [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;

[0490] [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;

[0491] [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;

[0492] [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;

[0493] [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;

[0494] [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;

[0495] [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;

[0496] [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;

[0497] [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;

[0498] [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;

[0499] [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;

[0500] 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;

[0501] 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;

[0502] 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;

[0503] [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;

[0504] [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;

[0505] [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;

[0506] [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;

[0507] [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;

[0508] [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;

[0509] [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;

[0510] [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;

[0511] [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;

[0512] [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;

[0513] [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;

[0514] [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;

[0515] [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;

[0516] [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;

[0517] [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;

[0518] [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;

[0519] [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;

[0520] [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;

[0521] [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;

[0522] [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;

[0523] [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;

[0524] [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;

[0525] [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;

[0526] [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;

[0527] [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;

[0528] [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;

[0529] [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;

[0530] [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;

[0531] [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;

[0532] [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;

[0533] [6-[3-(1-Hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-methylsulfonylpyrazol-1-yl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[0534] [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;

[0535] [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;

[0536] [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;

[0537] [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;

[0538] [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;

[0539] [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;

[0540] [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;

[0541] [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;

[0542] [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;

[0543] [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;

[0544] [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;

[0545] [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;

[0546] [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;

[0547] [6-[(4-Methylsulfonylpyrazol-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;

[0548] [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;

[0549] [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;

[0550] [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;

[0551] [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;

[0552] [6-(3-Cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-methylsulfonylpyrazol-1-yl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[0553] [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;

[0554] [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;

[0555] [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;

[0556] [6-[[1-(2,2,2-Trifluoroethyl)-1,2,4-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;

[0557] [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;

[0558] [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;

[0559] [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;

[0560] [6-[[2-(2,2,2-Trifluoroethyl)-1,2,4-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;

[0561] [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;

[0562] [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;

[0563] [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;

[0564] [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;

[0565] [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;

[0566] [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;

[0567] [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-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[0568] [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;

[0569] [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;

[0570] [6-(3-Cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(2,2,2-trifluoroethyl)-1,2,4-triazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[0571] [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;

[0572] [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;

[0573] [6-[3-(Trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-trifluoromethanesulfonylpyrazol-1-yl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[0574] [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;

[0575] [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;

[0576] [6-(3-Cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-trifluoromethanesulfonylpyrazol-1-yl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[0577] [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;

[0578] [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;

[0579] [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

[0580] [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.

[0581] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein the compound of formula (I) is selected from:

[0582] [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;

[0583] [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;

[0584] [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;

[0585] [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;

[0586] [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;

[0587] [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;

[0588] [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;

[0589] [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;

[0590] [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;

[0591] [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;

[0592] [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;

[0593] [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;

[0594] [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;

[0595] [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;

[0596] [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;

[0597] [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;

[0598] [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;

[0599] [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;

[0600] [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;

[0601] [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;

[0602] [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;

[0603] [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;

[0604] [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;

[0605] [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;

[0606] [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;

[0607] [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;

[0608] [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;

[0609] [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;

[0610] [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;

[0611] [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;

[0612] [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;

[0613] [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;

[0614] [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;

[0615] [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;

[0616] [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;

[0617] [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;

[0618] [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;

[0619] [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;

[0620] [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;

[0621] [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;

[0622] [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;

[0623] [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;

[0624] [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;

[0625] [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-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[0626] [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;

[0627] [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;

[0628] [6-(3-Cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(2,2,2-trifluoroethyl)-1,2,4-triazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[0629] [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;

[0630] [6-[3-(Trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[(4-trifluoromethanesulfonylpyrazol-1-yl)methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; and

[0631] [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.

[0632] 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 [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.

[0633] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein the 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.

[0634] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein the 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.

[0635] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein the 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.

[0636] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein the 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.

[0637] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein the 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.

[0638] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein the 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.

[0639] In one particular embodiment, the present invention provides a pharmaceutically acceptable salt of a compound of formula (I) as described herein. In another particular embodiment, the present invention provides a compound of formula (I) as a free base as described herein.

[0640] In some embodiments, the compounds of formula (I) are isotopically labeled by replacing one or more atoms thereof with atoms having a different atomic mass or mass number. Such isotopically labeled (i.e., radiolabeled) compounds of formula (I) are considered to be within the scope of the present disclosure. Examples of isotopes that can be incorporated into the compounds of formula (I) include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, and iodine, such as, but not limited to 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 I. Certain isotopically labeled compounds of formula (I) (e.g., those containing a radioactive isotope) can be used in drug and / or substrate tissue distribution studies. The radioactive isotopes tritium (i.e., 3 H) and carbon-14 (i.e., 14 C) are particularly useful in this regard because they are readily incorporated and means for detection are readily available. For example, the compounds of formula (I) can be enriched with 1, 2, 5, 10, 25, 50, 75, 90, 95, or 99% of a given isotope.

[0641] Replacement with a heavier isotope such as deuterium (i.e., 2 H) can provide certain therapeutic advantages due to greater metabolic stability, e.g., increased in vivo half-life or reduced dosage requirements.

[0642] Replacement with a positron emitting isotope such as 11 C, 18 F, 15 O, and 13 N) can be used in positron emission tomography (PET) studies to examine 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 similar to those described in the examples set forth below using appropriate isotopically labeled reagents in place of the previously used unlabeled reagents.

[0643] Preparation process

[0644] The preparation of the compounds of formula (I) according to the present invention can be carried out according to sequential or concurrent synthetic routes. The synthesis of the present invention is shown in the following general scheme. The skills required to carry out the reactions and purify the resulting products are known to those skilled in the art. Unless indicated to the contrary, the substituents and indices used in the following method descriptions have the meanings provided herein.

[0645] If one of the starting materials, intermediates or compounds of formula (I) contains one or more functional groups that are unstable or reactive under the reaction conditions of one or more reaction steps, appropriate protecting groups (as described in "Protective Groups in Organic Chemistry" 5th Edition, 2014, John Wiley & Sons, N.Y. by T.W. Greene and P.G.M. Wutts) can be introduced before the key steps where methods well known in the art are applied. Such protecting groups can be removed using standard methods described in the literature at a later stage of the synthesis.

[0646] If the starting material or intermediate contains a stereogenic center, the compounds of formula (I) can be obtained in the form of a mixture of diastereomers or enantiomers, which can be separated by methods well known in the art (e.g., chiral HPLC, chiral SFC or chiral crystallization). Racemic compounds can be separated into the corresponding enantiomers, for example, by diastereomeric salt formation followed by crystallization with an optically pure acid, or by specific chromatography using a chiral adsorbent or chiral eluent. Starting materials and intermediates containing stereogenic centers can also be separated to provide diastereomer / enantiomer-enriched starting materials and intermediates. The use of such diastereomer / enantiomer-enriched starting materials and intermediates in the synthesis of the compounds of formula (I) will generally result in the corresponding diastereomer / enantiomer-enriched compounds of formula (I).

[0647] Those skilled in the art will recognize that an "orthogonal protecting group strategy" will be applied in the synthesis of the compounds of formula (I) (if desired), which allows for the cleavage of multiple protecting groups at a time without affecting the other protecting groups in the molecule. The principle of orthogonal protection is well known in the art and has also been reported 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).

[0648] Those skilled in the art will recognize that the reaction sequence can vary depending on the reactivity and nature of the intermediates.

[0649] More specifically, the compounds of formula (I) can be prepared by the methods given below, by the methods given in the examples or by analogous methods. The appropriate reaction conditions for each reaction step are known to those skilled in the art. Similarly, for the reaction conditions affecting the said reactions reported in the relevant literature, see, for example: Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 2nd Edition, Richard C. Larock. John Wiley & Sons, New York, NY. 1999. It is convenient to carry out the reactions in the presence or absence of a solvent. There is no particular limitation on the nature of the solvent used, as long as it has no adverse effect on the reaction or the reagents involved and can dissolve the reagents to at least some extent. The described reactions can occur within a wide temperature range, and the exact reaction temperature is not critical for the present invention. The above reactions can be conveniently carried out within the temperature range from -78 °C to reflux. The time required for the reaction can also vary within a wide range, depending on many factors, especially the reaction temperature and the nature of the reagents. However, generally, it takes from 0.5 hours to several days to obtain the said intermediates and compounds. The order of the reaction steps is not limited to the order shown in the scheme, but rather, depending on the starting materials and their corresponding reactivity, the order of the reaction steps can be freely changed.

[0650] If the starting materials or intermediates are not commercially available or their synthesis has not been reported in the literature, they can be prepared by using existing preparation methods similar to those of closely related analogues or according to the overview in the experimental section.

[0651] The following abbreviations are used in this text:

[0652] Ac = acetyl, ACN = acetonitrile, Bn = benzyl, BINAP = (2,2'-bis(diphenylphosphino)-1,1'-binaphthyl), Boc = tert-butoxycarbonyl, CAS RN = Chemical Abstracts Registry Number, Cbz = benzyloxycarbonyl, CMBP = (cyanomethylene)tributylphosphine, Cs 2 CO 3= 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, DMEDA = 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, H 2 O = Water, H 2 SO 4 = Sulfuric acid, HATU = 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate, HBTU = O-Benzotriazol-N,N,N',N'-tetramethyl-uronium-hexafluoro-phosphate, HCl = Hydrogen chloride, HOBt = 1-Hydroxy-1H-benzotriazole; HPLC = High performance liquid chromatography, iPrMgCl = Isopropylmagnesium chloride, I2 = Iodine, IPA = 2-Propanol, ISP = Ion spray positive (mode), ISN = Ion spray negative (mode), K 2 CO 3 = Potassium carbonate, KHCO 3 = Potassium hydrogen carbonate, KI = Potassium iodide, KOH = Potassium hydroxide, K 3 PO 4 = Tripotassium phosphate, LiAlH 4 or LAH = Lithium aluminum hydride, LiHMDS = Lithium bis(trimethylsilyl)amide, LiOH = Lithium hydroxide, mCPBA = meta-Chloroperoxybenzoic acid, MgSO 4 = Magnesium sulfate, min = Minute, mL = Milliliter, MPLC = Medium pressure liquid chromatography, Ms = Methanesulfonyl, MS = Mass spectrometry, MTBE = Methyl tert-butyl ether, nBuLi = n-Butyllithium, NaBH 3CN = sodium cyanoborohydride, NaH = sodium hydride, NaHMDS = sodium bis(trimethylsilyl)amide, NBS = N-bromosuccinimide, NaHCO 3 = sodium bicarbonate, NaNO 2 = sodium nitrite, NaBH(OAc) 3 = sodium triacetoxyborohydride, NaOH = sodium hydroxide, Na 2 CO 3 = sodium carbonate, Na 2 SO 4 = sodium sulfate, Na 2 S 2 O 3 = sodium thiosulfate, NEt 3 = triethylamine (TEA), NH 4 Cl = ammonium chloride, NMP = N-methyl-2-pyrrolidone, OAc = acetoxy, T3P = propylphosphonic anhydride, PE = petroleum ether, PG = protecting group, Pd-C = palladium on activated carbon, PdCl2(dppf)-CH 2 Cl 2 = 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex, Pd 2 (dba) 3 = tris(dibenzylideneacetone)dipalladium(0), Pd(OAc) 2 = palladium(II) acetate, Pd(OH) 2 = palladium hydroxide, Pd(PPh 3 ) 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 2 = zinc chloride, preparative TLC = preparative thin layer chromatography.

[0653] The compound of formula I of the present invention can be prepared by reacting an activated intermediate of formula 2 with a nucleophilic amine 1 in the presence of a base such as DIPEA in a solvent such as DMF or CH 3 CN by heating. (Scheme 1) Alternatively, the activated intermediate can be formed on other coupling partners (1), which will yield the urea of formula I.

[0654]

[0655] Scheme 1

[0656] The activated intermediate 2 can be generated instantaneously in the reaction mixture or by reacting amine 3 with a coupling agent such as bis(1H-1,2,4-triazol-1-yl)methanone in the presence of a base such as DIPEA in a solvent such as CH 2 Cl 2 to generate (Scheme 2). Alternatively, the same strategy as in Schemes 1 and 2 can be used, but the activated intermediate is first constructed on amine 1 before coupling with amine 3.

[0657]

[0658] Scheme 2

[0659] The structural unit of formula 4 (where L = CH 2 , Y = CH) can be generated by Suzuki reaction (e.g., (Pd(dppf)Cl 2 , K 2 CO 3 , dioxane / H 2 O) (X = Br, I) and subsequent hydrogenation (e.g., Pd / C, H 2 ). The required boronic acid compound intermediate 5 can be generated by reacting a 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). In the case of a B=N-linked heteroaryl, a Chan-Lam type coupling can be used instead of the Suzuki reaction, followed by hydrogenation / deprotection.

[0660]

[0661] Scheme 3

[0662] Alternatively, the structural unit of formula 8 (where L = CH 2 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., TsOH when PG = Boc). (Scheme 4)

[0663]

[0664] Scheme 4

[0665] Alternatively, the structural unit of formula 8 (where L = CH2 And A being Y = N) can be prepared by reductive amination of (hetero)aryl methyl halide (X = Br, I, Cl) 11 with a suitably protected spiro A (10) in the presence of a base such as K 2 CO 3 in a solvent such as ACN, followed by deprotection under standard conditions (e.g., using TsOH when PG = Boc). (Scheme 5)

[0666]

[0667] Scheme 5

[0668] Alternatively, the structural unit of formula 12 can be prepared by a Mitsunobu-type reaction of heterocycle B (13) with a hydroxy structural unit 14 (e.g., using diisopropyl azodicarboxylate and triphenylphosphine, or the Tsunoda reagent (cyanomethylene trimethylphosphorane)), followed by deprotection under standard conditions (e.g., using TsOH when PG = Boc). (Scheme 6) Alternatively, the structural unit of formula 12 can be prepared by converting the hydroxy structural unit 14 to a mesylate (e.g., using MsCl, Et 3 N), followed by an S N 2 reaction with heterocycle B (13) in the presence of a base such as NaH.

[0669]

[0670] Scheme 6

[0671] Alternatively, the structural unit of formula 15 (where B is a C-linked heteroaryl and L = -CH 2 -) can be generated using standard heterocyclic synthesis techniques starting from a suitable carboxylic acid or (16) or ester, nitrile (17) or diketone (18) derivative. The nitrile derivative can be generated from a hydroxy derivative (19) via conversion to a mesylate (e.g., using MsCl, Et 3 N), followed by S N 2 displacement of the mesylate group with cyanide (e.g., using KCN). The diketone derivative can be generated from a commercial ester derivative (20) (Scheme 7). A similar sequence can also be applied where B is a C-linked heteroaryl, L = -CH 2 -, and the spiro unit is N-linked (i.e., Y = N).

[0672]

[0673] Scheme 7

[0674] Alternatively, the structural unit of formula 21 (where L = oxygen, Y = CH, and B is a (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 the Tsunoda reagent, (tributylphosphino)acetonitrile, or PPh 3 / DIAD), followed by deprotection. (Scheme 8)

[0675]

[0676] Scheme 8

[0677] (Hetero)aryl trifluoromethylcyclopropyl structural unit 24 is generally not available and is instead generated from a halide structural unit 25 (X = I, Br) via a Suzuki reaction with 1-(trifluoromethyl)vinylboronic acid to give 26. Cyclopropanation using diphenyl(methyl)sulfonium tetrafluoroborate and LiHMDS gives the desired structural unit 24. (Scheme 9) This sequence can also be carried out between the steps of other synthetic schemes. For example, for an N-linked heteroaryl ring B, these functionalization steps can also be carried out while preparing the structural unit of formula 4, after the Suzuki / hydrogenation sequence but before the final deprotection (see Scheme 3). Alternatively, the (hetero)aryl trifluoromethylcyclopropyl structural unit can be generated from commercial structural units via standard heterocyclic synthetic techniques.

[0678]

[0679] Scheme 9

[0680] The structural unit of formula 3 (where A is an N-linked heterocycle) can be prepared by reacting a nucleophilic heterocycle A (27) with a suitably protected structural unit 28 (X = leaving group such as OMs, I, Br) in the presence of a base such as Cs 2 CO 3 or NaH, followed by deprotection under standard conditions (e.g., when PG = Boc, using TsOH; or when PG = Cbz, using palladium-catalyzed hydrogenation). (Scheme 10) Methanesulfonate structural unit 28 (X = OMs) is commonly used and can be conveniently generated from the hydroxyl analogue by reacting with MsCl in the presence of a mild base such as Et 3 N.

[0681]

[0682] Scheme 10

[0683] The structural unit of formula 3 (wherein A is a C-linked heterocycle) can be prepared by standard heterocyclic techniques. For example, structural unit 29 (wherein the A ring is pyrazole) can be generated from hydrazine and diketone 32 by Knorr-type pyrazole synthesis. The required diketone can be generated by reacting a suitable ketone 30 with an acid derivative 31 (X = leaving group, such as OAc, OMe) in the presence of a base (such as NaH, LDA), followed by deprotection under standard conditions. (Scheme 11)

[0684]

[0685] Scheme 11

[0686] Alternatively, the structural unit of formula 3 (wherein A is C-linked) can be generated via a metal-catalyzed cross-coupling reaction using appropriately functionalized intermediates 33 and 34 (X = reactive group), where one partner carries an organometallic (such as zincate, boronic acid compound) typically generated from a halide intermediate (such as I or Br) and the other partner carries a halide (such as Br or I), followed by deprotection under standard conditions. (Scheme 12)

[0687]

[0688] Scheme 12

[0689] In some cases, the compound of formula I can also be generated by combining the described steps into a new combination, for example, coupling according to Scheme 1 before carefully making individual structural units using the same reaction sequence as described above. In some cases, additional protection and deprotection steps are used before, after, or simultaneously with the existing synthetic steps.

[0690] In some cases, the compound of formula I can be further functionalized to obtain other compounds of formula I. For example, a compound of formula I carrying a (hetero)aryl bromide or iodide can be further functionalized with other groups (such as small amines, small alkyl groups) using metal-catalyzed cross-coupling conditions (such as Buchwald or Suzuki reactions). The structural unit 1 can also be further functionalized before or after deprotection of the nucleophilic amine (for example, forming an amide under standard conditions, alkylation of an alcohol (such as using DMF containing NaH and an alkylating agent), converting a boron-containing group to a hydroxyl group using basic peroxide conditions, oxidizing a thioether to a sulfone, or installing a small alkyl group instead of a Br or I group using metal-catalyzed cross-coupling conditions such as Buchwald or Suzuki reactions) to obtain other structural units of formula 1.

[0691] In some cases, the structural units can be generated from commercially available fragments using standard functional group interconversion techniques (e.g., installation of halides (e.g., using NIS or NBS); removal of halides (e.g., under hydrogenation conditions); conversion of halides to other groups (e.g., small molecule amines, small alkyl groups) using metal-catalyzed cross-coupling conditions such as Buchwald or Suzuki reactions; 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 molecule amines; conversion of boron-containing groups to hydroxyl groups using basic peroxide conditions; cycloaddition of azidotrimethylsilane with nitriles to form tetrazoles; obtaining bromides through the Sandmeyer reaction of anilines; oxidation of thioethers to sulfones; using PhI(OAc) 2 and NH 2 COONH 4 oxidation of thioethers to sulfoximines; alkylation of hydroxyl or amino groups via S N 2 reactions or reductive amination; acylation using activated carbonyl derivatives; installation of –SO 2 Me or –SO 2 CF 3 ; under Chan-Lam type conditions, installation of small alkyl groups or rings (such as cyclopropyl) onto heteroaromatic nitrogens using boric acid compound derivatives; 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 Et 3 N. Such techniques can also be used to elaborate commercially available fragments before, after, or in the middle of the above synthetic sequence reactions. In some cases, the structural units can be generated from commercially available fragments using standard heterocyclic synthesis techniques (e.g., synthesis of pyrazoles, oxadiazoles, imidazoles).

[0692] In one aspect, the present invention provides a method for manufacturing a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein the method is as described in any one of Schemes 1 to 12.

[0693] In one aspect, the present invention provides a method for manufacturing a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, the method comprising reacting a compound of formula 2;

[0694]

[0695] wherein A and R 3 are as defined herein, with a compound of formula 1,

[0696]

[0697] wherein R 1 and R 2 , B, L, W, Y and Z are as defined herein; the reaction is carried out by heating in a solvent such as DMF or CH 3 CN in the presence of a base such as DIPEA to form the compound of formula (I).

[0698] In one aspect, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof, which is prepared according to any of the methods described herein.

[0699] MAGL inhibitory activity

[0700] The compounds of the present invention are MAGL inhibitors. Thus, in one aspect, the present invention provides the use of a compound of formula (I) as described herein for inhibiting MAGL in a mammal.

[0701] In another aspect, the present invention provides a compound of formula (I) as described herein for use in a method of inhibiting MAGL in a mammal.

[0702] In another 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.

[0703] In another aspect, the present invention provides a method for inhibiting MAGL in a mammal, which method comprises administering to the mammal an effective amount of a compound of formula (I) as described herein.

[0704] The inhibitory activity of the compounds of formula (I) against MAGL was analyzed by measuring the enzymatic activity after hydrolysis of the natural substrate 2-arachidonoylglycerol (2-AG) to arachidonic acid, followed by mass spectrometry analysis. This assay is abbreviated as "2-AG assay" hereinafter. The 2-AG assay was performed in 384-well polypropylene assay plates. In the polypropylene plates, compound dilutions were prepared in 100% DMSO using a 3-fold dilution step to give a final concentration range for the assay of 12.5 μM to 0.8 pM. The compound dilutions were added to the assay buffer (50 mM TRIS, 1 mM EDTA, 0.01% (v / v) Tween-20, 2.5% (v / v) DMSO) containing MAGL protein. After shaking, the plates were incubated at RT for 15 min. The assay buffer solution of 2-arachidonoylglycerol was added to initiate the reaction. The final concentrations in this assay were 50 pM MAGL protein and 8 μM 2-arachidonoylglycerol. After shaking and incubating at RT for 30 min, the reaction was quenched by adding twice the assay volume of acetonitrile containing 4 μM d8-arachidonic acid. The amount of arachidonic acid formed was traced using an online SPE system (Agilent Rapidfire) coupled with a triple quadrupole mass spectrometer system. In the acetonitrile / water liquid position, a C18 SPE column (Agilent G9205A) was used. The mass spectrometer was operated in the negative electrospray mode, and the mass ion pairs for arachidonic acid were 303.1→259.1, and for d8-arachidonic acid were 311.1→267.0. The activity of the compound was calculated based on the intensity ratio of [arachidonic acid / d8-arachidonic acid].

[0705] Table 1

[0706]

[0707]

[0708]

[0709]

[0710]

[0711]

[0712] Using the compounds of the present invention

[0713] 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 therapeutic active substance.

[0714] In another aspect, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein for use in a method of inhibiting monoacylglycerol lipase in a mammal.

[0715] In another aspect, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein for use in the treatment or prevention of diseases and disorders associated with monoacylglycerol lipase in a mammal.

[0716] In another 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) or a pharmaceutically acceptable salt thereof as described herein.

[0717] In another aspect, the present invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein in the preparation of a medicament for the treatment or prevention of diseases or disorders associated with monoacylglycerol lipase in a mammal.

[0718] In another aspect, the present invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein for the treatment or prevention of diseases or disorders associated with monoacylglycerol lipase in a mammal.

[0719] In one embodiment, the disease or disorder associated with monoacylglycerol lipase is selected from neuroinflammation, neurodegenerative diseases, pain, cancer, mental disorders, and / or inflammatory bowel disease.

[0720] In one embodiment, the disease or disorder 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 disorder, migraine, depression, hepatocellular carcinoma, colon carcinogenesis, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, pain-related spasm, abdominal pain, abdominal pain associated with irritable bowel syndrome, visceral pain, and inflammatory bowel disease.

[0721] In one embodiment, the disease or disorder associated with monoacylglycerol lipase is selected from neuroinflammation, neurodegenerative diseases, pain, cancer, mental disorders, and inflammatory bowel disease in a mammal.

[0722] 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.

[0723] In one embodiment, the disease or disorder associated with monoacylglycerol lipase is multiple sclerosis.

[0724] In one embodiment, the disease or disorder associated with monoacylglycerol lipase is selected from neuroinflammation and neurodegenerative diseases.

[0725] In one embodiment, the disease or disorder associated with monoacylglycerol lipase is a neurodegenerative disease.

[0726] In one embodiment, the disease or disorder associated with monoacylglycerol lipase is cancer.

[0727] In one embodiment, the disease or disorder associated with monoacylglycerol lipase is inflammatory bowel disease.

[0728] In one embodiment, the disease or disorder associated with monoacylglycerol lipase is pain.

[0729] Pharmaceutical compositions and administration

[0730] In one aspect, the present invention provides a pharmaceutical composition comprising a compound of formula (I) as described herein and a therapeutically inert carrier.

[0731] In one embodiment, there is provided a pharmaceutical composition according to Example 310 or 311.

[0732] The compound of formula (I) and its pharmaceutically acceptable salts can be used as a medicine (for example, in the form of a pharmaceutical preparation). The pharmaceutical preparation can be administered internally, such as orally (for example, in the form of tablets, coated tablets, lozenges, hard gelatin capsules and soft gelatin capsules, solutions, emulsions or suspensions), intranasally (for example, in the form of a nasal spray) or rectally (for example, in the form of a suppository). However, it can also be administered parenterally, such as intramuscularly or intravenously (for example, in the form of an injection solution).

[0733] The compound of formula (I) and its pharmaceutically acceptable salts can be processed together with pharmaceutically inert inorganic or organic adjuvants to produce tablets, coated tablets, lozenges and hard gelatin capsules. For example, lactose, corn starch or its derivatives (such as talc, stearic acid or its salts, etc.) can be used as such adjuvants for tablets, dragees and hard gelatin capsules.

[0734] Suitable adjuvants for soft gelatin capsules are, for example, vegetable oils, waxes, fats, semi-solid substances and liquid polyols, etc.

[0735] Suitable adjuvants for preparing solutions and syrups are, for example, water, polyols, sucrose, invert sugar, glucose, etc.

[0736] Suitable adjuvants for injection solutions are, for example, water, alcohols, polyols, glycerol, vegetable oils, etc.

[0737] Suitable auxiliaries for suppositories are, for example, natural or hardened oils, waxes, fats, semi-solid or liquid polyols, etc.

[0738] In addition, the pharmaceutical preparation may contain preservatives, solubilizers, thickening substances, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, fragrances, salts for changing the osmotic pressure, buffer masking agents or antioxidants. They may also contain other substances of therapeutic value.

[0739] The dosage can vary within a wide range and will of course be suitable for the various requirements in each specific case. Generally, a daily dosage for oral administration of about 0.1 mg to 20 mg per kg body weight, preferably about 0.5 mg to 4 mg per kg body weight (e.g., about 300 mg per person) should be suitable, which is preferably divided into 1 - 3 individual doses (which may consist of, for example, the same amount). However, it is obvious that when indicated as such, the upper limit given herein may be exceeded.

[0740] Examples

[0741] The present invention will be more fully understood by reference to the following examples. However, the claims should not be construed as being limited to the scope of the examples.

[0742] In the case where the preparation examples are obtained as mixtures of enantiomers, the pure enantiomers can be separated by the methods described herein or by methods known to those skilled in the art (such as chiral chromatography (e.g., chiral SFC) or crystallization).

[0743] Unless otherwise stated, all reaction examples and intermediates are prepared under an argon atmosphere.

[0744] Example 1

[0745] [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

[0746]

[0747] 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) was added DIPEA (108 mg, 146 μL, 0.838 mmol), followed by bis(1,2,4-triazol-1-yl)methanone (19.6 mg, 0.120 mmol), and then 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, and then it was stirred at 50 °C for 18 h. The crude reaction mixture was directly purified by reverse-phase HPLC to give the title compound as a colorless gum (38.9 mg). MS (ESI): m / z = 506.3 [M+H] +

[0748] Similar to Example 1, the examples in the following table were generated by urea coupling using the corresponding structural units A.X and B.X.

[0749]

[0750]

[0751]

[0752]

[0753]

[0754]

[0755]

[0756]

[0757]

[0758]

[0759]

[0760]

[0761]

[0762]

[0763]

[0764]

[0765]

[0766]

[0767]

[0768]

[0769]

[0770]

[0771]

[0772]

[0773]

[0774]

[0775]

[0776]

[0777]

[0778]

[0779]

[0780]

[0781]

[0782]

[0783]

[0784]

[0785]

[0786]

[0787]

[0788]

[0789]

[0790]

[0791]

[0792]

[0793]

[0794]

[0795]

[0796]

[0797]

[0798]

[0799]

[0800]

[0801]

[0802]

[0803]

[0804]

[0805]

[0806]

[0807]

[0808]

[0809]

[0810]

[0811]

[0812]

[0813]

[0814]

[0815]

[0816]

[0817]

[0818]

[0819]

[0820]

[0821] Example 330

[0822] [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

[0823]

[0824] To a solution of tert-butyl N-[1-[1-(2-azaspiro[3.3]heptan-6-yl)-1,2,4-triazol-3-yl]cyclopropyl]carbamate; acetic acid (A.7) (145 mg, 306 μmol) in N,N-dimethylformamide (1.78 mL) 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), and then 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, and then the reaction mixture was stirred at 50 °C for 18 h. 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), and then the reaction mixture was stirred at RT for 18 h. Volatiles were removed in vacuo, the crude residue was dissolved in DMF, and the crude solution was purified directly by reverse-phase HPLC to afford the title compound as a colorless gum (6.7 mg). MS (ESI): m / z = 505.4 [M+H] +

[0825] Step a) tert-Butyl N-[1-(1H-1,2,4-triazol-3-yl)cyclopropyl]carbamate

[0826] A solution of tert-butyl N-(1-carbamoylcyclopropyl)carbamate (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. The volatiles were removed in vacuo and the resulting crude residue was dissolved in 1,4-dioxane (80 mL), followed by the addition of 35% aqueous hydrazine (5.19 g, 5.08 mL, 56.7 mmol) and acetic acid (3.4 g, 3.24 mL, 56.7 mmol), and then the reaction mixture was stirred at 70 °C for 4 h. The reaction mixture was poured into a separatory funnel containing EtOAc and saturated NH 4 Cl aqueous solution. 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), which was a light pink solid and was used without further purification. MS (ESI): m / z = 169.0 [M - C 4 H 8 + H] +

[0827] Step b) Benzyl 6-[3-[1-(tert-butoxycarbonylamino)cyclopropyl]-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carboxylate

[0828] To a solution of benzyl 6-methylsulfonyloxy-2-azaspiro[3.3]heptane-2-carboxylate (CAS: 2966056-53-9) (7.69 g, 23.6 mmol) in N,N-dimethylformamide (102 mL) was added tert-butyl N-[1-(1H-1,2,4-triazol-3-yl)cyclopropyl]carbamate (5.05 g, 22.5 mmol) and cesium carbonate (11.0 g, 33.8 mmol), and then 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 phase 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 a crude residue, which was purified by flash chromatography (eluent: heptane / ethyl acetate 5% to 75%) to give the title compound (4.22 g), which was a white solid. MS (ESI): m / z = 454.3 [M + H] +

[0829] Note: The title compound was formed together with a positional isomeric by-product. The identification result was confirmed by NMR analysis.

[0830] Step c) tert-Butyl N-[1-[1-(2-azaspiro[3.3]heptan-6-yl)-1,2,4-triazol-3-yl]cyclopropyl]carbamate; acetic acid (A.7)

[0831] A solution of benzyl 6-[3-[1-(tert-butoxycarbonylamino)cyclopropyl]-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carboxylate (4160 mg, 9.17 mmol) in methanol (30 mL) and AcOH (1.57 mL) in a pressure vessel was placed under argon. A catalyst, 20% Pd(OH) 2 / C (wet) (416 mg), was added, the vessel was evacuated and filled with hydrogen. The reaction was stirred at H 2 (3 bar) at 40 °C for 18 h, cooled and filtered. The vessel and the 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 (purity approximately 80%). MS (ESI) m / z = 320.3 [M+H] +

[0832] Synthesis of structural units

[0833] Example A.1

[0834] 6-(3-Cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane; 4-methylbenzenesulfonic acid

[0835]

[0836] At 23 °C, 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). 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 Et 2 O and left at 0 °C for 16 h. The resulting solid was filtered off and dried to give the desired product (6.0 g, 86% yield), which was a white solid. MS (ESI): m / z = 205.2 [M+H-Tos] +

[0837] Step a): tert-Butyl 6-hydroxy-2-azaspiro[3.3]heptane-2-carboxylate

[0838] In N 2Under 0 °C, NaBH 4 (7.16 g, 189.34 mmol) was added 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). The mixture was stirred at 0 °C for 1 h and then evaporated. The residue was dissolved in saturated NaHCO 3 aqueous solution, and the aqueous solution was extracted with DCM. The combined organic layers were dried over MgSO 4 , filtered and evaporated to give the title compound (19 g, yield 94%), which is a white solid. MS (ESI): m / z = 158.1 [M+H] +

[0839] Step b): tert-butyl 6-methylsulfonyloxy-2-azaspiro[3.3]heptane-2-carboxylate

[0840] Two batches were carried out in parallel. TEA (128.0 g, 1172.2 mmol) was added to a solution of tert-butyl 6-hydroxy-2-azaspiro[3.3]heptane-2-carboxylate (100 g, 468.9 mmol) in DCM (1000 mL) at 23 °C. Then the reaction mixture was 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, then the two batches were combined and poured into water (2 L). The organic layer was separated, washed with brine (2 x 2000 mL), dried over Na 2 SO 4 , filtered and evaporated to give the crude title compound (269 g, quantitative), which is a white solid and was used directly in the next step.

[0841] Step c): tert-butyl 6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate

[0842] Cesium carbonate (559.14 g, 1716.09 mmol) was added to a mixture of 3-cyclopropyl-1H-1,2,4-triazole (112.37 g, 1029.65 mmol) and tert-butyl 6-methylsulfonyloxy-2-azaspiro[3.3]heptane-2-carboxylate (250.0 g, 858.05 mmol) in ACN (2500 mL). The mixture was stirred at 70 °C for 16 h, then filtered and evaporated. Purification by FC (SiO 2 ; DCM / THF / PE) gave the desired compound (1.10 g, yield 40.0%), which is a yellow solid. MS (ESI): m / z = 305.3 [M+H]+

[0843] Example A.2

[0844] 1-[1-(2-Azaspiro[3.3]heptan-6-yl)-1,2,4-triazol-3-yl]cyclopropanol; 2,2,2-trifluoroacetic acid

[0845]

[0846] To a solution of tert-butyl 6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carboxylate (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] +

[0847] Step a): 3-(1-benzoyloxycyclopropyl)-1H-1,2,4-triazole

[0848] A solution of 1-benzoyloxycyclopropanecarboxamide (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 NH 4 Cl. After extraction, the organic phase was collected, and the aqueous phase was back-extracted with 150 mL of ethyl acetate. The combined organic phases were dried over sodium sulfate and evaporated to give the crude desired product (10.45 g, 97% yield). MS (ESI): m / z = 216.2 [M+H] +

[0849] Step b): tert-butyl 6-hydroxy-2-azaspiro[3.3]heptane-2-carboxylate

[0850] At N 2 under 0 °C, 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 4(7.16 g, 189.34 mmol). The mixture was stirred at 0 °C for 1 h and then evaporated. The residue was dissolved in saturated NaHCO 3 aqueous solution, and the aqueous solution was extracted with DCM. The combined organic layers were dried over MgSO 4 and filtered and evaporated to give the title compound (19 g, 94% yield), which was a white solid. MS (ESI): m / z = 158.1 [M+H] +

[0851] Step c): tert-Butyl 6-methylsulfonyloxy-2-azaspiro[3.3]heptane-2-carboxylate

[0852] Two batches were carried out 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) at 23 °C was added TEA (128.0 g, 1172.2 mmol). 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, then the two batches were combined and poured into water (2 L). The organic layer was separated, washed with brine (2 x 2000 mL), dried over Na 2 SO 4 and filtered and evaporated to give the crude title compound (269 g, quantitative), which was a white solid and was used directly in the next step.

[0853] Step d): tert-Butyl 6-[3-(1-benzyloxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carboxylate

[0854] Under nitrogen, to a solution of 3-(1-benzyloxycyclopropyl)-1H-1,2,4-triazole (22.0 g, 102.21 mmol) in NMP (220 mL) at 0 °C was added NaH (4.42 g, 183.97 mmol). 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 NH 4 Cl aqueous solution, and extracted with EtOAc. The combined organic layers were washed with 400 mL of brine, dried over Na 2 SO 4 and filtered and evaporated. By FC (SiO 2;Purified by PE / EtOAc) to obtain the desired product (22.22 g, yield 51.95%), which is a yellow solid. MS (ESI): m / z = 411.1 [M+H] +

[0855] Step e): tert-Butyl 6-[3-(1-hydroxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carboxylate

[0856] A solution of tert-butyl 6-[3-(1-benzoyloxycyclopropyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carboxylate (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 a H2 atmosphere and stirred at 50 °C and 2 bar for 5 h, then returned to an Ar atmosphere, filtered, and evaporated. Purified by FC (SiO2; heptane / EtOAc / EtOH) to obtain the desired product (26.25 g, yield 85%), which is a white solid. MS (ESI): m / z = 321.3 [M+H] +

[0857] Example A.3

[0858] 6-[3-(Trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane; 4-methylbenzenesulfonic acid

[0859]

[0860] 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 obtain the desired compound (40.0 g, yield 95.43%), which is a yellow solid. MS (ESI): m / z = 233.1 [M - TsOH + H] +

[0861] Step a): tert-Butyl 6-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carboxylate

[0862] Under Ar, 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 cyanide (2.21 g, 55.18 mmol) in oil. The mixture was stirred at 20 °C for 1 h, and a solution of 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 2 SO 4 dried and evaporated. Purification by FC (SiO 2 ; PE / EtOAc) gave the desired compound (10.7 g, yield 70.02%), which was a white solid. MS (ESI): m / z = 277.2 [M - Bu + H] +

[0863] Example A.4

[0864] 6-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptane; 2,2,2-trifluoroacetic acid

[0865]

[0866] To a solution of tert-butyl 6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptane-2-carboxylate (1.80 g, 5.93 mmol) in dichloromethane (21 mL) at 23 °C was added TFA (4.57 mL, 59.33 mmol). The mixture was stirred at this temperature for 18 h, then evaporated to give the desired compound (3.69 g, quantitative), which was a pale yellow viscous oil. MS (ESI): m / z = 204.2 [M + H] + Step a): tert-Butyl 6-(3-cyclopropyl-3-oxopropanoyl)-2-azaspiro[3.3]heptane-2-carboxylate

[0867] 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) at 20 °C was added methyl cyclopropyl ketone (2.96 g, 35.25 mmol) and NaH (2.37 g, 98.7 mmol). 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 Na 2 SO4 Dry, filter and evaporate. Purify by FC (PE / EtOAc) to give the desired product (4.9 g, yield 45.2%), which is a yellow solid.

[0868] Step b): tert-Butyl 6-(3-cyclopropyl-1H-pyrazol-5-yl)-2-azaspiro[3.3]heptane-2-carboxylate

[0869] A mixture of tert-butyl 6-(3-cyclopropyl-3-oxopropanoyl)-2-azaspiro[3.3]heptane-2-carboxylate (1.0 g, 3.25 mmol) and 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 and dried over Na 2 SO 4 Dry, filter and evaporate. Purify by FC (SiO 2 , PE / EtOAc) to give the desired product (930.0 mg, yield 94.22%), which is a yellow solid. MS (ESI): m / z = 248.1 [M+H] +

[0870] Example A.5

[0871] 1-[5-(2-Azaspiro[3.3]heptan-6-yl)-1H-pyrazol-3-yl]cyclopropanol; 2,2,2-trifluoroacetic acid

[0872]

[0873] To a solution of tert-butyl 6-[3-(1-hydroxycyclopropyl)-1H-pyrazol-5-yl]-2-azaspiro[3.3]heptane-2-carboxylate (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 crude desired product (794 mg, quantitative), which is a pale yellow viscous oil. MS (ESI): m / z = 220.2 [M+H] +

[0874] Step a): 1-[(tert-Butyl(diphenyl)silyl)oxy]-N-methoxy-N-methyl-cyclopropanecarboxamide

[0875] At 25 °C, HATU (3.62 g, 9.52 mmol) and DIPEA (3586.94 mg, 27.75 mmol) were added 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). 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 H 2 O (50 mL) and extracted with EtOAc. The combined organic layers were washed with saturated aqueous NaCl solution, dried over anhydrous Na 2 SO 4 , filtered and evaporated. Purification by FC (SiO 2 , PE / EtOAc) gave the desired compound (2.8 g, yield 92.06%), which was a yellow solid.

[0876] Step b): 1-[1-[tert-butyl(diphenyl)silyl]oxycyclopropyl]ethanone

[0877] At 0 °C, methylmagnesium bromide (0.6605 mL, 3 M in diethyl ether) was added 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), and the reaction mixture was stirred at 20 °C for 2 h. The reaction mixture was quenched by adding saturated NH 4 Cl aqueous solution (50 mL) at 25 °C, then diluted with H 2 O (50 mL) and extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na 2 SO 4 , filtered and evaporated to give the desired compound (2.0 g, yield 80.93%), which was a yellow oil.

[0878] Step c): 1-[1-[tert-butyl(diphenyl)silyl]oxycyclopropyl]ethanone

[0879] At 0 °C, 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 isobutyl chloroformate (1.87 g, 13.68 mmol). 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 Na 2 SO4 Dry, filter, and evaporate to obtain the desired compound (4.2 g, yield 98.94%), which is a yellow oil.

[0880] Step d): tert-Butyl 6-[3-[1-[tert-butyl(diphenyl)silyl]oxycyclopropyl]-3-oxopropanoyl]-2-azaspiro[3.3]heptane-2-carboxylate

[0881] Under Ar, at -78 °C, LDA (5.91 mL, 11.82 mmol) (2 M in THF) was added to a solution of 1-[1-[tert-butyl(diphenyl)silyl]oxycyclopropyl]ethanone (2000.0 mg, 5.91 mmol) in THF (40 mL). The mixture was stirred at this temperature for 1 h, 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 another hour 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 solution, dried over Na 2 SO 4 Dry, filter, and evaporate. Purify by FC (SiO 2 , PE / EtOAc) to obtain the desired compound (2.0 g, yield 60.3%), which is a yellow solid. MS (ESI): m / z = 484.3 [M+H] +

[0882] Step e): tert-Butyl 6-[3-(1-hydroxycyclopropyl)-1H-pyrazol-5-yl]-2-azaspiro[3.3]heptane-2-carboxylate

[0883] At 20 °C, hydrazine (228.17 mg, 7.12 mmol) was added to a solution of tert-butyl 6-[3-[1-[tert-butyl(diphenyl)silyl]oxycyclopropyl]-3-oxopropanoyl]-2-azaspiro[3.3]heptane-2-carboxylate (2.0 g, 3.56 mmol) in ethanol (20 mL). The mixture was stirred at 50 °C for 1 h, then cooled and purified by RP-HPLC to obtain the desired compound (383.0 mg, yield 33.51%), which is a white solid. MS (ESI): m / z = 320.2 [M+H] +

[0884] Example A.6

[0885] 6-[3-(Difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane; 2,2,2-trifluoroacetic acid

[0886]

[0887] To a solution of tert-butyl 6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carboxylate (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 RT for 18 h. Volatiles were removed in vacuo to afford 3340 mg of the crude title compound (purity ~50%, major contaminant excess TFA) as a colorless viscous oil, which was used without further purification. MS (ESI): m / z = 215.2 [M+H] +

[0888] Step a) tert-butyl 6-[3-(difluoromethyl)-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptane-2-carboxylate

[0889] To a solution of tert-butyl 6-methylsulfonyloxy-2-azaspiro[3.3]heptane-2-carboxylate (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 then the reaction mixture was stirred at 90 °C for 18 h. Volatiles were removed in vacuo, and the crude residue was partitioned between ethyl acetate and 1 M Na 2 CO 3 aqueous solution, 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 afford a residue, which was purified by flash chromatography (eluent: a mixture of heptane and ethyl acetate (10% to 80%)) to afford the title compound as a white solid. MS (ESI): m / z = 315.2 [M+H] +

[0890] Note: A small amount of alternative regioisomer was also isolated. The regioselectivity of the chemistry was confirmed by NMR analysis.

[0891] Example B.34

[0892] 5-(2-azaspiro[3.3]heptan-6-ylmethyl)-3-(trifluoromethyl)-1,2,4-thiadiazole; 4-methylbenzenesulfonic acid

[0893]

[0894] 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, yield 71.2%), which was a light yellow solid. MS (ESI): m / z = 264.0 [M - TsOH + H] +

[0895] Step a) tert-Butyl 6-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]-2-azaspiro[3.3]heptane-2-carboxylate

[0896] 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 2 atmosphere. n-BuLi (227 mL, 568 mmol) was added dropwise, and the reaction mixture was stirred at the same temperature for 30 min. Next, the reaction 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 min, 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. H 2 O (80 mL) was slowly added to the mixture, and then it was purified together with another batch of the same size by a silica gel column (PE / EA = 1:0 to 3:1 gradient) to give the title compound (220 g, 656 mmol, yield of each batch was approximately 69%), which was a white solid and was confirmed by the following: 1 1H 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).

[0897] Step b) tert-Butyl 6-[[3-(trifluoromethyl)-1,2,4-thiadiazol-5-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate

[0898] 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-dichloropalladium(II) 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 h. 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 thin-layer silica gel, and evaporated. The crude product was purified by flash chromatography (hexane / ethyl acetate 0% to 35%) to afford 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), which was a gray solid. MS (ESI): m / z = 360.0 [M-H] - 。

[0899] Step c) tert-Butyl 6-[[3-(trifluoromethyl)-1,2,4-thiadiazol-5-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[0900] 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 10% Pd / C (574 mg, 0.54 mmol) in EtOAc (120 mL) was stirred in a reaction vessel at H 2 under 30 bar for 24 h. The reaction mixture was then filtered and concentrated to afford the title compound (6.51 g, 17.9 mmol, 99.6% yield), which was a colorless oil. MS (ESI): m / z = 362.2 [M-H] - 。

[0901] Similar to Example B.34, the following structural units are generated in step b using (hetero)aryl bromide or iodide structural units for Suzuki coupling. In some cases, alternative salts (e.g., trifluoroacetate, xylenesulfonate, hydrochloride) are also used. To introduce different spiro ring systems, additional structural unit substitutions can be made. For example, in Example B.353, tert-butyl 7-oxo-2-azaspiro[3.5]nonane-2-carboxylate (CAS: 1363381-22-9) is used in step a) instead of tert-butyl 6-oxo-2-azaspiro[3.3]heptane-2-carboxylate. In some cases, the synthesis is planned to include removal of an additional Br group in the hydrogenation step.

[0902]

[0903]

[0904]

[0905]

[0906]

[0907]

[0908]

[0909]

[0910] Example B.32

[0911] 6-[[4-(Trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane; 4-methylbenzenesulfonic acid

[0912]

[0913] 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 h. 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, yield 96%), which was a white solid. MS (ESI): m / z = 246.2 [M - TsOH + H] + Step a) tert-butyl 6-[[4-(trifluoromethyl)pyrazol-1-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate

[0914] Under an O 2 atmosphere, copper(II) diacetate (2380 mg, 11.9 mmol) was added 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), and then the mixture was stirred at 100 °C for 12 h under an O 2 (balloon) atmosphere. The aqueous phase was extracted with ethyl acetate (200 mL × 3). The combined organic phases were washed with brine (200 mL × 3), dried over anhydrous Na 2 SO 4 , filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography (eluent: 0% to 30% ethyl acetate / petroleum ether) to give a crude product, which was purified by reverse-phase HPLC (0.1% FA conditions) to give the title compound (640 mg, yield 31%), which was a brown solid. MS (ESI): m / z = 288.1 [M-tBu+H] +

[0915] Step b) tert-butyl 6-[[4-(trifluoromethyl)pyridazin-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[0916] 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 EtOAc (7 mL) was added wet Pd / C (230 mg, 0.200 mmol), and the mixture was stirred at 25 °C for 2 h under an H 2 atmosphere (balloon). The mixture was then filtered and the filtrate was concentrated to give the title compound (690 mg, yield 99%), which was a yellow solid. MS (ESI): m / z = 346.1 [M+H] +

[0917] Similar to Example B.32, the following structural units were generated in Step 1 using the relevant (hetero)aryl structural units for Chan Lam coupling. In some cases, alternative salts (e.g., trifluoroacetate, xylenesulfonate, hydrochloride) were also used.

[0918]

[0919]

[0920] Example B.347

[0921] 5-(2,6-Diazaspiro[3.3]heptan-2-ylmethyl)-2-(trifluoromethyl)thiazole; 4-Methylbenzenesulfonic acid

[0922]

[0923] 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) was added p-toluenesulfonic acid monohydrate (3141 mg, 16.5 mmol, 3.0 eq), and the mixture was 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), which was a white solid. MS (ESI): m / z = 264.0 [M–TsOH+H] +

[0924] Step a) tert-Butyl 6-[[2-(trifluoromethyl)thiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptane-2-carboxylate

[0925] 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 (chloroform containing 0% to 80% acetonitrile) to give the title compound (2000 mg, 5.5 mmol, 66.5% yield), which was a light brown solid. MS (ESI): m / z = 364.0 [M+H] + .

[0926] Similar to Example B.347, the following structural units were generated in step a) using the relevant structural units.

[0927]

[0928]

[0929]

[0930]

[0931]

[0932]

[0933]

[0934]

[0935]

[0936]

[0937]

[0938]

[0939]

[0940]

[0941]

[0942]

[0943]

[0944]

[0945]

[0946]

[0947]

[0948] Example B.360

[0949] 3-Cyclopropyl-5-(2,6-diazaspiro[3.3]heptan-2-ylmethyl)-1,2,4-thiadiazole; 4-methylbenzenesulfonic acid

[0950]

[0951] 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] +

[0952] Step a) tert-butyl 6-[(3-cyclopropyl-1,2,4-thiadiazol-5-yl)methyl]-2,6-diazaspiro[3.3]heptane-2-carboxylate

[0953] 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 h and evaporated. The residue was purified by HPLC to give the title compound (558 mg, 1.66 mmol, 53.4% yield), which was a light yellow solid. MS (ESI): m / z = 337.0 [M+H]+

[0954] Similar to Example B.360, the following structural units were generated using the relevant commercial structural units in step b). For 4,6- or 4,5-spirocyclic systems, tert-butyl 2,7-diazaspiro[3.5]nonane-2-carboxylate and tert-butyl 2,6-diazaspiro[3.4]octane-2-carboxylate can be used instead of tert-butyl 2,6-diazaspiro[3.3]heptane-2-carboxylate, respectively. In some cases, Cs 2 CO 3 is used instead of K 2 CO 3 . In some cases, alternative salts (e.g., hydrochloride) of the commercial spirocyclic amine structural units are used.

[0955]

[0956]

[0957]

[0958]

[0959]

[0960] Example B.311

[0961] 6-[[5-(Trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane; 4-methylbenzenesulfonic acid

[0962]

[0963] 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 EtOAc (2 mL) was added p-toluenesulfonic acid (110 mg, 0.64 mmol), and the mixture was stirred at 80 °C for 12 h. The reaction mixture was filtered and concentrated under reduced pressure to afford the title compound (230 mg, 0.55 mmol, 95% yield), which was a yellow oil. MS (ESI): m / z = 246.1 [M+H] + .

[0964] Step a) tert-butyl 6-[[5-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[0965] To a mixture of tert-butyl 6-(hydroxymethyl)-2-azaspiro[3.3]heptane-2-carboxylate (CAS: 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) at 0 °C was added diisopropyl azodicarboxylate (10.4 mL, 52.8 mmol), and then the reaction mixture was stirred at 20 °C for 12 h under N 2 2. The reaction mixture was diluted with 100 mL of water and extracted with 300 mL (100 mL x 3) of EtOAc. The combined organic layers were washed with saturated NaCl solution (50 mL) and dried over Na 2 SO 4 4, filtered, and concentrated under reduced pressure to give a residue. The residue was purified by normal-phase preparative HPLC to afford the title compound (3.7 g, 10.7 mmol, 24.4% yield), which was a yellow solid. MS (ESI): m / z = 346.1 [M+H] +

[0966] Similar to Example B.311, the following structural units were generated using the relevant commercial structural units in step a).

[0967]

[0968] Example B.317

[0969] 2-(2-Azaspiro[3.3]heptan-6-ylmethyl)-5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazole; 4-methylbenzenesulfonic acid

[0970]

[0971] To a solution of tert-butyl 6-[[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (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. Et 2 O (100 mL) was added (partial crystallization began overnight). The mixture was concentrated in vacuo to afford the title compound (4.25 g, 45%) as a white solid. MS (ESI): m / z = 288.0 [M+H] +

[0972] Step a) tert-butyl 6-(2-hydrazinyl-2-oxo-ethyl)-2-azaspiro[3.3]heptane-2-carboxylate

[0973] 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, hydrazine monohydrate (1.47 g, 1.42 mL, 29.4 mmol) was added, and the mixture was stirred at RT for 30 min. The reaction mixture was poured into EtOAc / THF 2:1, washed with water and brine, dried over Na 2 SO 4 and concentrated in vacuo to afford the title compound (3.85 g, 99%) as a white solid. MS (ESI): m / z = 214.1 [M+H-C 4 H 8 +

[0974] Step b) tert-butyl 6-[2-oxo-2-[N'-[1-(trifluoromethyl)cyclopropanecarbonyl]hydrazinyl]ethyl]-2-azaspiro[3.3]heptane-2-carboxylate

[0975] ​To a solution of 1-(trifluoromethyl)cyclopropanecarboxylic acid (CAS: 277756-46-4) (1.5 g, 9.72 mmol) in dichloromethane (30 mL) was added 1-chloro-N,N,2-trimethylallylamine (1.56 g, 1.54 mL, 11.7 mmol). The mixture was stirred at RT for 2 h. The acyl chloride solution was added dropwise at room temperature to a solution of tert-butyl 6-(2-hydrazinyl-2-oxo-ethyl)-2-azaspiro[3.3]heptane-2-carboxylate (3.85 g, 9.72 mmol) and DIEA (2.51 g, 3.4 mL, 19.4 mmol) in tetrahydrofuran (20 mL). The reaction mixture was stirred at RT for 2 h. The reaction mixture was poured into EtOAc / THF 2:1 and washed with water and brine. The organic layer was dried over Na 2 SO 4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 80 g, CH 2 Cl 2 containing 0% to 5% methanol) to afford the title compound (3.49 g, 84.14%), which was a white solid. MS (ESI): m / z = 350.1 [M+H - C 4 H 8 + Step c) tert-Butyl 6-[[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[0976] To a solution of tert-butyl 6-[2-oxo-2-[N'-[1-(trifluoromethyl)cyclopropanecarbonyl]hydrazino]ethyl]-2-azaspiro[3.3]heptane-2-carboxylate (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 Na 2 SO 4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 80 g, CH 2 Cl 2 ) to afford tert-butyl 6-[[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (3.22 g, 92%), which was a white solid. MS (ESI): m / z = 388.2 [M+H] + .

[0977] Example P.50 ​

[0978] 1-(2-Azaspiro[3.3]heptan-6-ylmethyl)-4-(trifluoromethyl)pyridin-2-one; 4-Methylbenzenesulfonic acid

[0979]

[0980] To a solution of tert-butyl 6-[[4-(trifluoromethyl)-1,2,3-triazol-2-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (2.5 g, 7.2 mmol) in EtOAc (100 mL) 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 afford the title compound (3.63 g, 81% yield), which was a white powder. MS (ESI): m / z = 247.2 [M+H] + 。

[0981] Step a) tert-Butyl 6-(methylsulfonyloxymethyl)-2-azaspiro[3.3]heptane-2-carboxylate

[0982] 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, then methanesulfonyl chloride (6.1 mL, 78.9 mmol) was added dropwise, and then the reaction mixture was stirred at room temperature for 4 h. The reaction mixture was diluted with water and extracted with DCM, washed with water, brine, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to afford the title compound as a yellow solid (19.8 g, 64.8 mmol, 93.7% yield). MS (ESI): m / z = 250.0 [M-Bu+H] + 。

[0983] Step b) tert-Butyl 6-[[4-(trifluoromethyl)-1,2,3-triazol-2-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[0984] To a mixture of 4-(trifluoromethyl)-1H-1,2,3-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-((methylsulfonyloxy)methyl)-2-azaspiro[3.3]heptane-2-carboxylate (6.0 g, 19.65 mmol, 1 eq, CAS 2740574-92-7). The reaction mixture was stirred at 50 °C for 18 h, filtered, and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 220 g, heptane containing 0% to 100% MTBE) to afford the light-colored title compound (2.5 g, 36% yield), which was a yellow solid. MS (ESI): m / z = 247.0 [M+H - Boc] + 。

[0985] Similar to Example P.50, the following structural units were generated using the relevant commercial structural units in step a). In some cases, sodium iodide was used instead of lithium bromide in step a).

[0986]

[0987] Example P.62

[0988] 6-[[3-(Difluoromethyl)-1H-pyrazol-5-yl]methyl]-2-azaspiro[3.3]heptane; 2,2,2-trifluoroacetic acid

[0989]

[0990] 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) at 0 °C was added 2,2,2-trifluoroacetic acid (20 mL). The mixture was stirred at 20 °C for 16 h. The reaction mixture was concentrated in vacuo. The residue was purified by preparative HPLC to afford the title compound (3.94 g, 87% yield), which was a white solid. MS (ESI): m / z = 228.2 [M+H] + 。

[0991] Step a) tert-butyl 6-[[5-(difluoromethyl)-2-(2-trimethylsilylethoxymethyl)pyrazol-3-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate

[0992] In N 2Under the condition, cyclopentadien-2,4-dien-1-yl(diphenyl)phosphine; dichloromethane; palladium(II) dichloride; iron(2+) (1.32 g, 1.62 mmol, 0.1 eq, CAS 95464-05-4) was added to a mixture of 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 2763647-64-7) and potassium carbonate (4.47 g, 32.4 mmol) in 1,4-dioxane (50 mL) and water (5 mL). The mixture was stirred at 100 °C for 2 h under N 2 atmosphere. The reaction mixture was poured into water (500 mL). The aqueous phase was extracted with EtOAc (300 mL × 2). The organic phase was washed with brine (600 mL), dried over anhydrous Na 2 SO 4 , filtered, and concentrated in vacuo. 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, yield 79%), which was a pale yellow solid. MS (ESI): m / z = 456.3 [M+H] + .

[0993] Step b) tert-butyl 6-[[5-(difluoromethyl)-2-(2-trimethylsilylethoxymethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[0994] Under N 2 atmosphere, 10% Pd / C (2 g, 4.61 mmol, 0.3 eq) was added 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 EtOAc (100 mL). The mixture was stirred at 25 °C for 0.5 h under H 2 (15 PSI) atmosphere. The reaction mixture was filtered and concentrated in vacuo to give tert-butyl 6-[[5-(difluoromethyl)-2-(2-trimethylsilylethoxymethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (6 g, yield 85%), which was a colorless oil.

[0995] Example B.376

[0996] 6-[1-Methyl-3-(trifluoromethyl)pyrazol-4-yl]oxy-2-azaspiro[3.3]heptane; 2,2,2-trifluoroacetic acid

[0997]

[0998] 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 was added trifluoroacetic acid (0.4 mL, 5.23 mmol). The resulting mixture was stirred at 20 °C for 10 h and concentrated. The residue was triturated with Et 2 O, and the precipitated solid was filtered and dried to give the title compound (254 mg, 0.68 mmol, 75.1% yield), which was a white solid. MS m / z: 262.2 [M - TFA + H] +

[0999] Step a) tert-butyl 6-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]oxy-2-azaspiro[3.3]heptane-2-carboxylate

[1000] 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. Under Ar, a solution of diisopropyl azodicarboxylate (1.2 mL, 6.1 mmol) in THF (2 mL) was added dropwise. 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 gel, TBME containing 0% to 100% DCM) to give the title compound (315 mg, 0.87 mmol, 18.6% yield), which was a white solid. MS m / z: 306.0 [M - C 4 H 8 + H] +

[1001] Similar to Example B.376, the following structural units were generated using the relevant commercial structural units in step a).

[1002]

[1003]

[1004] Example B.349

[1005] 3-(2-Azaspiro[3.3]heptan-6-ylmethyl)-5-(trifluoromethyl)-1,2,4-thiadiazole; 4-Methylbenzenesulfonic acid

[1006]

[1007] 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), which was a white solid. MS (ESI): m / z = 264.0 [M - TsOH + H] +

[1008] Step a) tert-Butyl 6-(cyanomethyl)-2-azaspiro[3.3]heptane-2-carboxylate

[1009] Potassium cyanide (2.45 g, 37.7 mmol) was added 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) at room temperature. The reaction solution was stirred at 80 °C for 18 h. The reaction was quenched with water (50 mL) and then extracted with TBME (3 x 100 mL). The organic layer was washed with brine and dried over Na 2 SO 4 and filtered, and concentrated in vacuo to give the title compound (3.4 g, 14.4 mmol, 83.6% yield), which was a white solid. MS (ESI): m / z = 181.0 [M - C 4 H 8 + H] + .

[1010] Step b) tert-Butyl 6-[2-(hydroxyamino)-2-imino-ethyl]-2-azaspiro[3.3]heptane-2-carboxylate

[1011] At 25 °C, TEA (3426 mg, 33.9 mmol) was added to a mixture of hydroxylamine hydrochloride (2353 mg, 33.9 mmol) in ethanol (25 mL). 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 then the reactants were stirred at 50 °C for another 12 h. The reaction was concentrated under reduced pressure to obtain a residue. The residue was dissolved in water (50.0 mL), extracted with ethyl acetate (50.0 mL x 3), and the combined extracts were concentrated under reduced pressure to obtain the title compound (4.5 g, 16.7 mmol, 98.7% yield), which was a colorless oil and was used in the next step without further purification. MS (ESI): m / z = 270.1 [M+H] +

[1012] Step c) tert-butyl 6-(2-amino-2-imino-ethyl)-2-azaspiro[3.3]heptane-2-carboxylate; acetic acid

[1013] At 25 °C, Pd / C (wet) (1.2 g) was added 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 Ac 2 O (2.56 g, 25.1 mmol) in acetic acid (20 mL). Then the reaction was stirred at 25 °C for 12 h under an H 2 atmosphere (H 2 balloon). The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to obtain the crude title compound (5.2 g, 16.6 mmol, 99.3% yield), which was a light yellow oil. MS (ESI): m / z = 254.0 [M - AcOH + H] +

[1014] Step d) tert-butyl 6-[(5-amino-1,2,4-thiadiazol-3-yl)methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[1015] At 0 °C, sodium hypochlorite (15.0 mL, 10.5 mmol) was added dropwise 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), and then the mixture was stirred at 20 °C for 1 h, then diluted with water and extracted with EtOAc (20 mL x 3). The combined organic phases were passed through Na 2 SO 4Dry and concentrate. Dissolve the residue in methanol (30 mL), add potassium thiocyanate (1023 mg, 10.5 mmol) at 0 °C, and then stir the solution at 20 °C for 11 h. Filter the reaction mixture, concentrate the filtrate under reduced pressure to obtain a residue. Purify the residue by silica gel column (ethyl acetate: petroleum ether 0% to 80%) and concentrate under reduced pressure to obtain the title compound (1400 mg, 4.51 mmol, yield 47.1%), which is a brown solid. MS (ESI): m / z = 311.0 [M+H] +

[1016] Step e) tert-Butyl 6-[(5-iodo-1,2,4-thiadiazol-3-yl)methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[1017] At 25 °C, add a solution of tert-butyl nitrite (930 mg, 9.02 mmol, 2.0 eq) in MeCN (5 mL) 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), and then stir the reaction at 70 °C for 12 h under N 2 atmosphere. Filter the reaction mixture, concentrate the filtrate under reduced pressure to obtain a residue. Purify the residue by silica gel column (ethyl acetate: petroleum ether 0% to 40%) and concentrate under reduced pressure to obtain the title compound, which is a yellow solid (900 mg, 2.14 mmol, yield 47.4%). MS (ESI): m / z = 421.9 [M+H] +

[1018] Step f) tert-Butyl 6-[[5-(trifluoromethyl)-1,2,4-thiadiazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[1019] 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 for 12 h under N 2 atmosphere. Filter the reaction mixture, concentrate the filtrate under reduced pressure to obtain a residue. Purify the residue by reverse-phase flash chromatography (FA conditions; MeCN:H 2Purified with O = 0% to 70%) and lyophilized to obtain a residue. The residue was purified by a silica gel column (ethyl acetate: petroleum ether 0% to 30%) and concentrated under reduced pressure to obtain the title compound (400 mg, 1.1 mmol, yield 52.1%), which was a colorless oil. MS (ESI): m / z = 307.9 [M - C 4 H 8 + H] +

[1020] Example B.377

[1021] 6 - [[4 - [1 - (trifluoromethyl)cyclopropyl]pyrazol - 1 - yl]methyl]-2 - azaspiro[3.3]heptane; 4 - methylbenzenesulfonic acid

[1022]

[1023] 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 EtOAc (8 mL) was stirred at 80 °C for 12 h. The reaction mixture was concentrated and lyophilized to obtain the title compound (467 mg, 1.02 mmol, yield 91%), which was a light brown solid. MS (ESI): m / z = 286.2 [M + H] +

[1024] Step a) tert - butyl 6 - [(4 - bromopyrazol - 1 - yl)methylene]-2 - azaspiro[3.3]heptane - 2 - carboxylate

[1025] 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) 2 (3670 mg, 18.4 mmol). The mixture was stirred at 70 °C under O 2 for 12 h. The reaction mixture was purified by preparative HPLC and lyophilized. The residue was triturated and stirred in petroleum ether (10 mL) for 10 min. The solid was collected by filtration to obtain the title compound (2867 mg, 8.09 mmol, yield 59%), which was an off - white solid. MS (ESI): m / z = 298.1 [M + H] +

[1026] Step b) tert-Butyl 6-[(4-bromopyrazol-1-yl)methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[1027] Under N 2 At 20 °C, 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 EtOAc (25 mL) was added PtO 2 (920 mg, 4.05 mmol), and then the mixture was stirred at 20 °C under H 2 atmosphere (balloon) for 1 h. The precipitate was filtered off, and the filtrate was dried in vacuo. The residue was purified by column chromatography (hexane / EtOAc, 1:1) to give the title compound (2200 mg, 6.18 mmol, 95% yield), which was a light yellow solid.

[1028] MS (ESI): m / z = 302.0 [M - C 4 H 8 + H] +

[1029] Step c) tert-Butyl 6-[[4-[1-(trifluoromethyl)vinyl]pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[1030] Under N 2 At 20 °C, 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), K 2 CO 3 (1980 mg, 14.3 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride (390 mg, 0.48 mmol). The mixture was stirred at 80 °C under N 2 atmosphere for 12 h. The precipitate was filtered off, and the filtrate was concentrated in vacuo. 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), which was a light brown solid. MS (ESI): m / z = 372.1 [M + H] +

[1031] Step d) tert-Butyl 6-[[4-[1-(trifluoromethyl)cyclopropyl]pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[1032] 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), which was a light yellow solid. MS (ESI): m / z = 386.1 [M+H] +

[1033] Similar to Example B.377, the following structural units were generated using the relevant commercial structural units.

[1034]

[1035] Example B.379

[1036] 6-[[1-Cyclopropyl-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptane; 4-methylbenzenesulfonic acid

[1037]

[1038] 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 EtOAc (8 mL) at 25 °C was added p-toluenesulfonic acid (388 mg, 2.25 mmol), and then the reaction mixture was stirred at 80 °C for 12 h. The reaction mixture was concentrated under reduced pressure to give a residue. To the residue was added 20 mL of deionized water and 2 mL of ACN, and then it was lyophilized to give the title compound (811 mg, 1.77 mmol, 85% yield), which was a yellow oil. MS (ESI): m / z = 286.1 [M - TsOH + H] +

[1039] Step a) tert-Butyl 6-[[5-(trifluoromethyl)-1H-pyrazol-4-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate

[1040] At 20 °C, potassium carbonate (3750 mg, 27.2 mmol) and 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (554 mg, 0.68 mmol) were added 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) and 4-bromo-5-(trifluoromethyl)-1H-pyrazole (2920 mg, 13.6 mmol) in 1,4-dioxane (73 mL) and water (14.6 mL), and then the reaction was stirred at 100 °C for 12 h under N 2 The reaction mixture was filtered and concentrated under reduced pressure to give a residue, which was purified by flash silica gel chromatography (eluent: 0% to 40% ethyl acetate / petroleum ether) to give a crude product, which was further purified by flash silica gel chromatography (eluent: 0% to 40% ethyl acetate / petroleum ether) to give the title compound (790 mg, 2.3 mmol, 17% yield), which was a yellow oil. MS (ESI): m / z = 288.0 [M - C 4 H 8 + H] + .

[1041] Step b) tert-butyl 6-[[1-cyclopropyl-3-(trifluoromethyl)pyrazol-4-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate

[1042] At 20 °C, pyridine (0.42 mL, 5.24 mmol), boric acid (108 mg, 1.75 mmol), and copper(II) diacetate (698 mg, 3.5 mmol) were added 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) and cyclopropylboronic acid (600 mg, 6.99 mmol) in DCE (6 mL), and then the reaction mixture was stirred at 100 °C for 16 h under O 2 (balloon). The reaction mixture was filtered, then diluted with 50 mL of water and extracted with 150 mL of EtOAc (50 mL x 3). The combined organic layers were washed with brine (40 mL), dried over Na 2 SO 4 4, filtered and concentrated under reduced pressure to give a residue, which was purified by silica gel chromatography (0% to 28% ethyl acetate / petroleum ether) to give the title compound (350 mg, 0.91 mmol, 52%). MS (ESI): m / z = 328.0 [M - C 4 H 8 + H]+ .

[1043] Step c) tert-Butyl 6-[[(1-cyclopropyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[1044] At 25 °C, Pd / C (wet, 216 mg, 10%) was added to a mixture of tert-butyl 6-[[(1-cyclopropyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)methylene]-2-azaspiro[3.3]heptane-2-carboxylate (720 mg, 1.88 mmol) in EtOAc (15 mL), and then the reaction mixture was stirred at 25 °C under H 2 (15 Psi) for 0.5 h. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to afford the title compound (640 mg, 1.66 mmol, 88.4% yield), which was a colorless oil. MS (ESI): m / z = 330.0 [M - C 4 H 8 + H] + .

[1045] Example B.381

[1046] 6-[[(5-Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl]-2-azaspiro[3.3]heptane; 4-methylbenzenesulfonic acid

[1047]

[1048] A mixture of tert-butyl 6-[[(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl]-2-azaspiro[3.3]heptane-2-carboxylate (3.8 g, 10.57 mmol, 1.0 eq) and p-toluenesulfonic acid (4.55 g, 26.43 mmol, 2.5 eq) in EtOAc (70 mL) was stirred at 25 °C for 24 h. Then the reaction mixture was concentrated and crystallized from MTBE to afford 4-methylbenzenesulfonic acid; 6-[[(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl]-2-azaspiro[3.3]heptane (3940 mg, 9.13 mmol, 86% yield), which was a white solid. MS (ESI): m / z = 260.2 [M + H] +

[1049] Step a) tert-Butyl 6-[[(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[1050] 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 for 12 h under N 2 atmosphere. 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), which was a dark brown powder. MS (ESI): m / z = 304.0 [M+H] +

[1051] Note: The positional isomer 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 formed, which was a dark brown oil. MS (ESI): m / z = 304.0 [M+H] +

[1052] Example B.382

[1053] 6-[[3-Methyl-5-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane; 4-methylbenzenesulfonic acid

[1054]

[1055] A mixture of tert-butyl 6-[[3-methyl-5-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (formed as a positional isomer in step a of B.381) (2.3 g, 6.4 mmol) and p-toluenesulfonic acid (2755 mg, 16.0 mmol) in EtOAc (50 mL) was stirred at 25 °C for 24 h. The reaction mixture was concentrated and crystallized from MTBE to give the title compound (1468 mg, 3.4 mmol, 53% yield), which was a white solid. MS (ESI): m / z = 260.2 [M+H] +

[1056] Similar to Example B.381 / B.382, pairs of positional isomers of the following structural units were generated using the relevant commercial structural units.

[1057]

[1058]

[1059] Example B.390

[1060] 6-(1-Methylpyrazol-4-yl)oxy-2-azaspiro[3.3]heptane; 4-Methylbenzenesulfonic acid

[1061]

[1062] 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 h. The reaction mixture was concentrated under reduced pressure at 20 °C to give the crude product. Then water (15 mL) was added to the crude product. The solution was lyophilized to give the title compound (845 mg, 1.57 mmol, 47% yield), which was a yellow gum. MS (ESI): m / z = 194.2 [M - TsOH + H] +

[1063] Step a) tert-butyl 6-(1-methylpyrazol-4-yl)oxy-2-azaspiro[3.3]heptane-2-carboxylate

[1064] Under a N 2 atmosphere, 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) was added CMBP ((cyanomethylene)tributylphosphine) (6150 mg, 25.5 mmol), and the mixture was stirred at 110 °C for 16 h. The mixture was concentrated in vacuo to give a residue, which was purified by flash silica 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), which was obtained as a yellow solid. MS (ESI): m / z = 238.2 [M - C 4 H 8 + H] +

[1065] Example B.400

[1066] 3-(2-Azaspiro[3.3]heptan-6-ylmethyl)-5-(trifluoromethyl)-1,2,4-oxadiazole; 4-Methylbenzenesulfonic acid

[1067]

[1068] 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 p-toluenesulfonic acid TsOH (208 mg, 1.21 mmol) in ethyl acetate (10 mL) was stirred at 80 °C for 12 h. 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), which was a white solid. MS (ESI): m / z = 248.0 [M - TsOH + H] +

[1069] Step a) tert-butyl 6-[(2Z)-2-amino-2-hydroxyimino-ethyl]-2-azaspiro[3.3]heptane-2-carboxylate

[1070] To a mixture of hydroxylamine; hydrochloride (2353 mg, 33.9 mmol) in ethanol (25 mL) at 25 °C was added TEA (3426 mg, 33.9 mmol). After 1 h, 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 then the reaction was stirred at 50 °C for another 12 h. The reaction was concentrated under reduced pressure to give a residue. The residue was dissolved in water (50 mL), extracted with ethyl acetate (50 mL x 3), and the combined extracts were concentrated under reduced pressure to give the title compound (4.5 g, 16.7 mmol, 99% yield), which was a colorless oil and was used in the next step without further purification. MS (ESI): m / z = 270.1 [M + H] +

[1071] Step b) tert-butyl 6-[[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[1072] At 30 °C, 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). The reaction was then stirred at 50 °C for 12 h. The reaction was concentrated under reduced pressure to give a residue. The residue was dissolved in water (20 mL), the reaction mixture was extracted with ethyl acetate (10 mL x 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, yield 34.9%), which was a colorless oil. MS(ESI): m / z = 292.0 [M - C 4 H 8 +H] +

[1073] Example B.408

[1074] 6-[[1-(2,2,2-Trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptane; 4-methylbenzenesulfonic acid

[1075]

[1076] At 20 °C, 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 EtOAc (10 mL) was added p-toluenesulfonic acid (465 mg, 2.7 mmol), and then the reaction mixture was stirred at 80 °C for 12 h. The reaction mixture was concentrated under reduced pressure to give a residue. Then 20 mL of deionized water and 2 mL of ACN were added to the residue. The mixture was lyophilized to give the title compound (1224 mg, 2.45 mmol, yield 99%), which was a light yellow oil. MS(ESI): m / z = 328.0 [M + H] + 。

[1077] Step a) tert-butyl 6-[[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate

[1078] At 0 °C, a solution of 2,2,2-trifluoroethyl trifluoromethanesulfonate (2704 mg, 11.7 mmol) in DMF (2 mL) was added 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), cesium carbonate (5694 mg, 17.5 mmol) in DMF (20 mL), and the mixture was stirred at 20 °C for 12 h. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (100 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to give a residue which was purified by flash silica chromatography (eluent 0% to 28% ethyl acetate / petroleum ether) to give the title compound (1.1 g, 2.59 mmol, 44% yield), which was a white solid. MS (ESI): m / z = 370.0 [M - C 4 H 8 + H] + .

[1079] Step b) tert-butyl 6-[[1-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[1080] At 20 °C, Pd / C (300 mg, 10%, wet) was added 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 EtOAc (10 mL), and then the reaction mixture was stirred at 20 °C under H 2 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), which was a colorless oil. MS (ESI): m / z = 372.0 [M - C 4 H 8 + H] + .

[1081] Example B.409

[1082] 6-[(3-Cyclopropyl-1H-pyrazol-5-yl)methyl]-2-azaspiro[3.3]heptane; 2,2,2-trifluoroacetic acid

[1083]

[1084] To a solution of tert-butyl 6-[(3-cyclopropyl-1H-pyrazol-5-yl)methyl]-2-azaspiro[3.3]heptane-2-carboxylate (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 RT for 18 h. Volatiles were removed in vacuo to afford 374 mg of the crude title compound, which was used without further purification, with a purity of approximately 50%, and the major contaminant was excess TFA. MS (ESI): m / z = 218.2 [M-TFA + H] + 。

[1085] Step a) tert-butyl 6-(4-cyclopropyl-2,4-dioxo-butyl)-2-azaspiro[3.3]heptane-2-carboxylate

[1086] 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) at 25 °C was added NaH (791 mg, 19.8 mmol). After 0.5 h, methyl cyclopropyl 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 the addition of H 2 O (10 mL), then diluted with H 2 O (10 mL) and extracted with EtOAc (10 mL x 3). The combined organic layers were washed with saturated aqueous NaCl solution (10 mL x 3), dried over anhydrous Na 2 SO 4 4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by preparative TLC (SiO 2 2, petroleum ether / ethyl acetate = 3:1) to afford the title compound (600 mg, 1.87 mmol, 26% yield), which was a yellow oil. MS (ESI): m / z = 266.2 [M - C 4 H 8 3 + H] + 。

[1087] Step b) tert-butyl 6-[(5-cyclopropyl-1H-pyrazol-3-yl)methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[1088] At 20 °C, hydrazine (108 mg, 3.36 mmol) was added 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), 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), which was a colorless oil. MS (ESI): m / z = 262.1 [M - C 4 H 8 + H] + 。

[1089] Example B.414

[1090] 5-(2-Azaspiro[3.3]heptan-6-ylmethyl)-3-(trifluoromethyl)-1,2,4-oxadiazole; 4-methylbenzenesulfonic acid

[1091]

[1092] At 80 °C, p-toluenesulfonic acid (70.2 mg, 0.41 mmol) was added 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 EtOAc (2 mL), and the mixture was stirred for 12 h. The mixture was concentrated under reduced pressure to give a residue. Deionized water was added to the residue and lyophilized to give the title compound (125 mg, 0.3 mmol, 84% yield), which was a white solid. MS (ESI): m / z = 248.1 [M - TsOH + H] +

[1093] Step a) tert-Butyl 6-[[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[1094] At 25 °C, a solution of sodium methoxide in MeOH (5 M) (0.42 mL, 2.12 mmol) was added 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), and then the mixture was stirred at 60 °C for 12 h. The residue was purified by preparative HPLC and lyophilized to give the title compound (120 mg, 0.35 mmol, 33% yield), which was a yellow oil. 11H 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 - C 4 H 8 + H] + Example B.415

[1095] 6 - [[2-(2,2,2-Trifluoroethyl)-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane; 4-Methylbenzenesulfonic acid

[1096]

[1097] 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 h. The mixture was concentrated under reduced pressure to give a residue. Deionized water was added to the residue and freeze-dried to give the title compound (550 mg, 1.1 mmol, yield 92.3%), which was a colorless oil. MS (ESI): m / z = 328.0 [M - TsOH + H] +

[1098] Step a) tert-Butyl 6-[[2-(2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[1099] To a solution of tert-butyl 6-[[5-(trifluoromethyl)-1H-pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (generated in the synthesis of step P.7 c) (1.5 g, 4.34 mmol) in THF (15 mL) at 0 °C was added NaH (261 mg, 6.51 mmol) over 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 phases were washed with brine (20 mL × 3) and dried over anhydrous Na 2 SO 4Dry, filter, and concentrate in vacuo. Purify the residue by preparative HPLC and lyophilize to afford the positional isomers 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, yield 12.93%) (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, yield 43.1%) (crude), which are yellow solids. Purify the residue by preparative HPLC to afford the title compound (530 mg, 1.24 mmol, yield 66%), which is a colorless oil. MS (ESI): m / z = 372.0 [M - C 4 H 8 + H] +

[1100] Example B.416

[1101] 6-[[1-(2,2,2-Trifluoroethyl)-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane; 4-methylbenzenesulfonic acid

[1102]

[1103] 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 (positional isomer product from step a of B.415) (90.0 mg, 0.21 mmol) in EtOAc (2 mL) was stirred at 80 °C for 12 h. The mixture was concentrated under reduced pressure to afford a residue. Deionized water was added to the residue and lyophilized to afford 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, yield 88.31%), which is an off-white solid. MS (ESI): m / z = 328.0 [M - TsOH + H] + ; 1HNMR (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)

[1104] Example B.443

[1105] 6 - [[3-(2,2,2-Trifluoroethyl)-1H-1,2,4-triazol-5-yl]methyl]-2-azaspiro[3.3]heptane; 2,2,2-trifluoroacetic acid

[1106]

[1107] To a solution of tert-butyl 6-[[5-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (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 RT for 18 h. Volatiles were removed in vacuo to afford 318 mg of the crude title compound as a viscous yellow oil with a purity of about 50%, the major contaminant being excess TFA, which was used without further purification. MS (ESI): m / z = 261.2 [M - TFA + H] +

[1108] Step a) tert-butyl 6-[[5-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[1109] Under N 2 atmosphere, at 25 °C, EtONa (195 mg, 2.87 mmol) was added to a solution of 3,3,3-trifluoropropanohydrazide (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). The reaction was then carried out under N 2Stirred at 100 °C for 12 h under an atmosphere. The reaction was purified by preparative HPLC and lyophilized to afford the title compound (200 mg, 0.55 mmol, 29% yield), which was a white solid. MS (ESI): m / z = 361.1 [M+H] +

[1110] 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)

[1111] Example B.526

[1112] 5-(2,6-Diazaspiro[3.3]heptan-2-ylmethyl)-3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazole; trifluoroacetic acid

[1113]

[1114] To a solution of tert-butyl 6-[[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptane-2-carboxylate (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 RT for 18 h. Volatiles were removed in vacuo to afford 478 mg of the crude desired product as a pale yellow viscous oil with a purity of approximately 50%, the major contaminant being excess TFA. The crude product was used without further purification. MS (ESI): m / z = 289.2 [M+H] +

[1115] 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

[1116] 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 h. N'-Hydroxy-1-(trifluoromethyl)cyclopropanecarboximidamide (CAS: 2172624-76-7) (951 mg, 5.66 mmol) was added to the solution and stirred at 30 °C for 12 h. The reaction was purified by preparative HPLC (water (NH 4 HCO 3 )-ACN 27% to 57%) to give the title compound (670 mg, 1.65 mmol, 29% yield), which is a white solid. MS (ESI): m / z = 407.1 [M+H] + ; 1 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)

[1117] Step b) tert-Butyl 6-[[3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptane-2-carboxylate

[1118] 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 Bu 4 NF (0.37 mL, 0.37 mmol, 0.25 eq) 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 a crude product. The crude product was purified by preparative HPLC (water (FA)-ACN 18% to 48%) to give the title compound, which is a yellow solid (260 mg, 0.67 mmol, 43% yield). MS (ESI): m / z = 389.0 [M+H] + ; 1 1H 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).

[1119] Example B.528

[1120] 6-[(4-Methylsulfonylpyrazol-1-yl)methyl]-2-azaspiro[3.3]heptane; 4-methylbenzenesulfonic acid

[1121]

[1122] 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 under an N 2 balloon at 80 °C for 12 h. 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), which was 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). Step a) tert-Butyl 6-[(4-iodopyrazol-1-yl)methylene]-2-azaspiro[3.3]heptane-2-carboxylate

[1123] Under an O 2 atmosphere, copper(II) diacetate (49.4 g, 247 mmol) was added 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). The mixture was stirred under an O 2Stir at 70 °C for 12 h under an atmosphere. Concentrate the reaction product. Purify the residue by flash chromatography on silica gel, eluting with PE / EtOAc (4:1) to obtain the crude product, which is purified by preparative HPLC (water (FA)-ACN 55% to 75%) to obtain the title compound as a white solid (17.7 g, 44.1 mmol, yield 35.6%). MS (ESI): m / z = 346.0 [M - C 4 H 8 + H] +

[1124] Step b) tert-Butyl 6-[(4-methylsulfonylpyrazol-1-yl)methylene]-2-azaspiro[3.3]heptane-2-carboxylate

[1125] 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 eq) in DMSO (30 mL) at 110 °C, add sodium methanesulfonate (1.18 g, 9.97 mmol, 2.0 eq), Cu(OTf) 2 (361 mg, 1.0 mmol) and (R,R)-1,2-bis(N-methylamino)cyclohexane (142 mg, 1.0 mmol) for 12 h. Concentrate the reaction and purify the residue by flash chromatography on silica gel, eluting with PE / EtOAc (1:2) to obtain the title compound as a white solid (1.45 g, 4.1 mmol, yield 82%). MS (ESI): m / z = 298.1 [M - C 4 H 8 + H] +

[1126] Step c) tert-Butyl 6-[(4-methylsulfonylpyrazol-1-yl)methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[1127] 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 EtOAc (50 mL) at 25 °C, add Pd / C (0.5 g, 0.35 mmol), and stir under a H 2 balloon (760 mm Hg) for 1 h. Filter and concentrate the reaction to obtain the title compound (1.15 g, 3.24 mmol, yield 91%) as a white solid. MS (ESI): m / z = 300.3 [M - C 4 H 8 + H] +

[1128] Example B.529

[1129] 6-[[4-(Trifluoromethylsulfonyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane 4-methylbenzenesulfonate

[1130]

[1131] 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 eq) in EtOAc (20 mL) was stirred under a N 2 balloon at 80 °C for 12 h. The reaction was concentrated and the residue was dissolved in H 2 O (30 mL). The solution was lyophilized to afford the title compound (738 mg, 1.53 mmol, 97% yield), which was a light yellow solid. MS (ESI): m / z = 310.1 [M+H] +

[1132] Step a) tert-Butyl 6-[[4-(trifluoromethylthio)pyrazol-1-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate

[1133] In a sealed tube, 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) were added 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) at 90 °C for 12 h. The reaction was concentrated. The residue was purified by preparative HPLC (water (FA)-ACN] 52% to 82%) to afford the title compound (13.0 mg, 0.03 mmol, 46% yield), which was a yellow solid. MS (ESI): m / z = 320.1 [M-C 4 H 8 +H] +

[1134] Step b) tert-Butyl 6-[[4-(trifluoromethylthio)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[1135] At 25 °C, Pd / C (1.0 g, 0.75 mmol) was added to a solution of tert-butyl 6-[[4-(trifluoromethylthio)pyrazol-1-yl]methylene]-2-azaspiro[3.3]heptane-2-carboxylate (2.8 g, 7.46 mmol) in EtOAc (50 mL), and the mixture was stirred under a H 2 balloon (760 mmHg) for 1 h. The reaction was filtered and concentrated to afford the title compound (2.8 g, 7.42 mmol, 99% yield), which was a white solid. MS (ESI): m / z = 322.2 [M - C 4 H 8 + H] +

[1136] Step c) tert-butyl 6-[[4-(trifluoromethylsulfonyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[1137] At 0 °C, sodium periodate (1.13 g, 5.3 mmol) and ruthenium(III) chloride hydrate (59.7 mg, 0.26 mmol) were added to a solution of tert-butyl 6-[[4-(trifluoromethylthio)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). Then the mixture was 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), which was a gray solid. MS (ESI): m / z = 354.3 [M - C 4 H 8 + H] +

[1138] Example B.530

[1139] [1-(2-azaspiro[3.3]heptan-6-ylmethyl)pyrazol-4-yl]-imino-oxo-(trifluoromethyl)-λ 6 -sulfane; 4-methylbenzenesulfonic acid

[1140]

[1141] A mixture of tert-butyl 6-[[4-(trifluoromethylsulfinyl)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 placed under N 2The balloon was stirred at 80 °C for 12 h. The reaction was concentrated, and the residue was dissolved in H 2 O (30 mL). The solution was lyophilized to give the title compound (623 mg, 1.3 mmol, 77% yield), which was a pale yellow oil. MS (ESI): m / z = 309.1 [M+H] +

[1142] Step a) tert-Butyl 6-[[4-(trifluoromethylsulfinyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[1143] A mixture of tert-butyl 6-[[4-(trifluoromethylthio)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carboxylate (B.529, step b) (1.8 g, 4.77 mmol), PhI(OAc) 2 (6.14 g, 19.1 mmol) and NH 2 COONH 4 (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% to 80%) to give the title compound (650 mg, 1.59 mmol, 33% yield), which was a gray solid. MS (ESI): m / z = 353.1 [M - C 4 H 8 +H] +

[1144] Example C.10

[1145] 3-Bromo-5-[1-(trifluoromethyl)cyclopropyl]-1H-1,2,4-triazole

[1146] 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 Na 2 SO 4 and concentrated in vacuo. The crude material was purified by flash chromatography (heptane containing 0% to 20% AcOEt) to give the title compound (3.08 g, 42.0%), which was a white solid. MS (ESI): m / z = 255.9 / 257.9 [M+H] +

[1147] Step a) (NE)-N-(dimethylaminomethylene)-1-(trifluoromethyl)cyclopropanecarboxamide

[1148] Dissolve 1-(trifluoromethyl)cyclopropanecarboxamide (5.0 g, 32.7 mmol) in N,N-dimethylformamide dimethyl acetal (27.2 g, 30.4 mL, 229 mmol). Stir the mixture at RT for 6 h. Pour the reaction mixture into EtOAc and wash with water (three times) and brine. Dry the organic layer over Na 2 SO 4 and concentrate in vacuo to afford the title compound (6.5 g, 90.8%) as a yellow amorphous solid. MS (ESI): m / z = 209.1 [M+H] +

[1149] Step b) 3-[1-(trifluoromethyl)cyclopropyl]-1H-1,2,4-triazole

[1150] To a solution of ice-cold (NE)-N-(dimethylaminomethylene)-1-(trifluoromethyl)cyclopropanecarboxamide (6.5 g, 28.1 mmol) in acetic acid (18 mL) is added hydrazine hydrate (1.55 g, 1.5 mL, 30.9 mmol). Stir the mixture at RT for 2 h and then at 50 °C for 2 h. Concentrate the reaction mixture in vacuo and dissolve in EtOAc. Add 1N aqueous NaOH (pH 7 to 8). Wash the mixture with water and brine. Dry the organic layer over Na 2 SO 4 and concentrate in vacuo to afford the title compound (5.07 g, 96.8%) as a yellow oil. MS (ESI): m / z = 178.1 [M+H] +

[1151] Example C.11

[1152] 4,5-Dibromo-2-(2,2,2-trifluoroethyl)-1,2,4-triazole

[1153] To a solution of 4,5-dibromo-2H-1,2,4-triazole (5.0 g, 22.0 mmol) in ACN (50 mL) is added cesium carbonate (7.18 g, 22.0 mmol). Then, 2,2,2-trifluoroethyl trifluoromethanesulfonate (5.12 g, 22.0 mmol) is added dropwise at 0 °C. Stir the reaction mixture at RT for 16 h. Pour the reaction mixture into water, add EtOAc, and extract the aqueous layer with EtOAc three times. Then, wash the combined organic layers with water and brine, dry over Na 2 SO 4Dry, filter and evaporate. Purify the crude product by column chromatography (silica gel, PE / EtOAc 0% to 7%). Combine the fractions containing the pure product and evaporate to give 4,5-dibromo-2-(2,2,2-trifluoroethyl)-1,2,4-triazole (5.3 g, 17.2 mmol, 77.9% yield), which is a yellow oil. 1 H NMR (400 MHz, chloroform-d) δ = 4.95 (q, J = 7.9 Hz, 2H)

[1154] Example C.12

[1155] 3-Bromo-1-(2,2,2-trifluoroethyl)-1,2,4-triazole

[1156] To a solution of 3-bromo-1H-1,2,4-triazole (8000 mg, 54.1 mmol) in THF (80 mL) at 0 °C was added NaH (3.89 g, 97.3 mmol). 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 Na 2 SO 4 dried, filtered and concentrated in vacuo 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), which is 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)

[1157] Example C.13

[1158] 4-Dimethylphosphoryl-2-methyl-pyrazole-3-carbaldehyde

[1159] 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 eq), Xantphos (981 mg, 1.69 mmol) and Pd 2 (dba) 3 (776 mg, 0.85 mmol). The reaction mixture was placed under N2 Stir at 70 °C for 12 h under an atmosphere. Filter the reaction mixture and concentrate the filtrate under reduced pressure to obtain a residue. Purify the residue by reverse-phase flash chromatography (FA conditions; MeCN:H 2 O = 0% to 30%) and lyophilize to obtain the light-colored title compound, which is a yellow solid. MS (ESI): m / z = 187.0 [M+H] + ; 1 1H NMR (400 MHz, chloroform-d) δ ppm 1.81 (s, 3H) 1.84 (s, 3H) 4.25 (s, 3H) 7.60 (br d, J = 1.83 Hz, 1H) 10.49 (s, 1H).

[1160] Example C.17

[1161] 3-Bromo-5-[1-(trifluoromethyl)cyclopropyl]-1H-pyrazole

[1162] At 0 °C, a solution of isopentyl nitrite (1.55 g, 13.2 mmol) in ACN (5 mL) was added dropwise to a solution of 5-[1-(trifluoromethyl)cyclopropyl]-1H-pyrazol-3-amine (2.3 g, 12.0 mmol) in ACN (40 mL). Stir the reaction at 0 °C for 1 h. Then add CuBr 2 (1.61 g, 7.22 mmol) to the mixture and stir the resulting mixture at 20 °C for 12 h. Concentrate the reaction mixture under reduced pressure to obtain a residue. Purify the residue by reverse-phase HPLC (water (0.1% FA)-ACN]). Lyophilize the purified solution to obtain the title compound (740 mg, 2.9 mmol, 24.1% yield), which is a light green solid. MS (ESI): m / z = 257.2 [M+H] + .

[1163] Example C.22

[1164] 1-(3,3,3-Trifluoropropyl)pyrazole-3-carbaldehyde

[1165] To a solution of 1H-pyrazole-3-carbaldehyde (5.0 g, 52.0 mmol) in N,N-dimethylformamide (100 mL) was added 1,1,1-trifluoro-3-iodopropane (17.5 g, 78.1 mmol), Cs 2 CO 3(33.9 g, 104 mmol, 2.0 eq) and 18-crown-6 (6.88 g, 26.02 mmol, 0.5 eq). 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 x 3). The combined organic layers were washed with brine (100 mL), dried over Na 2 SO 4 , 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), which was a yellow oil. MS (ESI): m / z = 193.1 [M+H]; 1 1H 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).

[1166] Example C.23

[1167] 2-[[2-Bromo-4-(trifluoromethyl)imidazol-1-yl]methoxy]ethyl-trimethyl-silane

[1168] 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 reverse-phase flash chromatography (FA conditions; MeCN:H 2 2O 0% to 70%) and lyophilized to give the title compound (21.0 g, 60.8 mmol, 54% yield), which was a yellow oil. MS (ESI): m / z = 346.9 [M+H] + ; 11H 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)

[1169] Example 361

[1170] The compound of formula (I) can be used, in a manner known per se, as an active ingredient for producing tablets having the following composition:

[1171]

[1172] Example 362

[1173] The compound of formula (I) can be used, in a manner known per se, as an active ingredient for producing capsules having the following composition:

[1174]

[1175]

Claims

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein: W and Z are each independently selected from CH 2 and CH 2 CH 2 ; 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 C, H 2 and O; A is selected from: B is selected from: and a 9-membered fused bicyclic heteroaryl group containing 1 to 3 heteroatoms selected from N, O, and S, with the remaining ring atoms being carbon; R 1 selected from 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 and (C 1 -C 6 -alkyl) 2 PO-; R 1a selected from C 1 -C 6 -alkyl and halo-C 1 -C 6 -alkyl; R 2 selected from 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 selected from 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 -alkoxy.

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

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

6. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 5, wherein B is selected from:

7. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 6, wherein B is selected from:

8. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 7, wherein B is selected from:

9. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 8, wherein L is CH 2 .

10. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 9, wherein: R 1 selected from 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 and (C 1 -C 6 -alkyl) 2 PO-; R 1a selected from C 1 -C 6 -alkyl and halo-C 1 -C 6 -alkyl; and X is selected from NH and O.

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

12. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 10, wherein: R 1 Selected from halo-C 1 -C 6 -alkyl, C 3 -C 10 -cycloalkyl, halo-C 1 -C 6 -alkyl-C 3 -C 10 -cycloalkyl and the group R 1a is a halo-C 1 -C 6 -alkyl; and X is selected from NH and O.

13. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 12, wherein: R 1 selected from CHF 2 , CF 3 , 2,2,2-trifluoroethyl, cyclopropyl, (CF 3 ) cyclopropyl and the group R 1a is CF 3 ; and X is selected from NH and O.

14. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 13, wherein: R 1 selected from CF 3 , cyclopropyl, (CF 3 ) cyclopropyl and the group R 1a is CF 3 ; and X is selected from NH and O.

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

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

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

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

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

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

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

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

23. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 1, wherein: W and Z are each independently selected from CH 2 and CH 2 CH 2 ; 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 C and H 2 and O; A is selected from B is selected from: R 1 Selected from 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 and (C 1 -C 6 -alkyl) 2 PO-; R 1a selected from C 1 -C 6 -alkyl and halo-C 1 -C 6 -alkyl; R 2 selected from hydrogen, C 1 -C 6 -alkyl, and halo-C 1 -C 6 -alkyl; and R 3 selected from C 3 -C 10 -cycloalkyl, hydroxy-C 3 -C 10 -cycloalkyl, amino-C 3 -C 10 -cycloalkyl, halo-C 1 -C 6 -alkyl.

24. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 23, wherein: Both W and Z are CH 2 ; or Both W and Z are CH 2 CH 2 ; Y is selected from CH and N; X is selected from NH and O; L is CH 2 ; A is selected from B is selected from: R 1 selected from halo-C 1 -C 6 -alkyl, C 3 -C 10 -cycloalkyl, halo-C 1 -C 6 -alkyl-C 3 -C 10 -cycloalkyl and the group R 1a is halo-C 1 -C 6 -alkyl; R 2 selected from hydrogen, C 1 -C 6 -alkyl and halo-C 1 -C 6 -alkyl; and R 3 Selected from C 3 -C 10 -cycloalkyl, hydroxy-C 3 -C 10 -cycloalkyl, halo-C 1 -C 6 -alkyl.

25. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 24, wherein: Both W and Z are CH 2 ; or Both W and Z are CH 2 CH 2 ; Y is selected from CH and N; X is selected from NH and O; L is CH 2 ; A is selected from B is selected from: R 1 selected from CHF 2 , CF 3 , 2,2,2-trifluoroethyl, cyclopropyl, (CF 3 ) cyclopropyl and the group R 1a is CF 3 ; R 2 selected from hydrogen, methyl and CF 3 ; and R 3 selected from cyclopropyl, hydroxycyclopropyl, and CF 3 .

26. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 1, 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)-1,2,4-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)-1,2,4-triazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(2,2,2-Trifluoroethyl)-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-[[1-(2,2,2-trifluoroethyl)-1H-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)-1H-pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[3-Methyl-1-(2,2,2-trifluoroethyl)-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-[[3-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[5-Methyl-1-(2,2,2-trifluoroethyl)-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-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-methylpyrazol-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-methylpyrazol-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-Cyclopropylpyrazol-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)-1,2,4-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)-1,2,4-triazol-4-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; [6-[[1-(2,2,2-trifluoroethyl)-1H-tetrazol-5-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[6-[3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(2,2,2-trifluoroethyl)-1H-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)-1H-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)-1H-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-1H-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1H-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[2-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1H-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-[6-[[1-(2,2,2-trifluoroethyl)-1H-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)-1H-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[3-(1-hydroxycyclopropyl)-1H-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)-1H-1,2,4-triazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-(3-Cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]-[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-methylsulfonylpyrazol-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-Methylsulfonylpyrazol-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-methylsulfonylpyrazol-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)-1,2,4-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)-1,2,4-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)-1,2,4-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-trifluoromethanesulfonylpyrazol-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-trifluoromethanesulfonylpyrazol-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.

27. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 26, 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)-1,2,4-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)-1,2,4-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)-1,2,4-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-trifluoromethanesulfonylpyrazol-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.

28. A method for preparing a compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 27, said method comprises: reacting a compound of formula 2, wherein A and R 3 as defined in any one of claims 1 to 27, with a compound of formula 1 wherein R 1 , R 2 , B, L, W, Y and Z are as defined in any one of claims 1 to 27, and the reaction is carried out by heating in a solvent such as DMF or CH 3 CN in the presence of a base such as DIPEA to form the compound of formula (I).

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

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

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

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

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

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

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

36. The present invention as described in the specification.

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