Novel heterocyclic-carbonyl-cyclic compounds as MAGL inhibitors

Abstract

The present invention relates to a compound of formula (I)CB(I) TIFF2025525350000373.tif33169 or a pharmaceutically acceptable salt thereof (wherein R 3 ~R 5 , R 4a , B and C are as described herein), compositions comprising the compounds, methods of making the compounds, and methods of using the compounds are provided.

Description

[Technical Field]

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

[0002] Background of the Invention Endocannabinoids (ECs) are signaling lipids that exert their biological effects by interacting with cannabinoid receptors (CBRs), CB1 and CB2. They regulate multiple physiological processes, including neuroinflammation, neurodegeneration, and tissue regeneration (Iannotti, FA, et al., Progress in lipid research 2016, 62, 107-28). In the brain, the main endocannabinoid, 2-arachidonoylglycerol (2-AG), is produced by diacylglycerol lipase (DAGL) and hydrolyzed by monoacylglycerol lipase, MAGL. MAGL hydrolyzes 85% of 2-AG; the remaining 15% is hydrolyzed by ABHD6 and ABDH12 (Nomura, DK, et al., Science 2011, 334, 809). MAGL is expressed throughout the brain and in most brain cell types, including neurons, astrocytes, oligodendrocytes, and microglial cells (Chanda, P.K., et al., Molecular Pharmacology 2010, 78, 996; Viader, A., et al., Cell Reports 2015, 12, 798). Hydrolysis of 2-AG leads to the formation of arachidonic acid (AA), a precursor of prostaglandins (PGs) and leukotrienes (LTs). AA oxidative metabolism is increased in inflamed tissues. Two major enzymatic pathways for arachidonic acid oxidation involved in the inflammatory process are cyclooxygenase, which produces PGs, and 5-lipoxygenase, which produces LTs. Among the various cyclooxygenase products formed during inflammation, PGE2 is one of the most important. These products have been detected at sites of inflammation, for example, in the cerebrospinal fluid of patients with neurodegenerative disorders, and are thought to contribute to the inflammatory response and disease progression. Mice lacking MAGL (Mgll- / -) exhibit dramatically reduced 2-AG hydrolase activity and dramatically elevated 2-AG levels in the nervous system, whereas other arachidonoyl-containing phospholipids and neutral lipid species, including anandamide (AEA), and other free fatty acids, are unchanged.Conversely, levels of AA and AA-derived prostaglandins, as well as other eicosanoids including prostaglandins E2 (PGE2), D2 (PGD2), and F2 (PGF2), and thromboxane B2 (TXB2), are greatly reduced. Although the phospholipase A2 (PLA2) enzyme has been considered the major source of AA, cPLA2-deficient mice have unchanged AA levels in their brains, highlighting the importance of MAGL's role in regulating AA production and brain inflammatory processes.

[0003] Neuroinflammation is a common pathological feature of brain diseases, including, but not limited to, neurodegenerative diseases (e.g., multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, and psychiatric disorders such as anxiety and migraine). In the brain, the production of eicosanoids and prostaglandins regulates the neuroinflammatory process. The inflammatory progenitor lipopolysaccharide (LPS) produces a robust, time-dependent increase in brain eicosanoids that is significantly blunted in Mgll- / - mice. LPS treatment also induces a widespread increase in inflammatory cytokines, including interleukin-1-a (IL-1-a), IL-1b, IL-6, and tumor necrosis factor-a (TNF-a), which are suppressed in Mgll- / - mice.

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

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

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

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

[0008] Furthermore, in recent years, metabolism, especially lipid metabolism, has become increasingly important in cancer research. Researchers believe that de novo fatty acid synthesis plays an important role in tumor development. Many studies have shown that endocannabinoids have antitumor effects, including antiproliferative, apoptosis-inducing, and anti-metastatic effects. MAGL, a key degradative enzyme for both lipid metabolism and the endocannabinoid system, further contributes to various aspects of tumorigenesis, including glioblastoma, as part of gene expression profiles (Qin, H. et al., Cell Biochem. Biophys. 2014, 70, 33; Nomura, DK et al., Cell 2009, 140, 49; Nomura, DK et al., Chem. Biol. 2011, 18, 846; Jinlong, Y. et al., Nat. Commun. 2020, 11, 2978).

[0009] The endocannabinoid system is also involved in many gastrointestinal physiological and physiopathological functions (Marquez, L. et al., PLoS One 2009, 4, e6893). All of these effects are primarily driven through cannabinoid receptors (CB1 and CB2). CB1 receptors are present throughout the gastrointestinal tract in animals and healthy humans, particularly in the enteric nervous system (ENS) and epithelial lining, as well as in smooth muscle cells of blood vessels in the colonic wall (Wright, K. et al., Gastroenterology 2005, 129, 437; Duncan, M. et al., Aliment. Pharmacol. Ther. 2005, 22, 667). CB1 activation provides antiemetic, antimotility, and anti-inflammatory effects and helps regulate pain (Perisetti, A. et al., Ann. Gastroenterol. 2020, 33, 134). CB2 receptors are expressed in immune cells such as plasma cells and macrophages, the lamina propria of the GI tract (Wright, K. et al., Gastroenterology 2005, 129, 437), and the epithelium of human colonic tissue, primarily associated with inflammatory bowel disease (IBD). CB2 activation exerts an anti-inflammatory effect by reducing pro-inflammatory cytokines. MAGL expression is increased in colonic tissue from UC patients (Marquez, L. et al., PLoS One 2009, 4, e6893), and 2-AG levels are increased in the plasma of IBD patients (Grill, M. et al., Sci. Rep. 2019, 9, 2358). Several animal studies have demonstrated the potential of MAGL inhibitors for the symptomatic treatment of IBD. MAGL inhibition prevents TNBS-induced murine colitis and reduces local and circulating inflammatory markers via CB1 / CB2 MoA (Marquez, L. et al., PLoS One 2009, 4, e6893). Furthermore, MAGL inhibition improves intestinal wall integrity and intestinal permeability via CB1-driven MoA (Wang, J. et al., Biochem. Biophys. Res. Commun. 2020, 525, 962).

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

[0011] Summary of the Invention In a first aspect, the present invention provides a compound of formula (I) [ka] or a pharmaceutically acceptable salt thereof, wherein R 3 ~R 5 , R 4a , B and C are as described herein.

[0012] In one aspect, the present invention provides a method of making a compound of formula (IA) or (IB) described herein, comprising: (a) an amine of formula 2, wherein p, q and R 4 are as described herein) [ka] with carboxylic acid 3a (wherein L, A, B, and R 1 ~R 3 are as described herein) [ka] in the presence of a coupling reagent such as CDI, DCC, HATU, HBTU, HOBT, TBTU, T3P or Mukaiyama reagent, and optionally in the presence of a base such as TEA, DIPEA (Huenig base) or DMAP, to give a compound of formula (IB) (wherein A, B, L, p, q, and R 1 ~R 4 is as defined herein) [ka] forming; or (b) an amine of formula 2, wherein p, q and R 4 are as described herein) [ka] with carboxylic acid chloride 3b (wherein L, A, B, and R 1 ~R 3 are as described herein) [ka] in the presence of a base such as TEA, Huenig's base, pyridine, DMAP, or lithium bis(trimethylsilyl)amide to give a compound of formula (IB), 1 ~R 4 is as defined herein); or (c) a first amine of Formula 1, wherein A, B, L, and R 1 ~R 3 are as described herein) [ka] with a second amine 2, wherein X, Y, and Z are as described herein. [ka] in the presence of a base such as sodium bicarbonate and a urea-forming reagent such as bis(trichloromethyl)carbonate, phosgene, trichloromethyl chloroformate, (4-nitrophenyl)carbonate, or 1,1′-carbonyldiimidazole, A compound of formula (IA) 1 ~R 4 is as defined herein) [ka] forming a

[0013] In a further aspect, the present invention provides a compound of formula (I) as described herein when prepared according to the methods described herein.

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

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

[0016] In a further aspect, the present invention provides the use of a compound of formula (I) as described herein or a pharmaceutical composition as described herein for inhibiting monoacylglycerol lipase (MAGL) in a mammal.

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

[0018] In a further aspect, the present invention provides the use of a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein, for the treatment or prevention of multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, anxiety, migraine, depression, hepatocellular carcinoma, colon carcinogenesis, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, pain-associated spasticity, abdominal pain, abdominal pain associated with irritable bowel syndrome, and / or visceral pain in a mammal. DETAILED DESCRIPTION OF THE INVENTION

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

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

[0021] The term "alkoxy" refers to an alkyl group, as defined previously, attached to the parent molecular moiety through an oxygen atom. An alkoxy group contains 1 to 12 carbon atoms, unless otherwise specified. In some preferred embodiments, an alkoxy group contains 1 to 6 carbon atoms ("C 1-6 In other embodiments, alkoxy groups contain 1 to 4 carbon atoms. In still other embodiments, alkoxy groups contain 1 to 3 carbon atoms. Some non-limiting examples of alkoxy groups include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, and tert-butoxy. A particularly preferred, but non-limiting example of alkoxy is methoxy.

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

[0023] As used herein, the term "cycloalkyl" refers to a saturated monocyclic or bicyclic hydrocarbon group of 3 to 10 ring carbon atoms ("C 3-10In some preferred embodiments, the cycloalkyl group is a monocyclic hydrocarbon group of 3 to 8 ring carbon atoms. "Bicyclic cycloalkyl" refers to a cycloalkyl moiety consisting of two saturated carbocyclic rings having two common carbon atoms, i.e., the bridge separating the two rings is either a single bond or a chain of one or two ring atoms, and a spirocyclic moiety, i.e., a cycloalkyl moiety in which the two rings are joined through one common ring atom. Preferably, the cycloalkyl group is a saturated monocyclic hydrocarbon group of 3 to 6 ring carbon atoms, e.g., 3, 4, 5, or 6 carbon atoms. Some non-limiting examples of cycloalkyl include spiro[3.3]heptan-2-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl. Preferred, but non-limiting, examples of cycloalkyl include spiro[3.3]heptan-2-yl and cyclopropyl.

[0024] The terms "heterocyclyl" and "heterocycloalkyl" are used interchangeably herein and refer to a saturated monocyclic or bicyclic, preferably monocyclic, ring system of 3 to 10 ring atoms, preferably 3 to 8 ring atoms, wherein 1, 2, or 3 of the ring atoms are heteroatoms selected from N, O, and S, and the remaining ring atoms are carbon. Preferably, 1 to 2 of the ring atoms are selected from N and O, and the remaining ring atoms are carbon. "Bicyclic heterocyclyl" refers to heterocyclic moieties consisting of two rings that share two ring atoms (i.e., the bridge separating the two rings is either a single bond or a chain of one or two ring atoms) and spirocyclic moieties (i.e., the two rings are connected through one common ring atom). Some non-limiting examples of heterocyclyl groups include azetidin-3-yl, azetidin-2-yl, oxetan-3-yl, oxetan-2-yl, 1-piperidyl, 2-piperidyl, 3-piperidyl, 4-piperidyl, piperazinyl, pyrrolidinyl, oxazolidinyl, dihydropyrazinyl (e.g., 1,2-dihydropyrazin-6-yl), morpholinyl, 2-azaspiro[3.3]heptan-2-yl, 7-azaspiro[3.5]nonan-7-yl, 8-azabicyclo[3.2.1]octan-8-yl, 8-oxa-3-azabicyclo[3.2.1]octane, and 3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl. Preferred, but non-limiting examples of heterocyclyl groups include azetidinyl, piperazinyl, pyrrolidinyl, oxazolidinyl, dihydropyrazinyl, 2-azaspiro[3.3]heptan-2-yl, 7-azaspiro[3.5]nonan-7-yl, 8-azabicyclo[3.2.1]octan-8-yl, and 3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl.

[0025] The term "aryl" refers to a group having a total of 6 to 14 ring members ("C 6-14-aryl"), preferably a monocyclic, bicyclic, or tricyclic carbocyclic ring system having 6 to 12 ring members, more preferably 6 to 10 ring members, wherein at least one ring of the system is aromatic. Some non-limiting examples of aryl include phenyl and 9H-fluorenyl (e.g., 9H-fluoren-9-yl). A particularly preferred, but non-limiting example of aryl is phenyl.

[0026] The term "heteroaryl" refers to a monovalent or polyvalent, monocyclic or bicyclic ring system having a total of 5 to 14 ring members, preferably 5 to 12 ring members, and more preferably 5 to 10 ring members, wherein at least one ring of the system is aromatic and at least one ring of the system contains one or more heteroatoms. Preferably, "heteroaryl" refers to a 5- to 10-membered heteroaryl containing 1, 2, 3, or 4 heteroatoms independently selected from O, S, and N. More preferably, "heteroaryl" refers to a 5- to 10-membered heteroaryl, e.g., a 5-, 6-, 7-, 8-, 9-, or 10-membered heteroaryl containing 1 to 2 heteroatoms independently selected from O, S, and N. Most preferably, "heteroaryl" refers to a 5- to 6-membered heteroaryl containing 1 to 2 heteroatoms independently selected from O, S, and N. Some preferred, but non-limiting examples of heteroaryl include thiazolyl (e.g., thiazol-2-yl); oxazolyl (e.g., oxazol-2-yl); oxadiazolyl; 5,6-dihydro-4H-cyclopenta[d]thiazol-2-yl; 1,2,4-oxadiazol-5-yl; pyridyl (e.g., 2-pyridyl); pyrazolyl (e.g., pyrazol-1-yl); triazolyl; tetrazolyl; pyrazinyl; imidazolyl (e.g., imidazol-1-yl); benzoxazolyl (e.g., benzoxazol-2-yl), 2,3-dihydrobenzofuranyl; and oxazolo[5,4-c]pyridin-2-yl. Some particularly preferred, but non-limiting examples of heteroaryl include oxadiazolyl; pyridyl; triazolyl; tetrazolyl; pyrazinyl and imidazolyl.

[0027] The heterocyclic or heteroaromatic ring can be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure.

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

[0029] The term "amino" refers to the group --NH.sub.2.

[0030] The term "cyano" refers to a -CN (nitrile) group.

[0031] The term "carbamoyl" refers to the group -C(O)-NH2.

[0032] The term "oxo" refers to the group =O.

[0033] The term "carbonyl" refers to the group C=O.

[0034] The term "haloalkyl" refers to an alkyl group in which at least one hydrogen atom of the alkyl group is replaced by a halogen atom, preferably fluoro. Preferably, "haloalkyl" refers to an alkyl group in which one, two, or three hydrogen atoms of the alkyl group are replaced by a halogen atom, most preferably fluoro. Preferred, but non-limiting examples of haloalkyl are fluoromethyl, difluoromethyl, trifluoromethyl, and trifluoroethyl (e.g., 2,2,2-trifluoroethyl). A preferred, but non-limiting example of haloalkyl is trifluoromethyl.

[0035] The term "haloalkoxy" refers to an alkoxy group in which at least one hydrogen atom of the alkoxy group is replaced by a halogen atom, preferably fluoro. Preferably, "haloalkoxy" refers to an alkoxy group in which one, two, or three hydrogen atoms of the alkoxy group are replaced by a halogen atom, most preferably fluoro. Preferred, but non-limiting, examples of haloalkoxy are 2,2,2-trifluoro-1,1-dimethyl-ethoxy, 2,2,2-trifluoroethoxy, and trifluoromethoxy.

[0036] The term "haloaryl" refers to an aryl group, wherein at least one of the hydrogen atoms of the aryl group is replaced by a halogen atom, preferably fluoro or chloro. Preferably, "haloaryl" refers to an aryl group in which one, two, or three hydrogen atoms of the aryl group are replaced by a halogen atom, most preferably fluoro. Preferred, but non-limiting, examples of haloaryl are 4-fluorophenyl, 2-chloro-4-fluorophenyl, 2,6-difluorophenyl, and 3,5-difluorophenyl.

[0037] The term "aryloxy" refers to an aryl group, as defined above, attached to the parent molecular moiety through an oxygen atom. A preferred, but non-limiting example of aryloxy is phenoxy.

[0038] The term "cycloalkyloxy" refers to a cycloalkyl group, as defined above, attached to the parent molecular moiety through an oxygen atom. A preferred, but non-limiting example of cycloalkyloxy is cyclopropoxy.

[0039] The term "heteroaryloxy" refers to a heteroaryl group, as defined above, attached to the parent molecular moiety through an oxygen atom. A preferred, but non-limiting example of heteroaryloxy is pyridyloxy (e.g., 2-pyridyloxy, 3-pyridyloxy, or 4-pyridyloxy).

[0040] The term "heterocyclyloxy" refers to a heterocyclyl group, as defined above, attached to the parent molecular moiety through an oxygen atom. A preferred, but non-limiting example of heterocyclyloxy is azetidinyloxy.

[0041] The term "pharmaceutically acceptable salt" refers to a salt that retains the biological effectiveness and properties of the free base or free acid, without being biologically or otherwise undesirable. Salts are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid (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, and the like. Additionally, these salts can be prepared by adding an inorganic or organic base to the free acid. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, and magnesium salts. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, lysine, arginine, N-ethylpiperidine, piperidine, polyimine resins, etc. A particular pharmaceutically acceptable salt of the compound of formula (I) is the hydrochloride salt.

[0042] The term "protecting group" (PG) refers to a group that selectively blocks a reactive site in a polyfunctional compound so that a chemical reaction, in the sense conventionally associated with synthetic chemistry, can be selectively carried out at an otherwise unprotected reactive site. The protecting group can be removed at an appropriate time. Exemplary protecting groups are amino-protecting groups, carboxy-protecting groups, or hydroxy-protecting groups. Specific protecting groups are tert-butoxycarbonyl (Boc), benzyloxycarbonyl (Cbz), fluorenylmethoxycarbonyl (Fmoc), and benzyl (Bn). Further specific protecting groups are tert-butoxycarbonyl (Boc) and fluorenylmethoxycarbonyl (Fmoc). An even more specific protecting group is tert-butoxycarbonyl (Boc). Exemplary protecting groups and their use in organic synthesis are described, for example, in "Protective Groups in Organic Chemistry," T.W. Greene and P.G.M. Hutts, 5th Ed., 2014, John Wiley & Sons, NY.

[0043] The term "urea-forming reagent" refers to a compound that can react a first amine with a second amine to form a urea derivative. Non-limiting examples of urea-forming reagents include bis(trichloromethyl)carbonate, phosgene, trichloromethyl chloroformate, (4-nitrophenyl)carbonate, and 1,1'-carbonyldiimidazole. The urea-forming reagents described in G. Sartori et al., Green Chemistry 2000, 2, 140 are incorporated herein by reference.

[0044] The compounds of formula (I) may contain several asymmetric centers and may exist as optically pure enantiomers, mixtures of enantiomers, e.g., racemates, optically pure diastereoisomers, mixtures of diastereoisomers, diastereomeric racemates or mixtures of diastereomeric racemates. In a preferred embodiment, the compounds of formula (I) according to the present invention are cis-enantiomers of formula (Ia) or (Ib), respectively, as described herein.

[0045] According to the Cahn-Ingold-Prelog rules, the asymmetric carbon atom can be of the "R" or "S" configuration.

[0046] The abbreviation "MAGL" refers to the enzyme monoacylglycerol lipase. The terms "MAGL" and "monoacylglycerol lipase" are used interchangeably herein.

[0047] The term "treatment" as used herein includes (1) suppressing a condition, disorder, or symptom (e.g., arresting, reducing, or delaying the onset of a disease or, in the case of maintenance treatment, the recurrence of a disease, the onset of at least one clinical or subclinical symptom of a disease); and / or (2) alleviating symptoms (i.e., causing regression of a condition, disorder, or symptom, or at least one of its clinical or subclinical symptoms). The benefit to the patient to be treated is either statistically significant or at least perceptible to the patient or physician. However, it will be understood that when a pharmaceutical agent is administered to a patient to treat a disease, the result may not necessarily be effective treatment.

[0048] The term "prophylaxis" as used herein includes preventing or delaying the appearance of clinical symptoms of a condition, disorder or condition in a mammal, particularly a human, who may be affected by or predisposed to the condition, disorder or condition, but who has not yet experienced or exhibited clinical or subclinical symptoms of the condition, disorder or condition.

[0049] The term "neuroinflammation," as used herein, refers to acute and chronic inflammation of nervous tissue, which is a major tissue component of two parts of the nervous system: the brain and spinal cord of the central nervous system (CNS), and the branching peripheral nerves of the peripheral nervous system (PNS). Chronic neuroinflammation is associated with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Acute neuroinflammation usually occurs immediately after central nervous system injury, for example, as a result of traumatic brain injury (TBI).

[0050] The term "traumatic brain injury" (also known as "TBI," "intracranial injury") relates to damage to the brain resulting from an external mechanical force such as rapid acceleration or deceleration, impact, blast wave, or penetration by a projectile.

[0051] The term "neurodegenerative disease" refers to diseases associated with the progressive loss of neuronal structure or function, including neuronal death. Examples of neurodegenerative diseases include, but are not limited to, multiple sclerosis, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.

[0052] The term "mental disorder" (also called mental illness or mental disorder) relates to a behavioral or mental pattern that can cause distress or impaired functioning in life. Such characteristics may occur as persistent, relapsing, and remitting, or as a single episode. Examples of mental disorders include, but are not limited to, anxiety and depression.

[0053] The term "pain" relates to an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Examples of pain include, but are not limited to, nociceptive pain, chronic pain (including idiopathic pain), neuropathic pain including chemotherapy-induced neuropathy, phantom limb pain, and psychogenic pain. A particular example of pain is neuropathic pain, which is caused by injury or disease affecting any part of the nervous system involved in bodily sensations (i.e., the somatosensory system). In one embodiment, the "pain" is neuropathic pain resulting from amputation or thoracotomy. In one embodiment, the "pain" is chemotherapy-induced neuropathy.

[0054] The term "neurotoxicity" relates to toxicity in the nervous system. It occurs when exposure to natural or man-made toxic substances (neurotoxins) alters the normal activity of the nervous system, causing damage to nervous tissue. Examples of neurotoxicity include, but are not limited to, exposure to substances used in chemotherapy, radiation treatment, drug therapy, drug abuse, and organ transplants, as well as neurotoxicity resulting from exposure to heavy metals, certain foods and food additives, pesticides, industrial and / or cleaning solvents, cosmetics, and some naturally occurring substances.

[0055] The term "cancer" refers to a disease characterized by the presence of a neoplasm or tumor, resulting from the abnormal and uncontrolled growth of cells (such cells are "cancer cells"). As used herein, the term cancer expressly includes, but is not limited to, hepatocellular carcinoma, colon carcinoma, and ovarian cancer.

[0056] The term "mammal," as used herein, includes both humans and non-humans, including, but not limited to, humans, non-human primates, canines, felines, murines, bovines, equines, and porcines. In a particularly preferred embodiment, the term "mammal" refers to humans.

[0057] Compounds of the Invention In a first aspect, the present invention provides a compound of formula (I) [ka] or a pharmaceutically acceptable salt thereof, wherein: R 5 is the base [ka] , C 1-6 -Alkyl, C 1-6 -Alkoxy, Halo-C 1-6 -Alkyl, Halo-C 1-6 -alkoxy, C 1-6 -Alkyl-SO2-, C 1-6 -alkyl-SO2NH-; R 1 is hydrogen, halogen, SF5, radical [ka] , sulfamoyl, (C 1-6 -alkyl)2PO-C 1-6 -alkyl-, group [ka] , Cyano, C 1-6 -Alkyl, C 1-6 -Alkoxy, Halo-C 1-6 -Alkyl, Halo-C 1-6 -alkoxy, carbamoyl, oxo, C 1-6 -Alkyl-NHC(O)-, C 1-6 -alkoxycarbonyl and C 1-6 -Alkoxycarbonyl-C 1-6 -Alkyl-;C 3-10 -cycloalkyl; and R 2 is hydrogen, halogen, cyano, C 1-6 -Alkyl, C 1-6 -Alkoxy, Halo-C 1-6 -Alkyl, Halo-C 1-6 -alkoxy, and C 1-6-alkylsulfonyl; or R 1 and R 2 together with the atom(s) to which they are attached form one or more C 1-6 - forming a 3- to 14-membered heterocyclic ring optionally substituted with alkyl substituents; R 2a is selected from hydrogen and halogen; R 3 is hydrogen and C 1-6 - selected from alkyl; R 4 is a hydrogen, hydroxy, amino, or [ka] , base [ka] , sulfamoyl, carboxy, hydroxy-C 1-6 -Alkyl, C 1-6 -Alkyl-SO2NH-, Carbamoyl, C 1-6 -alkyl-NHC(O)-, (C 1-6 -alkyl)NC(O)-, C 1-6 -alkyl-C(O)NH-, C 1-6 -alkoxy-C(O)NH- and C 1-6 -alkoxy-C(O)-; R 4a is hydrogen and C 1-6 - selected from alkyl; R 6 is hydrogen, C 6-14 -aryl and halo-C 6-14 - selected from aryl; R 7 is C 1-6 -Alkyl, Cyano-C 1-6 -Alkyl, and halo-C 1-6 - selected from alkyl; R 8 is hydrogen, halogen, cyano, hydroxy, oxo, carboxy, C 1-6-alkoxycarbonyl, C 1-6 -alkyl, group [ka] , base [ka] , base [ka] , C 1-6 -Alkyl-SO-, C 1-6 -Alkyl-S-, C 1-6 -Alkyl-SO2-C 1-6 -alkyl-, (C 1-6 -alkyl)2-PO-, C 1-6 -Alkoxy, Halo-C 1-6 -Alkyl, Halo-C 1-6 -alkoxy, carbamoyl, and C 1-6 -alkyl-NHC(O)-; R 9 is hydrogen, halogen, hydroxy, C 1-6 -Alkyl and halo-C 1-6 - selected from alkyl; R 10 is selected from hydrogen and halogen; R 11 is selected from hydrogen, methyl, cyclopropylmethyl and phenyl; R 12 is hydrogen, halogen, oxo, C 1-6 -Alkyl, C 1-6 -alkoxycarbonyl, and C 3-10 -cycloalkyl; R 13 is hydrogen, C 1-6 -Alkyl and halo-C 1-6 - selected from alkyl; A is C 6-14 -aryl, C 3-10- selected from cycloalkyl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl; B is selected from azetidinyl, piperidyl, piperazinyl, 2-azaspiro[3.3]heptanyl, 2,6-diazaspiro[3.3]heptanyl, 2-azaspiro[3.4]octanyl, 6-azaspiro[3.4]octanyl, 2,7-diazaspiro[3.4]octanyl, 8-azabicyclo[3.2.1]octanyl, 2,7-diazaspiro[3.5]nonanyl, 2-azaspiro[3.5]nonanyl, 7-azaspiro[3.5]nonanyl, 1,2,3,3a,4,5,6,6a-octahydrocyclopenta[c]pyrrolyl, cyclobutyl, cubanyl, bicyclo[1.1.1]pentanyl, and spiro[3.3]heptanyl; C is selected from phenyl, azetidinyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, 4,5-dihydroisoxazolyl, 2-azabicyclo[2.1.1]hexanyl, 2-azaspiro[3.3]heptanyl, and 2,8-diazaspiro[3.5]nonanyl; D is C 6-14 -aryl, C 3-10 - selected from cycloalkyl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl; E is 5- to 14-membered heteroaryl, 3- to 14-membered heterocyclyl, and C 3-10 -cycloalkyl; F is C 3-10 - selected from cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 14-membered heteroaryl; L is a covalent bond, carbonyl, -CHR 6 -, -O-, -NR 11 -, -NHCH2-, -CH2NR 11 -, -N(CH3)CH2-, -OCH2-, -CH2O-, -CH2OCH2-, -CH2CH2-, -CF2CH2-, -CH2CF2-, -CH=CH-, -C≡C-, -SO2-, -SO2NH-, -SO2NHCH2-, -C(O)NH-, -NHC(O)-, -CH2NHC(O)-, and [ka] Selected from; L 1 represents a covalent bond, carbonyl, -CH2-, -CH2O-, -OCH2-, -NHCH2-, CH2NH-, -NR 11 -, -C(O)-NH-NH-C(O)-CH2-, -SO2-, and -O-; L 2 is selected from a covalent bond and -SO2-; L 3 is selected from a covalent bond, a carbonyl, and —CH—; and X is selected from O and NH.

[0058] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: R 5 is the base [ka] , C 1-6 -Alkyl, C 1-6 -Alkoxy, Halo-C 1-6 -Alkyl, Halo-C 1-6 -alkoxy, C 1-6 -Alkyl-SO2-, C 1-6 -alkyl-SO2NH-; R 1 is hydrogen, halogen, SF5, radical [ka] , sulfamoyl, (C 1-6 -alkyl)2PO-C 1-6 -alkyl-, group [ka] , Cyano, C 1-6 -Alkyl, C 1-6 -Alkoxy, Halo-C 1-6 -Alkyl, Halo-C1-6 -alkoxy, carbamoyl, oxo, C 1-6 -Alkyl-NHC(O)-, C 1-6 -alkoxycarbonyl and C 1-6 -Alkoxycarbonyl-C 1-6 -Alkyl-;C 3-10 -cycloalkyl; and R 2 is hydrogen, halogen, cyano, C 1-6 -Alkyl, C 1-6 -Alkoxy, Halo-C 1-6 -Alkyl, Halo-C 1-6 -alkoxy, and C 1-6 -alkylsulfonyl; or R 1 and R 2 together with the atom(s) to which they are attached form one or more C 1-6 - forming a 3- to 14-membered heterocyclic ring optionally substituted with alkyl substituents; R 2a is selected from hydrogen and halogen; R 3 is hydrogen and C 1-6 - selected from alkyl; R 4 is a hydrogen, hydroxy, amino, or [ka] , base [ka] , sulfamoyl, carboxy, hydroxy-C 1-6 -Alkyl, C 1-6 -Alkyl-SO2NH-, Carbamoyl, C 1-6 -alkyl-NHC(O)-, (C 1-6 -alkyl)NC(O)-, C 1-6 -alkyl-C(O)NH-, C 1-6 -alkoxy-C(O)NH- and C 1-6 -alkoxy-C(O)-; R 4a is hydrogen and C 1-6 - selected from alkyl; R 6 is hydrogen, C 6-14 -aryl and halo-C 6-14 - selected from aryl; R 7 is C 1-6 -Alkyl, Cyano-C 1-6 -Alkyl, and halo-C 1-6 - selected from alkyl; R 8 is hydrogen, halogen, cyano, hydroxy, oxo, carboxy, C 1-6 -alkoxycarbonyl, C 1-6 -alkyl, group [ka] , base [ka]

[0059] , base [ka] , C 1-6 -Alkyl-SO-, C 1-6 -Alkyl-S-, C 1-6 -Alkyl-SO2-C 1-6 -alkyl-, (C 1-6 -alkyl)2-PO-, C 1-6 -Alkoxy, Halo-C 1-6 -Alkyl, Halo-C 1-6 -alkoxy, carbamoyl, and C 1-6 -alkyl-NHC(O)-; R 9 is hydrogen, halogen, hydroxy, C 1-6 -Alkyl and halo-C 1-6 - selected from alkyl; R 10 is selected from hydrogen and halogen; R11 is selected from hydrogen, methyl, cyclopropylmethyl and phenyl; R 12 is hydrogen, halogen, oxo, C 1-6 -Alkyl, C 1-6 -alkoxycarbonyl, and C 3-10 -cycloalkyl; R 13 is hydrogen, C 1-6 -Alkyl and halo-C 1-6 - selected from alkyl; A is C 6-14 -aryl, C 3-10 - selected from cycloalkyl, 5- to 6-membered heteroaryl, and 3- to 14-membered heterocyclyl; B can be azetidinyl, piperidyl, piperazinyl, 2-azaspiro[3.3]heptanyl, 2,6-diazaspiro[3.3]heptanyl, 2-azaspiro[3.4]octanyl, 6-azaspiro[3.4]octanyl, 2,7-diazaspiro[3.4]octanyl, 2,7-diazaspiro[3.5]nonanyl, 2-azaspiro[3.5]nonanyl, 7-azaspiro[3.5]nonanyl, 1,2,3,3a,4,5,6,6a-octahydrocyclopenta[c]pyrrolyl, cyclobutyl, cubanyl, spiro[3.3]heptanyl, or a group [ka] and groups [ka] Selected from; C is selected from phenyl, azetidinyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, 4,5-dihydroisoxazolyl, 2-azabicyclo[2.1.1]hexanyl, 2-azaspiro[3.3]heptanyl, and 2,8-diazaspiro[3.5]nonanyl; D is C 6-14 -aryl, C 3-10 - selected from cycloalkyl, 5- to 6-membered heteroaryl, and 3- to 14-membered heterocyclyl; E is 5- to 14-membered heteroaryl, 3- to 14-membered heterocyclyl, and C 3-10 -cycloalkyl; F is C 3-10 - selected from cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 14-membered heteroaryl; L is a covalent bond, carbonyl, -CHR 6 -, -O-, -NR 11 -, -NHCH2-, -CH2NR 11 -, -N(CH3)CH2-, -OCH2-, -CH2O-, -CH2OCH2-, -CH2CH2-, -CF2CH2-, -CH2CF2-, -CH=CH-, -C≡C-, -SO2-, -SO2NH-, -SO2NHCH2-, -C(O)NH-, -NHC(O)-, -CH2NHC(O)-, and [ka] Selected from; L 1 represents a covalent bond, carbonyl, -CH2-, -CH2O-, -OCH2-, -NHCH2-, CH2NH-, -NR 11 -, -C(O)-NH-NH-C(O)-CH2-, -SO2-, and -O-; L 2 is selected from a covalent bond and -SO2-; L 3 is selected from a covalent bond, a carbonyl, and -CH2-; X is selected from O and NH; However, when B is 2-azaspiro[3.3]heptanyl or 2,6-diazaspiro[3.3]heptanyl, L is not a covalent bond.

[0060] 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 a compound of formula (II) [ka] where R 1 ~R 4 , R 2a , R 4a , A, B and L are as defined herein; and p and q are each independently selected from 0 and 1.

[0061] 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 a compound of formula (I-II) [ka] where R 1 ~R 4 , R 2a , R 4a , A, B and L are as defined herein.

[0062] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: R 5 is the base [ka] , C 1-6 -Alkyl-SO2-, C 1-6 -Alkyl-SO2NH-, and halo-C 1-6 - selected from alkoxy; R 1 is hydrogen, halogen, SF5, radical [ka] , sulfamoyl, (C 1-6 -alkyl)2PO-C 1-6 -alkyl-, group [ka] , C 1-6 -Alkyl, C1-6 -Alkoxy, Halo-C 1-6 -Alkyl, Halo-C 1-6 -alkoxy, carbamoyl, oxo, C 1-6 -Alkyl-NHC(O)-, C 1-6 -alkoxycarbonyl, and C 1-6 -Alkoxycarbonyl-C 1-6 -alkyl-; and R 2 is hydrogen, halogen, cyano, C 1-6 -Alkyl, C 1-6 -Alkoxy, Halo-C 1-6 -Alkyl, Halo-C 1-6 -alkoxy, and C 1-6 -alkylsulfonyl; or R 1 and R 2 together with the atom(s) to which they are attached, form one or two C 1-6 - forming a 3- to 14-membered heterocyclic ring optionally substituted with alkyl substituents; R 2a is selected from hydrogen and halogen; R 6 is hydrogen, C 6-14 -aryl and halo-C 6-14 - selected from aryl; R 7 is C 1-6 -Alkyl, Cyano-C 1-6 -Alkyl, and halo-C 1-6 - selected from alkyl; R 8 is hydrogen, halogen, cyano, hydroxy, oxo, carboxy, C 1-6 -alkoxycarbonyl, C 1-6 -alkyl, group [ka] , base [ka] , base [ka] , C 1-6 -Alkyl-SO-, C 1-6 -Alkyl-S-, C 1-6 -Alkyl-SO2-C 1-6 -alkyl-, (C 1-6 -alkyl)2-PO-, C 1-6 -Alkoxy, Halo-C 1-6 -Alkyl, Halo-C 1-6 -alkoxy, carbamoyl, and C 1-6 -alkyl-NHC(O)-; R 9 is hydrogen, halogen, hydroxy, C 1-6 -Alkyl and halo-C 1-6 - selected from alkyl; R 10 is selected from hydrogen and halogen; R 11 is selected from hydrogen, methyl, cyclopropylmethyl and phenyl; R 13 is hydrogen, C 1-6 -Alkyl and halo-C 1-6 - selected from alkyl; A is C 6-14 -aryl, C 3-10 - selected from cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 14-membered heteroaryl; D is C 6-14 -aryl, C 3-10 - selected from cycloalkyl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl; F is C 3-10 - selected from cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 14-membered heteroaryl; L is a covalent bond, -CHR 6 -, -O-, -NR 11 -, -NHCH2-, -CH2NR 11-, -OCH2-, -CH2O-, -CH2OCH2-, -CH2CH2-, -CF2CH2-, -CH2CF2-, -CH=CH-, -C≡C-, -SO2-, -SO2NH-, -SO2NHCH2-, -C(O)NH-, -NHC(O)-, -CH2NHC(O)-, and [ka] Selected from; L 1 represents a covalent bond, carbonyl, -CH2-, -CH2O-, -NHCH2-, CH2NH-, -NR 11 -, -C(O)-NH-NH-C(O)-CH2-, -SO2-, and -O-; L 3 is selected from a covalent bond, a carbonyl, and —CH—; and X is selected from O and NH.

[0063] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: R 5 is the base [ka] , C 1-6 -Alkyl-SO2-, C 1-6 -Alkyl-SO2NH-, and halo-C 1-6 - selected from alkoxy; R 1 is hydrogen, halogen, SF5, radical [ka] , sulfamoyl, (C 1-6 -alkyl)2PO-C 1-6 -alkyl-, group [ka] , C 1-6 -Alkyl, C1-6 -Alkoxy, Halo-C 1-6 -Alkyl, Halo-C 1-6 -alkoxy, carbamoyl, oxo, C 1-6 -Alkyl-NHC(O)-, C 1-6 -alkoxycarbonyl, and C 1-6 -Alkoxycarbonyl-C 1-6 -alkyl-; and R 2 is hydrogen, halogen, cyano, C 1-6 -Alkyl, C 1-6 -Alkoxy, Halo-C 1-6 -Alkyl, Halo-C 1-6 -alkoxy, and C 1-6 -alkylsulfonyl; or R 1 and R 2 together with the atom(s) to which they are attached, form one or two C 1-6 - forming a 3- to 14-membered heterocyclic ring optionally substituted with alkyl substituents; R 2a is selected from hydrogen and halogen; R 6 is hydrogen, C 6-14 -aryl and halo-C 6-14 - selected from aryl; R 7 is C 1-6 -Alkyl, Cyano-C 1-6 -Alkyl, and halo-C 1-6 - selected from alkyl; R 8 is hydrogen, halogen, cyano, hydroxy, oxo, carboxy, C 1-6 -alkoxycarbonyl, C 1-6 -alkyl, group [ka] , base [ka] , base [ka] , C 1-6 -Alkyl-SO-, C 1-6 -Alkyl-S-, C 1-6 -Alkyl-SO2-C 1-6 -alkyl-, (C 1-6 -alkyl)2-PO-, C 1-6 -Alkoxy, Halo-C 1-6 -Alkyl, Halo-C 1-6 -alkoxy, carbamoyl, and C 1-6 -alkyl-NHC(O)-; R 9 is hydrogen, halogen, hydroxy, C 1-6 -Alkyl and halo-C 1-6 - selected from alkyl; R 10 is selected from hydrogen and halogen; R 11 is selected from hydrogen, methyl, cyclopropylmethyl and phenyl; R 13 is hydrogen, C 1-6 -Alkyl and halo-C 1-6 - selected from alkyl; A is C 6-14 -aryl, C 3-10 - selected from cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 6-membered heteroaryl; D is C 6-14 -aryl, C 3-10 - selected from cycloalkyl, 5- to 6-membered heteroaryl, and 3- to 14-membered heterocyclyl; F is C 3-10 - selected from cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 14-membered heteroaryl; L is a covalent bond, -CHR 6 -, -O-, -NR 11 -, -NHCH2-, -CH2NR 11-, -OCH2-, -CH2O-, -CH2OCH2-, -CH2CH2-, -CF2CH2-, -CH2CF2-, -CH=CH-, -C≡C-, -SO2-, -SO2NH-, -SO2NHCH2-, -C(O)NH-, -NHC(O)-, -CH2NHC(O)-, and [ka] Selected from; L 1 represents a covalent bond, carbonyl, -CH2-, -CH2O-, -NHCH2-, CH2NH-, -NR 11 -, -C(O)-NH-NH-C(O)-CH2-, -SO2-, and -O-; L 3 is selected from a covalent bond, a carbonyl, and —CH—; and X is selected from O and NH.

[0064] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: R 5 is the base [ka] and; R 1 is a halogen, C 1-6 -Alkyl, Halo-C 1-6 -alkyl, and groups [ka] Selected from; R 2 are hydrogen, halogens and halo-C 1-6 - selected from alkyl; R 2a is hydrogen; R 8 and R 9 are each independently halogen and halo-C 1-6 - selected from alkyl; R 10 is hydrogen; A is C 6-14 -aryl and C 3-10 -cycloalkyl; D is C 6-14 -aryl and C 3-10 -cycloalkyl; L is selected from a covalent bond, —O—, and —CHO—; and L 1 is a covalent bond.

[0065] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: R 5 is the base [ka] and; R 1 is fluoro, chloro, tert-butyl, CHF2, CF3, and the group [ka] Selected from; R 2 is selected from hydrogen, fluoro, chloro and CF3; R 2a is hydrogen; R 8 and R 9 are each independently selected from fluoro, chloro, and CF3; R 10 is hydrogen; A is selected from phenyl and cyclopropyl; D is selected from phenyl and cyclopropyl; L is selected from a covalent bond, —O—, and —CHO—; and L 1 is a covalent bond.

[0066] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: B is selected from spiro[3.3]heptan-2-yl, azetidinyl, and 7-azaspiro[3.5]nonan-7-yl; and R 3 is hydrogen.

[0067] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: R 4 is the base [ka] and carbamoyl; R 4a is hydrogen; R 12 is selected from hydrogen and oxo; C is pyrrolidinyl; E is selected from 5-membered heteroaryl and 5-membered heterocyclyl; and L 2 is a covalent bond.

[0068] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: R 4 is the base [ka] and carbamoyl; R 4a is hydrogen; R 12 is selected from hydrogen and oxo; C is pyrrolidinyl; E is selected from imidazolyl, pyrazolyl, triazolyl, and oxazolidinyl; and L 2 is a covalent bond.

[0069] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: R 5 is the base [ka] , C 1-6 -Alkyl-SO2-, C 1-6 -Alkyl-SO2NH-, and halo-C 1-6 - selected from alkoxy; R 1 is hydrogen, halogen, SF5, radical [ka] , sulfamoyl, (C 1-6 -alkyl)2PO-C 1-6 -alkyl-, group [ka] , C 1-6 -Alkyl, C 1-6 -Alkoxy, Halo-C 1-6 -Alkyl, Halo-C 1-6 -alkoxy, carbamoyl, oxo, C 1-6 -Alkyl-NHC(O)-, C 1-6 -alkoxycarbonyl, and C 1-6 -Alkoxycarbonyl-C 1-6 -alkyl-; and R 2 is hydrogen, halogen, cyano, C 1-6 -Alkyl, C 1-6 -Alkoxy, Halo-C 1-6 -Alkyl, Halo-C 1-6 -alkoxy, and C 1-6 -alkylsulfonyl; or R 1 and R 2together with the atom(s) to which they are attached, form one or two C 1-6 - forming a 3- to 14-membered heterocyclic ring optionally substituted with alkyl substituents; R 2a is selected from hydrogen and halogen; R 3 is hydrogen and C 1-6 - selected from alkyl; R 4 is a hydrogen, hydroxy, amino, or [ka] , base [ka] , sulfamoyl, carboxy, hydroxy-C 1-6 -Alkyl, C 1-6 -Alkyl-SO2NH-, Carbamoyl, C 1-6 -alkyl-NHC(O)-, (C 1-6 -alkyl)NC(O)-, C 1-6 -alkyl-C(O)NH-, C 1-6 -alkoxy-C(O)NH- and C 1-6 -alkoxy-C(O)-; R 4a is hydrogen and C 1-6 - selected from alkyl; R 6 is hydrogen, C 6-14 -aryl and halo-C 6-14 - selected from aryl; R 7 is C 1-6 -Alkyl, Cyano-C 1-6 -Alkyl, and halo-C 1-6 - selected from alkyl; R 8 is hydrogen, halogen, cyano, hydroxy, oxo, carboxy, C 1-6 -alkoxycarbonyl, C 1-6 -alkyl, group [ka] , base [ka] , base [ka] , C 1-6 -Alkyl-SO-, C 1-6 -Alkyl-S-, C 1-6 -Alkyl-SO2-C 1-6 -alkyl-, (C 1-6 -alkyl)2-PO-, C 1-6 -Alkoxy, Halo-C 1-6 -Alkyl, Halo-C 1-6 -alkoxy, carbamoyl, and C 1-6 -alkyl-NHC(O)-; R 9 is hydrogen, halogen, hydroxy, C 1-6 -Alkyl and halo-C 1-6 - selected from alkyl; R 10 is selected from hydrogen and halogen; R 11 is selected from hydrogen, methyl, cyclopropylmethyl and phenyl; R 12 is hydrogen, halogen, oxo, C 1-6 -Alkyl, C 1-6 -alkoxycarbonyl, and C 3-10 -cycloalkyl; R 13 is hydrogen, C 1-6 -Alkyl and halo-C 1-6 - selected from alkyl; A is C 6-14 -aryl, C 3-10 - selected from cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 14-membered heteroaryl; B is selected from azetidinyl, piperidyl, piperazinyl, 2-azaspiro[3.3]heptanyl, 2,6-diazaspiro[3.3]heptanyl, 2-azaspiro[3.4]octanyl, 6-azaspiro[3.4]octanyl, 2,7-diazaspiro[3.4]octanyl, 8-azabicyclo[3.2.1]octanyl, 2,7-diazaspiro[3.5]nonanyl, 2-azaspiro[3.5]nonanyl, 7-azaspiro[3.5]nonanyl, 1,2,3,3a,4,5,6,6a-octahydrocyclopenta[c]pyrrolyl, cyclobutyl, cubanyl, bicyclo[1.1.1]pentanyl, and spiro[3.3]heptanyl; C is selected from phenyl, azetidinyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, 4,5-dihydroisoxazolyl, 2-azabicyclo[2.1.1]hexanyl, 2-azaspiro[3.3]heptanyl, and 2,8-diazaspiro[3.5]nonanyl; D is C 6-14 -aryl, C 3-10 - selected from cycloalkyl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl; E is 5- to 14-membered heteroaryl, 3- to 14-membered heterocyclyl, and C 3-10 -cycloalkyl; F is C 3-10 - selected from cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 14-membered heteroaryl; L is a covalent bond, -CHR 6 -, -O-, -NR 11 -, -NHCH2-, -CH2NR 11 -, -OCH2-, -CH2O-, -CH2OCH2-, -CH2CH2-, -CF2CH2-, -CH2CF2-, -CH=CH-, -C≡C-, -SO2-, -SO2NH-, -SO2NHCH2-, -C(O)NH-, -NHC(O)-, -CH2NHC(O)-, and [ka] Selected from; L 1represents a covalent bond, carbonyl, -CH2-, -CH2O-, -NHCH2-, CH2NH-, -NR 11 -, -C(O)-NH-NH-C(O)-CH2-, -SO2-, and -O-; L 2 is selected from a covalent bond and -SO2-; L 3 is selected from a covalent bond, a carbonyl, and —CH—; and X is selected from O and NH.

[0070] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: R 5 is the base [ka] , C 1-6 -Alkyl-SO2-, C 1-6 -Alkyl-SO2NH-, and halo-C 1-6 - selected from alkoxy; R 1 is hydrogen, halogen, SF5, radical [ka] , sulfamoyl, (C 1-6 -alkyl)2PO-C 1-6 -alkyl-, group [ka] , C 1-6 -Alkyl, C 1-6 -Alkoxy, Halo-C 1-6 -Alkyl, Halo-C 1-6 -alkoxy, carbamoyl, oxo, C 1-6 -Alkyl-NHC(O)-, C 1-6 -alkoxycarbonyl, and C 1-6 -Alkoxycarbonyl-C 1-6 -alkyl-; and R 2 is hydrogen, halogen, cyano, C 1-6 -Alkyl, C 1-6 -Alkoxy, Halo-C 1-6 -Alkyl, Halo-C 1-6 -alkoxy, and C 1-6 -alkylsulfonyl; or R 1 and R 2 together with the atom(s) to which they are attached, form one or two C 1-6 - forming a 3- to 14-membered heterocyclic ring optionally substituted with alkyl substituents; R 2a is selected from hydrogen and halogen; R 3 is hydrogen and C 1-6 - selected from alkyl; R 4 is a hydrogen, hydroxy, amino, or [ka] , base [ka] , sulfamoyl, carboxy, hydroxy-C 1-6 -Alkyl, C 1-6 -Alkyl-SO2NH-, Carbamoyl, C 1-6 -alkyl-NHC(O)-, (C 1-6 -alkyl)NC(O)-, C 1-6 -alkyl-C(O)NH-, C 1-6 -alkoxy-C(O)NH- and C 1-6 -alkoxy-C(O)-; R 4a is hydrogen and C 1-6 - selected from alkyl; R 6 is hydrogen, C 6-14 -aryl and halo-C 6-14 - selected from aryl; R 7 is C1-6 -Alkyl, Cyano-C 1-6 -Alkyl, and halo-C 1-6 - selected from alkyl; R 8 is hydrogen, halogen, cyano, hydroxy, oxo, carboxy, C 1-6 -alkoxycarbonyl, C 1-6 -alkyl, group [ka] , base [ka] , base [ka]

[0071] , C 1-6 -Alkyl-SO-, C 1-6 -Alkyl-S-, C 1-6 -Alkyl-SO2-C 1-6 -alkyl-, (C 1-6 -alkyl)2-PO-, C 1-6 -Alkoxy, Halo-C 1-6 -Alkyl, Halo-C 1-6 -alkoxy, carbamoyl, and C 1-6 -alkyl-NHC(O)-; R 9 is hydrogen, halogen, hydroxy, C 1-6 -Alkyl and halo-C 1-6 - selected from alkyl; R 10 is selected from hydrogen and halogen; R 11 is selected from hydrogen, methyl, cyclopropylmethyl and phenyl; R 12 is hydrogen, halogen, oxo, C 1-6 -Alkyl, C 1-6 -alkoxycarbonyl, and C 3-10 -cycloalkyl; R 13 is hydrogen, C 1-6 -Alkyl and halo-C 1-6 - selected from alkyl; A is C 6-14 -aryl, C 3-10 - selected from cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 6-membered heteroaryl; B can be azetidinyl, piperidyl, piperazinyl, 2-azaspiro[3.3]heptanyl, 2,6-diazaspiro[3.3]heptanyl, 2-azaspiro[3.4]octanyl, 6-azaspiro[3.4]octanyl, 2,7-diazaspiro[3.4]octanyl, 2,7-diazaspiro[3.5]nonanyl, 2-azaspiro[3.5]nonanyl, 7-azaspiro[3.5]nonanyl, 1,2,3,3a,4,5,6,6a-octahydrocyclopenta[c]pyrrolyl, cyclobutyl, cubanyl, spiro[3.3]heptanyl, or a group [ka] and groups [ka] Selected from; C is selected from phenyl, azetidinyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, 4,5-dihydroisoxazolyl, 2-azabicyclo[2.1.1]hexanyl, 2-azaspiro[3.3]heptanyl, and 2,8-diazaspiro[3.5]nonanyl; D is C 6-14 -aryl, C 3-10 - selected from cycloalkyl, 5- to 6-membered heteroaryl, and 3- to 14-membered heterocyclyl; E is 5- to 14-membered heteroaryl, 3- to 14-membered heterocyclyl, and C 3-10 -cycloalkyl; F is C 3-10 - selected from cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 14-membered heteroaryl; L is a covalent bond, -CHR 6 -, -O-, -NR 11 -, -NHCH2-, -CH2NR 11 -, -OCH2-, -CH2O-, -CH2OCH2-, -CH2CH2-, -CF2CH2-, -CH2CF2-, -CH=CH-, -C≡C-, -SO2-, -SO2NH-, -SO2NHCH2-, -C(O)NH-, -NHC(O)-, -CH2NHC(O)-, and [ka] Selected from; L 1 represents a covalent bond, carbonyl, -CH2-, -CH2O-, -NHCH2-, CH2NH-, -NR 11 -, -C(O)-NH-NH-C(O)-CH2-, -SO2-, and -O-; L 2 is selected from a covalent bond and -SO2-; L 3 is selected from a covalent bond, a carbonyl, and —CH—; and X is selected from O and NH.

[0072] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: R 5 is the base [ka] and; R 1 is a halogen, C 1-6 -Alkyl, Halo-C 1-6 -alkyl, and groups [ka] Selected from; R 2 are hydrogen, halogens and halo-C 1-6 - selected from alkyl; R 2a is hydrogen; R 3 is hydrogen; R 4 is the base [ka] and carbamoyl; R 4a is hydrogen; R 8 and R 9 are each independently halogen and halo-C 1-6 - selected from alkyl; R 10 is hydrogen; R 12 is selected from hydrogen and oxo; A is C 6-14 -aryl and C 3-10 -cycloalkyl; B is selected from spiro[3.3]heptan-2-yl, azetidinyl, and 7-azaspiro[3.5]nonan-7-yl; C is pyrrolidinyl; D is C 6-14 -aryl and C 3-10 -cycloalkyl; E is selected from 5-membered heteroaryl and 5-membered heterocyclyl; L is selected from a covalent bond, —O—, and —CHO—; L 1 is a covalent bond; and L 2 is a covalent bond.

[0073] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein: R 5 is the base [ka] and; R 1 is fluoro, chloro, tert-butyl, CHF2, CF3, and the group [ka] Selected from; R 2 is selected from hydrogen, fluoro, chloro and CF3; R 2a is hydrogen; R 3 is hydrogen; R 4 is the base [ka] and carbamoyl; R 4a is hydrogen; R 8 and R 9 are each independently selected from fluoro, chloro, and CF3; R 10 is hydrogen; R 12 is selected from hydrogen and oxo; A is selected from phenyl and cyclopropyl; B is selected from spiro[3.3]heptan-2-yl, azetidinyl, and 7-azaspiro[3.5]nonan-7-yl; C is pyrrolidinyl; D is selected from phenyl and cyclopropyl; E is selected from imidazolyl, pyrazolyl, triazolyl, and oxazolidinyl; L is selected from a covalent bond, —O—, and —CHO—; L 1 is a covalent bond; and L 2 is a covalent bond.

[0074] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R 5 is the base [ka] , C 1-6 -Alkyl-SO2-, C 1-6 -Alkyl-SO2NH-, and halo-C 1-6 -alkoxy; R 1 , R 2 , A and L are as described herein.

[0075] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen, halogen, SF5, radical [ka] , sulfamoyl, (C 1-6 -alkyl)2PO-C 1-6 -alkyl-, group [ka] , C 1-6 -Alkyl, C 1-6 -Alkoxy, Halo-C 1-6 -Alkyl, Halo-C 1-6 -alkoxy, carbamoyl, oxo, C 1-6 -Alkyl-NHC(O)-, C 1-6 -alkoxycarbonyl and C 1-6 -Alkoxycarbonyl-C 1-6 -alkyl-; wherein R 7 ~R 10 , X, D and L 1 is as defined herein.

[0076] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 together with the atom(s) to which they are attached form one or more C 1-6 -Forms a 3- to 14-membered heterocyclic ring optionally substituted with alkyl substituents.

[0077] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein L is a covalent bond, -CHR 6 -, -O-, -NR 11 -, -NHCH2-, -CH2NR 11 -, -OCH2-, -CH2O-, -CH2OCH2-, -CH2CH2-, -CF2CH2-, -CH2CF2-, -CH=CH-, -C≡C-, -SO2-, -SO2NH-, -SO2NHCH2-, -C(O)NH-, -NHC(O)-, -CH2NHC(O)-, and [ka] wherein R 6 and R 11 is as defined herein.

[0078] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is azetidinyl.

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

[0080] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is piperazinyl.

[0081] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 2-azaspiro[3.3]heptanyl.

[0082] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 2,6-diazaspiro[3.3]heptanyl.

[0083] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 2-azaspiro[3.4]octanyl.

[0084] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 6-azaspiro[3.4]octanyl.

[0085] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 2,7-diazaspiro[3.4]octanyl.

[0086] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 8-azabicyclo[3.2.1]octanyl.

[0087] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 2,7-diazaspiro[3.5]nonanyl.

[0088] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 2-azaspiro[3.5]nonanyl.

[0089] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 7-azaspiro[3.5]nonanyl.

[0090] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 1,2,3,3a,4,5,6,6a-octahydrocyclopenta[c]pyrrolyl.

[0091] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is cyclobutyl.

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

[0093] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is bicyclo[1.1.1]pentanyl.

[0094] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is spiro[3.3]heptanyl.

[0095] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein C is phenyl.

[0096] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein C is azetidinyl.

[0097] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein C is pyrrolidinyl.

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

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

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

[0101] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein C is 4,5-dihydroisoxazolyl.

[0102] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein C is 2-azabicyclo[2.1.1]hexanyl.

[0103] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein C is 2-azaspiro[3.3]heptanyl.

[0104] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein C is 2,8-diazaspiro[3.5]nonanyl.

[0105] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is azetidinyl and C is pyrrolidinyl.

[0106] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 2-azaspiro[3.3]heptanyl and C is pyrrolidinyl.

[0107] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 2,6-diazaspiro[3.3]heptanyl and C is pyrrolidinyl.

[0108] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 2,7-diazaspiro[3.5]nonanyl and C is pyrrolidinyl.

[0109] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 2-azaspiro[3.5]nonanyl and C is pyrrolidinyl.

[0110] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 7-azaspiro[3.5]nonanyl and C is pyrrolidinyl.

[0111] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 2-azaspiro[3.4]octanyl and C is pyrrolidinyl.

[0112] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 2,7-diazaspiro[3.4]octanyl and C is pyrrolidinyl.

[0113] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is piperidyl and C is pyrrolidinyl.

[0114] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B and C are both azetidinyl.

[0115] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 2,7-diazaspiro[3.5]nonanyl and C is azetidinyl.

[0116] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is azetidinyl and C is morpholinyl.

[0117] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is azetidinyl and C is piperidyl.

[0118] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is azetidinyl and C is piperazinyl.

[0119] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 2-azaspiro[3.3]heptanyl and C is piperidyl.

[0120] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is azetidinyl and C is 4,5-dihydroisoxazolyl.

[0121] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 2,7-diazaspiro[3.5]nonanyl and C is piperidyl.

[0122] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 6-azaspiro[3.4]octanyl and C is pyrrolidinyl.

[0123] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is cubanyl and C is pyrrolidinyl.

[0124] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is piperazinyl and C is pyrrolidinyl.

[0125] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is bicyclo[1.1.1]pentanyl and C is pyrrolidinyl.

[0126] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 8-azabicyclo[3.2.1]octanyl and C is pyrrolidinyl.

[0127] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is 1,2,3,3a,4,5,6,6a-octahydrocyclopenta[c]pyrrolyl and C is pyrrolidinyl.

[0128] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is cyclobutyl and C is pyrrolidinyl.

[0129] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is bicyclo[1.1.1]pentanyl and C is pyrrolidinyl.

[0130] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is spiro[3.3]heptanyl and C is pyrrolidinyl.

[0131] In one embodiment, the present invention provides a method for producing a compound comprising: 1 Covalent bond, carbonyl, -CH2-, -CH2O-, -NHCH2-, CH2NH-, -NR 11

[0010] Provided are compounds of formula (I) as described herein, selected from -, -C(O)-NH-NH-C(O)-CH2-, -SO2-, and -O-, or a pharmaceutically acceptable salt thereof.

[0132] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R 5 is the base [ka] where R 1 , R 2 , A and L are as defined herein.

[0133] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R 1 is a halogen, C 1-6 -Alkyl, Halo-C 1-6 -alkyl, and groups [ka] wherein R 8 ~R 10 , D and L 1 is as defined herein.

[0134] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R 2 are hydrogen, halogens, and halo-C 1-6 -alkyl.

[0135] In a preferred embodiment, the present invention provides R 2ais hydrogen, or a pharmaceutically acceptable salt thereof.

[0136] In a preferred embodiment, the present invention provides R 3 is hydrogen, or a pharmaceutically acceptable salt thereof.

[0137] In a preferred embodiment, the present invention provides R 4 Based on [ka] and carbamoyl, or a pharmaceutically acceptable salt thereof.

[0138] In a preferred embodiment, the present invention provides R 4a is hydrogen, or a pharmaceutically acceptable salt thereof.

[0139] In a preferred embodiment, the present invention provides R 8 and R 9 are each independently halogen and halo-C 1-6 -alkyl, or a pharmaceutically acceptable salt thereof.

[0140] In a preferred embodiment, the present invention provides R 10 is hydrogen, or a pharmaceutically acceptable salt thereof.

[0141] In a preferred embodiment, the present invention provides R 12 is selected from hydrogen and oxo, or a pharmaceutically acceptable salt thereof.

[0142] In a preferred embodiment, the present invention provides a method for treating a cancer comprising administering to a patient a cancer-related disorder, ... 6-14 -aryl and C 3-10-cycloalkyl, or a pharmaceutically acceptable salt thereof.

[0143] In a preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein B is selected from spiro[3.3]heptan-2-yl, azetidinyl, and 7-azaspiro[3.5]nonan-7-yl.

[0144] In a preferred embodiment, the present invention provides a method for treating a cancer comprising administering to a patient a cancer-related disorder, ... 6-14 -aryl and C 3-10 -cycloalkyl, or a pharmaceutically acceptable salt thereof.

[0145] In a preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein E is selected from 5-membered heteroaryl and 5-membered heterocyclyl.

[0146] In a preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein L is selected from a covalent bond, —O—, and —CHO—.

[0147] In a preferred embodiment, the present invention provides L 1 is a covalent bond, or a pharmaceutically acceptable salt thereof.

[0148] In a preferred embodiment, the present invention provides L 2 is a covalent bond, or a pharmaceutically acceptable salt thereof.

[0149] In a particularly preferred embodiment, the present invention provides 1 Fluoro, chloro, tert-butyl, CHF2, CF3 and groups [ka] The present invention provides a compound of formula (I) as described herein, selected from:

[0150] In a particularly preferred embodiment, the present invention provides 2 is selected from hydrogen, fluoro, chloro and CF3, or a pharmaceutically acceptable salt thereof.

[0151] In a particularly preferred embodiment, the present invention provides 8 and R 9 are each independently selected from fluoro, chloro and CF3, or a pharmaceutically acceptable salt thereof.

[0152] In a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein A is selected from phenyl and cyclopropyl.

[0153] In a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein A is phenyl.

[0154] In a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein A is cyclopropyl.

[0155] In a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein D is selected from phenyl and cyclopropyl.

[0156] In a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein D is phenyl.

[0157] In a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein D is cyclopropyl.

[0158] In a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein E is selected from imidazolyl, pyrazolyl, triazolyl and oxazolidinyl.

[0159] In a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein E is imidazolyl.

[0160] In a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein E is pyrazolyl.

[0161] In a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein E is triazolyl.

[0162] In a particularly preferred embodiment, the present invention provides compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein E is oxazolidinyl.

[0163] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: [3-[[2-fluoro-6-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; 4-[1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidin-3-yl]oxazolidin-2-one; (+)- or (-)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; (-)- or (+)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(4-methyl-1H-pyrazol-5-yl)azetidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)azetidin-1-yl]methanone; [4-[(2-chloro-4-fluoro-phenyl)methoxy]-1-piperidyl]-[3-(4-methyl-1H-pyrazol-5-yl)azetidin-1-yl]methanone; [4-[(4-chloro-2-fluoro-phenoxy)methyl]-1-piperidyl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)-1-piperidyl]methanone; [6-(2-chloro-4-fluoro-phenoxy)-2-azaspiro[3.3]heptan-2-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; [3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]-[4-[[4-(trifluoromethyl)phenyl]methyl]-1-piperidyl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(2-methylpyrazol-3-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)phenyl]methanone; [3-[[2-fluoro-4-(pentafluoro-λ6-sulfanyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; (+)- or (-)-[3-[[2-fluoro-6-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; (-)- or (+)-[3-[[2-fluoro-6-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-(2,4-dichlorophenyl)phenyl]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; 6-[1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidin-3-yl]-1H-pyridin-2-one; 6-[1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidin-3-yl]-1H-pyrazin-2-one; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(4-isopropyl-1H-pyrazol-3-yl)pyrrolidin-1-yl]methanone; 4-[1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidin-3-yl]oxazolidin-2-one; Ethyl 5-[1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidin-3-yl]-1H-pyrazole-4-carboxylate; 5-[1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidin-3-yl]pyrrolidin-2-one; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3R)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; 1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone; [3-(4-tert-butylphenyl)azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1,2,4-triazol-1-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-(3-imidazol-1-ylpyrrolidin-1-yl)methanone; [3-[[2,4-bis(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (+)- or (-)-[2-(2-chloro-4-fluoro-phenoxy)-7-azaspiro[3.5]nonan-7-yl]-[(3R)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (-)- or (+)-[2-(2-chloro-4-fluoro-phenoxy)-7-azaspiro[3.5]nonan-7-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (+)- or (-)-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]-[3-(4-tetrahydropyran-4-ylphenyl)azetidin-1-yl]methanone; (-)- or (+)-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]-[3-(4-tetrahydropyran-4-ylphenyl)azetidin-1-yl]methanone; (+)- or (-)-[3-(4-isopropoxyphenyl)azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; (-)- or (+)-[3-(4-isopropoxyphenyl)azetidin-1-yl]-[(3S)-3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; (+)- or (-)-[6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (-)- or (+)-[6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-imidazol-5-yl)pyrrolidin-1-yl]methanone; (+)- or (-)-[2-[2-fluoro-4-(trifluoromethyl)phenoxy]-7-azaspiro[3.5]nonan-7-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (-)- or (+)-[2-[2-fluoro-4-(trifluoromethyl)phenoxy]-7-azaspiro[3.5]nonan-7-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-imidazol-2-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; Sodium [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[rac-(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; (+)- or (-)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-imidazol-1-ylpyrrolidin-1-yl]methanone; (-)- or (+)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-imidazol-1-ylpyrrolidin-1-yl]methanone; [3-[[3-chloro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-chloro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (+)- or (-)-[3-[2-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (-)- or (+)-[3-[2-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (+)- or (-)-[3-(4-propoxyphenyl)azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; (-)- or (+)-[3-(4-propoxyphenyl)azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; (+)- or (-)-[3-[[2,4-bis(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (-)- or (+)-[3-[[2,4-bis(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-tetrazol-5-yl)pyrrolidin-1-yl]methanone; (+)- or (-)-1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]-N-methyl-pyrrolidine-3-carboxamide; (-)- or (+)-1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]-N-methyl-pyrrolidine-3-carboxamide; (+)- or (-)-1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]-N,N-dimethyl-pyrrolidine-3-carboxamide; (-)- or (+)-1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]-N,N-dimethyl-pyrrolidine-3-carboxamide; (+)- or (-)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-pyrazol-1-ylpyrrolidin-1-yl]methanone; (-)- or (+)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-pyrazol-1-ylpyrrolidin-1-yl]methanone; (+)- or (-)-1-[3-[4-(2,4-difluorophenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (-)- or (+)-1-[3-[4-(2,4-difluorophenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]-[3-(4-THF-3-ylphenyl)azetidin-1-yl]methanone; [3-(4-tert-butylphenyl)azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; [3-[2-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl]azetidin-1-yl]-[(3S)-3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(triazol-1-yl)pyrrolidin-1-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; [3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]-[3-(4-tetrahydropyran-3-ylphenyl)azetidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-(3-pyrrol-1-ylpyrrolidin-1-yl)methanone; trans-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]cyclobutyl]-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; (+)- or (-)-[3-[4-[(1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl]phenyl]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; (-)- or (+)-[3-[4-[(1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl]phenyl]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; (-)- or (+)-[3-[4-(2,4-difluorophenyl)phenyl]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (+)- or (-)-[3-[4-(2,4-difluorophenyl)phenyl]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-(2,4-difluorophenyl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; [4-[bis(4-fluorophenyl)methyl]-1-piperidyl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; 4-[1-[3-[3-chloro-4-(trifluoromethoxy)phenyl]azetidine-1-carbonyl]pyrrolidin-3-yl]oxazolidin-2-one; [3-[4-(2-methylazetidin-1-yl)phenyl]azetidin-1-yl]-[(3S or 3R)-3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-(2-methylazetidin-1-yl)phenyl]azetidin-1-yl]-[(3R or 3S)-3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-(3-fluoropyrrolidin-1-yl)phenyl]azetidin-1-yl]-[(3R or 3S)-3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; (+)- or (-)-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone; (-)- or (+)-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone; (+)- or (-)-[3-[[2-chloro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (-)- or (+)-[3-[[2-chloro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-(3-fluoropyrrolidin-1-yl)phenyl]azetidin-1-yl]-[(3S or 3R)-3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; 4-[1-[3-[4-(2,2,2-trifluoroethyl)phenyl]azetidine-1-carbonyl]pyrrolidin-3-yl]oxazolidin-2-one; [3-[4-(oxetan-3-yl)phenyl]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; (+)- or (-)-[3-[4-(oxetan-3-yl)phenyl]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; (-)- or (+)-[3-[4-(oxetan-3-yl)phenyl]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; 4-[1-[3-[4-(2,4-difluorophenyl)phenyl]azetidine-1-carbonyl]pyrrolidin-3-yl]oxazolidin-2-one; [3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone; [4-[bis(4-fluorophenyl)methyl]-1-piperidyl]-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; 4-[1-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-carbonyl]pyrrolidin-3-yl]oxazolidin-2-one; (+)- or (-)-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone; (-)- or (+)-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone; (+)- or (-)-[3-(3,3-dimethyl-2H-benzofuran-6-yl)azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; (-)- or (+)-[3-(3,3-dimethyl-2H-benzofuran-6-yl)azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone; (+)- or (-)-[4-[bis(4-fluorophenyl)methyl]-1-piperidyl]-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; (-)- or (+)-[4-[bis(4-fluorophenyl)methyl]-1-piperidyl]-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-chloro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-(2,2,2-trifluoro-1,1-dimethyl-ethoxy)phenyl]azetidin-1-yl]methanone; [3-[[2-fluoro-4-(pentafluoro-λ6-sulfanyl)phenyl]methoxy]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; (+)-[4-[(2-chloro-4-fluoro-phenoxy)methyl]-1-piperidyl]-[(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; (-)-[4-[(2-chloro-4-fluoro-phenoxy)methyl]-1-piperidyl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; (+)- or (-)-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-(2,2,2-trifluoro-1,1-dimethyl-ethoxy)phenyl]azetidin-1-yl]methanone; (-)- or (+)-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-(2,2,2-trifluoro-1,1-dimethyl-ethoxy)phenyl]azetidin-1-yl]methanone; (+)- or (-)-[4-[[2-chloro-4-(trifluoromethyl)phenyl]methoxy]-1-piperidyl]-[(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; (-)- or (+)-[4-[[2-chloro-4-(trifluoromethyl)phenyl]methoxy]-1-piperidyl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3R or 3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[[4-(trifluoromethyl)phenyl]methyl]pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]-8-azabicyclo[3.2.1]octan-8-yl]-[(3R or 3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]-8-azabicyclo[3.2.1]octan-8-yl]-[(3S or 3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3aS,6aR)-5-[2-fluoro-4-(trifluoromethyl)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-[(3R or 3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3aS,6aR)-5-[2-fluoro-4-(trifluoromethyl)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-[(3S or 3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; (-)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3R or 3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; (+)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3R or 3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; (-)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3R or 3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; (+)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3S or 3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; (-)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3S or 3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; (+)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3S or 3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[6-(2-chlorophenoxy)-3-pyridyl]azetidin-1-yl]-[3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3R)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]methanone; [3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[4-[3-(2,2,2-trifluoroethoxy)azetidin-1-yl]phenyl]azetidin-1-yl]methanone; [6-(2-chloro-4-fluoro-phenoxy)-2-azaspiro[3.3]heptan-2-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridyl]azetidin-1-yl]methanone; [(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone; [(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[3-[4-[3-(2,2,2-trifluoroethoxy)azetidin-1-yl]phenyl]azetidin-1-yl]methanone; [6-(2-chloro-4-fluoro-phenoxy)-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]methanone; [(3R)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[6-[6-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; [(3R)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridyl]azetidin-1-yl]methanone; [3-[4-(4-fluorophenoxy)phenyl]azetidin-1-yl]-[3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [3-(tetrazol-1-yl)pyrrolidin-1-yl]-[6-[6-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; [3-(tetrazol-1-yl)pyrrolidin-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridyl]azetidin-1-yl]methanone; (+)- or (-)-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[4-[3-(2,2,2-trifluoroethoxy)azetidin-1-yl]phenyl]azetidin-1-yl]methanone; (-)- or (+)-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[4-[3-(2,2,2-trifluoroethoxy)azetidin-1-yl]phenyl]azetidin-1-yl]methanone; (+)- or (-)-[6-(2-chloro-4-fluoro-phenoxy)-2-azaspiro[3.3]heptan-2-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; (-)- or (+)-[6-(2-chloro-4-fluoro-phenoxy)-2-azaspiro[3.3]heptan-2-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; (+)- or (-)-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridyl]azetidin-1-yl]methanone; (-)- or (+)-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridyl]azetidin-1-yl]methanone; (+)- or (-)-[3-[4-(4-fluorophenoxy)phenyl]azetidin-1-yl]-[3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; (-)- or (+)-[3-[4-(4-fluorophenoxy)phenyl]azetidin-1-yl]-[3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; (+)- or (-)-[3-(tetrazol-1-yl)pyrrolidin-1-yl]-[6-[6-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; (-)- or (+)-[3-(tetrazol-1-yl)pyrrolidin-1-yl]-[6-[6-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; (+)- or (-)-[3-(tetrazol-1-yl)pyrrolidin-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridyl]azetidin-1-yl]methanone; (-)- or (+)-[3-(tetrazol-1-yl)pyrrolidin-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridyl]azetidin-1-yl]methanone; [(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[2-(3,3,3-trifluoropropoxy)spiro[3.3]heptan-6-yl]methanone; [(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone; [3-[4-(4-fluorophenoxy)phenyl]azetidin-1-yl]-[(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-[3-(2,2,2-trifluoroethoxy)azetidin-1-yl]phenyl]azetidin-1-yl]methanone; [6-(2-chloro-4-fluoro-phenoxy)-2-azaspiro[3.3]heptan-2-yl]-[(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridyl]azetidin-1-yl]methanone; [(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[6-[3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidin-1-yl]methanone; [3-[2-(3-chlorophenyl)ethynyl]azetidin-1-yl]-[(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[2-[2-(difluoromethyl)phenyl]ethynyl]azetidin-1-yl]-[(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [4-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]-[rac-(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-[3-chloro-5-(2,2,2-trifluoroethoxy)phenoxy]pyrrolidin-1-yl]-[(3S or 3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-[3-chloro-5-(2,2,2-trifluoroethoxy)phenoxy]pyrrolidin-1-yl]-[(3R or 3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3R)-3-[3-chloro-5-(2,2,2-trifluoroethoxy)phenoxy]pyrrolidin-1-yl]-[(3S or 3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3R)-3-[3-chloro-5-(2,2,2-trifluoroethoxy)phenoxy]pyrrolidin-1-yl]-[(3R or 3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[2-(3,3,3-trifluoropropoxy)spiro[3.3]heptan-6-yl]methanone; [2-[[1-(difluoromethyl)cyclopropyl]methoxy]spiro[3.3]heptan-6-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [8-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-8-azabicyclo[3.2.1]octan-3-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[3-(triazol-1-yl)pyrrolidin-1-yl]methanone; [3-[4-[3-(2,2-dimethylpropyl)triazol-4-yl]phenyl]azetidin-1-yl]-[3-(triazol-1-yl)pyrrolidin-1-yl]methanone; [3-(triazol-1-yl)pyrrolidin-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone; [3-(2-chloro-4-isopropylsulfonyl-phenyl)azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-(4-tert-butylsulfonyl-2-chloro-phenyl)azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[5-(2-chlorophenoxy)pyrazin-2-yl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[6-[6-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone; [3-[6-(2,4-dichlorophenoxy)-3-pyridyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-(4-fluorophenoxy)phenyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-(2-chloro-4-isobutylsulfonyl-phenyl)azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-(benzenesulfonyl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-(2-chloro-4-propylsulfonyl-phenyl)azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-(2-chloro-4-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-(4-tert-butylphenyl)azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; 1-[3-[4-(2-chloro-4-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-(5-tert-butyl-2-pyridyl)azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; 1-[3-[4-(2-chloro-4-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxylic acid; 1-[3-[4-(2,4-difluorophenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxylic acid; 2-[4-[1-[(3S)-3-(1H-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]sulfonylacetonitrile; [3-[4-(N-methylanilino)phenyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-(trifluoromethylsulfonyl)phenyl]azetidin-1-yl]methanone; [3-(4-cyclohexylsulfonylphenyl)azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; 1-[5-[1-[(3S)-3-(1H-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]-2-pyridyl]cyclobutanecarbonitrile; [6-[(2,4-difluorophenyl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [6-[[4-fluoro-2-(trifluoromethyl)phenyl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-[N-(cyclopropylmethyl)anilino]phenyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; 1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(N-phenylanilino)phenyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-(6-tert-butyl-3-pyridyl)azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[6-[(5-methoxy-2-pyridyl)-methyl-amino]-3-pyridyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[6-[(5-ethyl-2-pyridyl)-methyl-amino]-3-pyridyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[6-[(5-cyclopropyl-2-pyridyl)-methyl-amino]-3-pyridyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-(N-methylanilino)phenyl]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[6-(N-methylanilino)-3-pyridyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[6-(4-isopropyl-N-methyl-anilino)-3-pyridyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[6-[(3-ethyl-2-pyridyl)-methyl-amino]-3-pyridyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[6-[N-(cyclopropylmethyl)anilino]-3-pyridyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; (3S)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3R)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[6-[N-(cyclopropylmethyl)anilino]-3-pyridyl]azetidin-1-yl]-[3-(1H-tetrazol-5-yl)pyrrolidin-1-yl]methanone; [3-(1H-tetrazol-5-yl)pyrrolidin-1-yl]-[3-[4-(2,2,2-trifluoro-1,1-dimethyl-ethoxy)phenyl]azetidin-1-yl]methanone; [2-(2-methoxyphenyl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [2-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [2-(2,2-dimethylpropylsulfonyl)-2,6-diazaspiro[3.3]heptan-6-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [2-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]-[(3R)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [2-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [3-[6-[N-(cyclopropylmethyl)anilino]-3-pyridyl]azetidin-1-yl]-[(3S)-3-(1H-tetrazol-5-yl)pyrrolidin-1-yl]methanone; [3-[6-[N-(cyclopropylmethyl)anilino]-3-pyridyl]azetidin-1-yl]-[(3R)-3-(1H-tetrazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-(4-fluorophenoxy)phenyl]azetidin-1-yl]-[3-(1H-tetrazol-5-yl)pyrrolidin-1-yl]methanone; 1-[3-[6-[N-(cyclopropylmethyl)anilino]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(4-fluorophenoxy)phenyl]azetidin-1-yl]-[(3R)-3-(1H-tetrazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-(4-fluorophenoxy)phenyl]azetidin-1-yl]-[(3S)-3-(1H-tetrazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[3-[4-[4-(trifluoromethyl)pyrimidin-2-yl]oxyphenyl]azetidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[3-(1H-tetrazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[6-[6-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-2-azaspiro[3.3]heptan-2-yl]methanone; (3S)-1-[3-[6-[N-(cyclopropylmethyl)anilino]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3R)-1-[3-[6-[N-(cyclopropylmethyl)anilino]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [6-[[4-fluoro-2-(trifluoromethyl)phenyl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[4-[3-(trifluoromethyl)azetidin-1-yl]phenyl]azetidin-1-yl]methanone; 1-[3-[4-(benzenesulfonyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [2-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonan-7-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; 1-[3-[4-[3-(2,2,2-trifluoroethoxy)azetidin-1-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [2-[(2-chloro-4-fluoro-phenyl)methyl]-2,7-diazaspiro[3.5]nonan-7-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [3-[(2-fluoro-4-methylsulfonyl-phenyl)methoxy]azetidin-1-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; 1-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; 1-[3-[4-[3-(trifluoromethyl)azetidin-1-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3R)-3-(1H-tetrazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-tetrazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]methanone; [6-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[[6-(trifluoromethyl)-3-pyridyl]methoxy]azetidin-1-yl]methanone; [3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[[5-(trifluoromethyl)-3-pyridyl]methoxy]azetidin-1-yl]methanone; [3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[6-[[5-(trifluoromethyl)-3-pyridyl]oxy]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-chloro-3-pyridyl)oxy]-2-azaspiro[3.3]heptan-2-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [6-[(6-chloro-3-pyridyl)oxy]-2-azaspiro[3.3]heptan-2-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; (3S)-1-[3-[4-[3-(2,2,2-trifluoroethoxy)azetidin-1-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3R)-1-[3-[4-[3-(2,2,2-trifluoroethoxy)azetidin-1-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-(benzenesulfonyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3R)-1-[3-[4-(benzenesulfonyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[(2-fluoro-4-methylsulfonyl-phenyl)methoxy]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; 2-Cyclopropyl-6-[1-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]oxy-benzonitrile; (3S)-1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[2-[2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptane-6-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[[[3-(trifluoromethyl)phenyl]sulfonylamino]methyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[[[4-(trifluoromethyl)phenyl]sulfonylamino]methyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[6-(trifluoromethyl)-3-pyridyl]oxy]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2,6-diazaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[[6-(trifluoromethyl)-3-pyridyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[[5-(trifluoromethyl)-3-pyridyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[[1-(trifluoromethyl)cyclopropyl]amino]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(3-chloropyridazin-4-yl)oxyphenyl]azetidin-1-yl]-[(3R)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [3-[(2-fluoro-4-methylsulfonyl-phenyl)methoxy]azetidin-1-yl]-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[2-[2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; 1-[4-[1-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]cyclopropanecarbonitrile; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]methanone; N-[2-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptan-6-yl]-1-(trifluoromethyl)cyclopropanecarboxamide; [(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[3-[4-[[1-(trifluoromethyl)cyclopropyl]methylamino]phenyl]azetidin-1-yl]methanone; (3S)-1-[3-[2-[1-(trifluoromethyl)cyclopropyl]pyrimidin-5-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[6-[1-(trifluoromethyl)cyclopropyl]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[[2-(trifluoromethyl)pyrimidin-5-yl]methoxy]azetidin-1-yl]methanone; 1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-N-methyl-pyrrolidine-3-carboxamide; 1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-N-ethyl-pyrrolidine-3-carboxamide; (3S)-1-[3-[4-[[1-(trifluoromethyl)cyclopropyl]amino]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-[[1-(trifluoromethyl)cyclopropyl]methylamino]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[(2-fluoro-4-methylsulfonyl-phenyl)methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[2-(2,4-difluorophenyl)sulfonyl-2,6-diazaspiro[3.3]heptane-6-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[2-[3-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptane-6-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[2-[3-(trifluoromethoxy)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptane-6-carbonyl]pyrrolidine-3-carboxamide; rac-(3S)-1-[3-[5-[3-(trifluoromethyl)pyrrolidin-1-yl]-2-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-N-methyl-pyrrolidine-3-carboxamide; (3R)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-N-methyl-pyrrolidine-3-carboxamide; (3S)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-N-ethyl-pyrrolidine-3-carboxamide; (3R)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-N-ethyl-pyrrolidine-3-carboxamide; [3-[6-(2-chlorophenoxy)-3-pyridyl]azetidin-1-yl]-[(3R)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [3-[4-(4-fluorophenoxy)phenyl]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [3-[5-(2-chlorophenoxy)pyrazin-2-yl]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [(3R)-3-(tetrazol-1-yl)pyrrolidin-1-yl]-[6-[6-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; 2-Cyclopropyl-6-[1-[(3R)-3-(tetrazol-1-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]oxy-benzonitrile; [3-[5-(2-chlorophenoxy)pyrazin-2-yl]azetidin-1-yl]-[(3R)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]-[6-[6-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[4-[3-(2,2-dimethylpropyl)triazol-4-yl]phenyl]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [3-[4-(4-fluorophenoxy)phenyl]azetidin-1-yl]-[(3R)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [3-[5-(2,4-dichlorophenoxy)pyrazin-2-yl]azetidin-1-yl]-[(3R)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; 2-Cyclopropyl-6-[1-[(3S)-3-(tetrazol-1-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]oxy-benzonitrile; Methyl 2,2-dimethyl-3-[3-[1-[(3R)-3-(tetrazol-1-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]oxyphenyl]propanoate; [3-[6-(2-chlorophenoxy)-3-pyridyl]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [3-[4-(4-cyclopropylpyrimidin-2-yl)oxyphenyl]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [3-[5-(2,4-dichlorophenoxy)pyrazin-2-yl]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; 1-[4-[1-[(3R)-3-(tetrazol-1-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]cyclopropanecarbonitrile; [3-[4-(4-cyclopropylpyrimidin-2-yl)oxyphenyl]azetidin-1-yl]-[(3R)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; 1-[4-[1-[(3S)-3-(tetrazol-1-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]cyclopropanecarbonitrile; Methyl 2,2-dimethyl-3-[3-[1-[(3S)-3-(tetrazol-1-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]oxyphenyl]propanoate; [3-[4-[3-(2,2-dimethylpropyl)triazol-4-yl]phenyl]azetidin-1-yl]-[(3R)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3R)-3-hydroxypyrrolidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3R)-3-(hydroxymethyl)pyrrolidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(hydroxymethyl)pyrrolidin-1-yl]methanone; (3S)-1-[6-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; [7-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [7-[2-fluoro-4-(trifluoromethyl)phenoxy]-2-azaspiro[3.5]nonan-2-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [6-[2-fluoro-4-(trifluoromethyl)anilino]-2-azaspiro[3.3]heptan-2-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [6-[[2-fluoro-4-(trifluoromethyl)phenyl]methylamino]-2-azaspiro[3.3]heptan-2-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; (3S)-1-[3-[4-[3-(methylsulfonylmethyl)azetidin-1-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; rac-(3S)-1-[3-[5-[3-(trifluoromethyl)pyrrolidin-1-yl]pyrazin-2-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[3-[4-[3-(trifluoromethyl)azetidin-1-yl]phenyl]azetidin-1-yl]methanone; [6-[[2-fluoro-4-(trifluoromethyl)phenyl]methylamino]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]methanone; [6-[(4,4-difluoro-1-piperidyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [3-[(4,4-difluorocyclohexyl)methoxy]azetidin-1-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; N-[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptan-6-yl]-1-(trifluoromethyl)cyclopropanecarboxamide; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-[[1-(trifluoromethyl)cyclopropyl]amino]phenyl]azetidin-1-yl]methanone; 1-[4-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]cyclopropanecarbonitrile; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[6-[1-(trifluoromethyl)cyclopropyl]-3-pyridyl]azetidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[2-[1-(trifluoromethyl)cyclopropyl]pyrimidin-5-yl]azetidin-1-yl]methanone; [3-[(2-fluoro-4-methylsulfonyl-phenyl)methoxy]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[6-(trifluoromethyl)-3-pyridyl]oxy]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[2-[2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[2-[3-(trifluoromethoxy)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; N-methyl-2-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methyl]benzamide; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[2-[3-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[3-[2-[1-(trifluoromethyl)cyclopropyl]pyrimidin-5-yl]azetidin-1-yl]methanone; N-[[1-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]methyl]-3-(trifluoromethyl)benzenesulfonamide; [3-[4-(3-dimethylphosphorylphenyl)phenyl]azetidin-1-yl]-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[6-(trifluoromethyl)pyridazin-3-yl]oxyazetidin-1-yl]methanone; 1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-sulfonamide; tert-Butyl N-[(3S)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidin-3-yl]carbamate; (3S)-1-[3-[5-(2-chloro-4-methylsulfonyl-phenyl)-2-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; N-[[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]methyl]-3-(trifluoromethyl)benzenesulfonamide; N-[[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]methyl]-4-(trifluoromethyl)benzenesulfonamide; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[2-[4-(trifluoromethoxy)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [3-[5-(2,4-difluorophenyl)-4H-1,2,4-triazol-3-yl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (3S)-1-[3-[5-(4-chloro-2-methylsulfonyl-phenyl)-2-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[5-(2-chloro-4-methylsulfonyl-phenyl)pyrazin-2-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3R)-1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3R)-1-[6-[[6-(trifluoromethyl)-3-pyridyl]oxy]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3R)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; 2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-N-[[1-(trifluoromethyl)cyclopropyl]methyl]-2-azaspiro[3.3]heptane-6-carboxamide; [(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[6-[[[1-(trifluoromethyl)cyclopropyl]amino]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3R)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [3-[4-(benzenesulfonyl)phenyl]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]-[3-[4-[4-(trifluoromethyl)pyrimidin-2-yl]oxyphenyl]azetidin-1-yl]methanone; [3-[6-(2-chlorophenoxy)pyridazin-3-yl]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; Methyl 2-methyl-2-[3-[1-[(3S)-3-(tetrazol-1-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]oxyphenyl]propanoate; [2-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; Methyl 2-methyl-2-[3-[1-[(3R)-3-(tetrazol-1-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]oxyphenyl]propanoate; [(3R)-3-(tetrazol-1-yl)pyrrolidin-1-yl]-[3-[4-[4-(trifluoromethyl)pyrimidin-2-yl]oxyphenyl]azetidin-1-yl]methanone; [2-[4-fluoro-3-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [3-[(2-fluoro-4-methylsulfonyl-phenyl)methoxy]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [2-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]-[(3R)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [3-[4-(dimethylphosphorylmethyl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [7-[2-fluoro-4-(trifluoromethyl)phenoxy]-2-azaspiro[3.5]nonan-2-yl]-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]methanone; (3S)-1-[3-[4-(2-chloro-4-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(2-chloro-4-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-hydroxypyrrolidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-hydroxypyrrolidin-1-yl]methanone; (3S)-1-[3-[4-(6-chloro-4-methylsulfonyl-3-pyridyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (3-Pyrrolidin-1-ylsulfonylpyrrolidin-1-yl)-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone; Morpholino-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone; [3-[5-(4-chloro-2-fluoro-phenoxy)pyrazin-2-yl]azetidin-1-yl]-morpholino-methanone; [3-[[rac-(1S,5R)-6,6-difluoro-3-bicyclo[3.1.0]hexanyl]methoxy]azetidin-1-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [6-[[2-fluoro-4-(trifluoromethyl)phenyl]methylamino]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [7-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [7-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]-[(3R)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [7-[2-fluoro-4-(trifluoromethyl)phenoxy]-2-azaspiro[3.5]nonan-2-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [7-[2-fluoro-4-(trifluoromethyl)phenoxy]-2-azaspiro[3.5]nonan-2-yl]-[(3R)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; (3S)-1-[3-[5-(4-chloro-2-fluoro-phenyl)pyrimidin-2-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[5-(4-chloro-2-fluoro-phenyl)-2-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[5-(2,4-dichlorophenyl)-2-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-(5-chloro-3-methylsulfonyl-2-pyridyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[6-(2-chloro-4-methylsulfonyl-phenyl)-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[6-(4-chloro-2-methylsulfonyl-phenyl)-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(6-chloro-4-methylsulfonyl-3-pyridyl)phenyl]azetidin-1-yl]-[(3S)-3-hydroxypyrrolidin-1-yl]methanone; (3S)-1-[3-[4-[5-(trifluoromethyl)pyrazin-2-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [(3S)-3-aminopyrrolidin-1-yl]-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]methanone; [2-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonan-7-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [2-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonan-7-yl]-[(3R)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; (3S)-1-[7-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3R)-1-[7-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[2-fluoro-4-(trifluoromethyl)phenoxy]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3R)-1-[7-[2-fluoro-4-(trifluoromethyl)phenoxy]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[2-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonane-7-carbonyl]pyrrolidine-3-carboxamide; (3R)-1-[2-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonane-7-carbonyl]pyrrolidine-3-carboxamide; [7-[2-fluoro-4-(trifluoromethyl)phenyl]sulfonyl-2,7-diazaspiro[3.5]nonan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (3S)-1-[7-[2-fluoro-4-(trifluoromethyl)phenyl]sulfonyl-2,7-diazaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; [6-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-fluoro-3-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [6-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3R)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [(3R)-3-(tetrazol-1-yl)pyrrolidin-1-yl]-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-fluoro-3-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3R)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[7-[2-(trifluoromethyl)pyrimidin-4-yl]oxy-2-azaspiro[3.5]nonan-2-yl]methanone; N-[2-[3-(4H-1,2,4-triazol-3-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.5]nonan-7-yl]-3-(trifluoromethoxy)benzenesulfonamide; (3S)-1-[3-[4-(4-chloro-2-fluoro-phenyl)-3-methylsulfonyl-phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; N-[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptan-6-yl]-2-(trifluoromethyl)benzenesulfonamide; N-[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptan-6-yl]-3-(trifluoromethyl)benzenesulfonamide; N-[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptan-6-yl]-4-(trifluoromethyl)benzenesulfonamide; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; (3S)-1-[6-[[2-(trifluoromethyl)phenyl]sulfonylamino]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[3-(trifluoromethyl)phenyl]sulfonylamino]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[4-(trifluoromethyl)phenyl]sulfonylamino]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-(2,2-dimethylpropylsulfonylamino)-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[5-(2-chloro-4-methylsulfonyl-phenyl)pyrimidin-2-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[2-(2-chloro-4-methylsulfonyl-phenyl)pyrimidin-5-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[6-(1,1-dioxo-1,4-thiazinan-4-yl)-3-pyridyl]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[5-(4-chloro-2-methylsulfonyl-phenyl)-2-pyridyl]azetidin-1-yl]-[(3R)-3-hydroxypyrrolidin-1-yl]methanone; [3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; 1-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-sulfonamide; 1-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]piperidine-3-carboxamide; [3-[5-(4-chlorophenoxy)pyrazin-2-yl]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]-[6-[4-(trifluoromethyl)phenyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]-[6-[2-(trifluoromethyl)pyrimidin-5-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[7-[6-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.5]nonan-2-yl]methanone; [7-(4-fluoro-2-methylsulfonyl-phenoxy)-2-azaspiro[3.5]nonan-2-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[3-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-3-pyridyl]azetidin-1-yl]methanone; [3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[7-[6-(trifluoromethyl)pyridazin-3-yl]oxy-2-azaspiro[3.5]nonan-2-yl]methanone; [3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[7-[5-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.5]nonan-2-yl]methanone; [(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[7-[5-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.5]nonan-2-yl]methanone; (3R)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-sulfonamide; (3S)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-sulfonamide; 3-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-4,5-dihydroisoxazole-5-carboxamide; 1-[7-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonane-2-carbonyl]piperidine-3-carboxamide; 1-[7-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-sulfonamide; [6-[(3-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [6-[(4-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (3S)-1-[6-[(3-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[(4-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-3-pyridyl]azetidin-1-yl]methanone; (3S)-1-[3-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; 4-Fluoro-N-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-4-piperidyl]benzenesulfonamide; N-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-4-piperidyl]-4-(trifluoromethyl)benzenesulfonamide; (3S)-1-[4-[[4-(trifluoromethyl)phenyl]sulfonylamino]piperidine-1-carbonyl]pyrrolidine-3-carboxamide; 4-chloro-N-[[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-4-piperidyl]methyl]benzenesulfonamide; (3S)-1-[7-(4-fluoro-2-methylsulfonyl-phenoxy)-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[6-(trifluoromethyl)pyridazin-3-yl]oxy-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[2-(trifluoromethyl)pyrimidin-4-yl]oxy-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[[3-(trifluoromethoxy)phenyl]sulfonylamino]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; N-[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.5]nonan-7-yl]-3-(trifluoromethoxy)benzenesulfonamide; (5S)-3-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-4,5-dihydroisoxazole-5-carboxamide; (5R)-3-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-4,5-dihydroisoxazole-5-carboxamide; 1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]azetidine-3-sulfonamide; 1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]piperidine-4-sulfonamide; N-[[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-4-piperidyl]methyl]-4-(trifluoromethyl)benzenesulfonamide; (3S)-1-[4-[[[4-(trifluoromethyl)phenyl]sulfonylamino]methyl]piperidine-1-carbonyl]pyrrolidine-3-carboxamide; N-[[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-4-piperidyl]methyl]-4-(trifluoromethoxy)benzenesulfonamide; (3S)-1-[4-[[[4-(trifluoromethoxy)phenyl]sulfonylamino]methyl]piperidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-(6,6-difluoro-2-azaspiro[3.3]heptan-2-yl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-[3-(trifluoromethyl)cyclobutyl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-(2-azaspiro[3.4]octan-2-yl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(4-fluoro-2-methylsulfonyl-phenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[6-(3-hydroxy-3-methyl-azetidin-1-yl)-3-pyridyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[6-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]-3-pyridyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[6-[3-hydroxy-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidin-1-yl]-[rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-[1-(1H-tetrazol-5-yl)cyclopropyl]phenyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-[1-(2-tert-butyltetrazol-5-yl)cyclopropyl]phenyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (3S)-1-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[(4-fluoro-2-methylsulfonyl-phenyl)methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[6-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; rac-(3S)-1-[3-[6-[3-hydroxy-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-[1-(2-tert-butyltetrazol-5-yl)cyclopropyl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[1-(trifluoromethyl)cyclopropyl]amino]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[1-(trifluoromethyl)cyclopropyl]amino]-2-azaspiro[3.3]heptan-2-yl]methanone; (3S)-1-[3-[6-[(3R)-3-hydroxy-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[6-[(3S)-3-hydroxy-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(4-fluorophenoxy)phenyl]azetidin-1-yl]-[(3R)-3-(tetrazol-2-yl)pyrrolidin-1-yl]methanone; [(3R)-3-(tetrazol-2-yl)pyrrolidin-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone; [3-[6-[(3R)-3-hydroxy-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[6-[(3S)-3-hydroxy-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[6-(4-chloro-2-methylsulfonyl-phenoxy)-3-pyridyl]azetidin-1-yl]-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]methanone; 1-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-sulfonamide; 1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-sulfonamide; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[[4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[[3-(trifluoromethylsulfonyl)phenyl]methoxy]azetidin-1-yl]methanone; Methyl 2-[4-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]benzoate; 1-[4-[1-[rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]piperidine-2-carboxamide; [3-[[2-fluoro-5-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[[4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]methanone; [(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]-[3-[2-[1-(trifluoromethyl)cyclopropyl]pyrimidin-5-yl]azetidin-1-yl]methanone; (3S)-1-[7-[[5-(trifluoromethyl)pyrazin-2-yl]amino]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3R)-1-[7-[[5-(trifluoromethyl)pyrazin-2-yl]amino]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[5-(trifluoromethyl)pyrimidin-2-yl]oxy-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(4-fluorophenoxy)phenyl]azetidin-1-yl]-[(3S)-3-(tetrazol-2-yl)pyrrolidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(tetrazol-2-yl)pyrrolidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3R)-3-(tetrazol-2-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]-[3-[4-[[1-(trifluoromethyl)cyclopropyl]methoxy]phenyl]azetidin-1-yl]methanone; [(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]-[3-[4-[5-(trifluoromethyl)pyrazin-2-yl]oxyphenyl]azetidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[6-[[1-(trifluoromethyl)cyclopropyl]amino]-3-pyridyl]azetidin-1-yl]methanone; 4,4-Difluoro-1-[4-[1-[rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]piperidine-2-carboxamide; (3S)-1-[7-[5-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; [3-[[5-chloro-2-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[3-chloro-5-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethoxy)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[3-fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-chloro-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; 2-[4-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]benzoic acid; (3S)-1-[3-[4-(3,5-dimethylpyrazol-1-yl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [6-[(3-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [3-[[2-chloro-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [3-[[3-fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethoxy)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [3-[[5-chloro-2-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [3-[[3-chloro-5-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-2-pyridyl]azetidin-1-yl]methanone; (3S)-1-[3-[6-(2-azaspiro[3.4]octan-2-yl)-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; 1-[3-[6-(2-azaspiro[3.4]octan-2-yl)-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-sulfonamide; 1-[4-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]piperidine-2-carboxamide; (3S)-1-[7-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; 2-[4-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]benzamide; (3S)-1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl-methyl-amino]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[[4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[[3-(trifluoromethylsulfonyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[5-[6-(trifluoromethyl)-3-pyridyl]-1,2,4-oxadiazol-3-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[5-[3-(trifluoromethyl)-1-bicyclo[1.1.1]pentanyl]-1,2,4-oxadiazol-3-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; rac-(3S)-1-[3-[6-[3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; N-ethyl-2-[4-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]benzamide; [3-[cyclopropylmethyl-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]amino]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-(3-hydroxyazetidin-1-yl)methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-(3-hydroxy-3-methyl-azetidin-1-yl)methanone; 1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]azetidine-3-carboxamide; 1-[3-[4-[5-(trifluoromethyl)pyrimidin-2-yl]oxyphenyl]azetidine-1-carbonyl]azetidine-3-carboxamide; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl-methyl-amino]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; (3S)-1-[3-(5-spiro[3.3]heptan-2-ylpyrazin-2-yl)azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-[4-methyl-2-(pyrrolidine-1-carbonyl)phenyl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[3-(methylsulfonimidoyl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl-methyl-amino]azetidin-1-yl]-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]methanone; N-[1-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-carbonyl]azetidin-3-yl]methanesulfonamide; N-[1-[3-[4-[[1-(trifluoromethyl)cyclopropyl]methoxy]phenyl]azetidine-1-carbonyl]azetidin-3-yl]methanesulfonamide; N-[1-[3-[4-[5-(trifluoromethyl)pyrazin-2-yl]oxyphenyl]azetidine-1-carbonyl]azetidin-3-yl]methanesulfonamide; N-[1-[3-[6-[3-(trifluoromethyl)azetidin-1-yl]-3-pyridyl]azetidine-1-carbonyl]azetidin-3-yl]methanesulfonamide; (3S)-1-[3-[3-[5-(2,2-dimethylpropyl)-1,3,4-oxadiazol-2-yl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[3-[5-(2,2-dimethylpropyl)-1,3,4-oxadiazol-2-yl]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (3S)-1-[3-[4-[3-(2,2-dimethylpropyl)triazol-4-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; rac-(3S)-1-[3-[6-(2,2-difluoro-5-azaspiro[2.4]heptan-5-yl)-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]-[6-[[6-(trifluoromethyl)pyridazin-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; tert-Butyl 2-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl-methyl-amino]azetidine-1-carbonyl]-2,8-diazaspiro[3.5]nonane-8-carboxylate; N-[1-[2-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonane-7-carbonyl]azetidin-3-yl]methanesulfonamide; (3S)-1-[3-[6-(6-oxa-2-azaspiro[3.4]octan-2-yl)-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[6-(5-oxa-2-azaspiro[3.4]octan-2-yl)-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [7-[[6-(difluoromethoxy)-3-pyridyl]methyl]-2-azaspiro[3.5]nonan-2-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [6-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [6-[[4-fluoro-2-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; N-[1-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-carbonyl]azetidin-3-yl]acetamide; N-[1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]azetidin-3-yl]acetamide; N-[1-[7-[[1-(trifluoromethyl)cyclopropyl]methoxy]-2-azaspiro[3.5]nonane-2-carbonyl]azetidin-3-yl]acetamide; N-[1-[3-[4-[5-(trifluoromethyl)pyrazin-2-yl]oxyphenyl]azetidine-1-carbonyl]azetidin-3-yl]acetamide; (3S)-1-[3-[6-[(3R)-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[6-[(3S)-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-[5-(trifluoromethyl)pyrazin-2-yl]oxyphenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[5-[[1-(trifluoromethyl)cyclopropyl]methylamino]-2-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[5-[[1-(trifluoromethyl)cyclopropyl]methylamino]pyrazin-2-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[6-[3-(trifluoromethyl)azetidin-1-yl]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[2-[3-(trifluoromethyl)azetidin-1-yl]pyrimidin-5-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[(5-chloro-2-pyridyl)methyl]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[[6-(difluoromethoxy)-3-pyridyl]methyl]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[6-(trifluoromethyl)pyridazin-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[2-(trifluoromethyl)pyrimidin-5-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[(6S)-6-[5-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.4]octane-2-carbonyl]pyrrolidine-3-carboxamide; [6-(4-fluorophenyl)-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]-[6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; (3S)-1-[3-[4-(5-cyclobutyl-4H-1,2,4-triazol-3-yl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(triazol-1-yl)pyrrolidin-1-yl]methanone; [3-[6-(2-chlorophenoxy)-3-pyridyl]azetidin-1-yl]-[(3R)-3-(triazol-1-yl)pyrrolidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3R)-3-(triazol-1-yl)pyrrolidin-1-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3R)-3-(triazol-1-yl)pyrrolidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3R)-3-(triazol-2-yl)pyrrolidin-1-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3R)-3-(triazol-2-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl-methyl-amino]azetidin-1-yl]-[(3R)-3-(triazol-2-yl)pyrrolidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(triazol-1-yl)pyrrolidin-1-yl]methanone; [7-[[6-(difluoromethoxy)-3-pyridyl]methyl]-2-azaspiro[3.5]nonan-2-yl]-[(3R)-3-(triazol-1-yl)pyrrolidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(triazol-2-yl)pyrrolidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[6-(triazol-2-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[6-(triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (3S)-1-[3-[4-(3-cyclopropyl-5-methyl-pyrazol-1-yl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-(4-chloro-2-methylsulfonyl-phenyl)-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (3S)-1-[3-[4-(5-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-[5-[1-(trifluoromethyl)cyclopropyl]-4H-1,2,4-triazol-3-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[5-(trifluoromethyl)pyrimidin-2-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[5-(trifluoromethyl)pyrimidin-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; (3S)-1-[6-[[5-(trifluoromethoxy)-2-pyridyl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[5-(trifluoromethoxy)-2-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; rac-(3S)-1-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.4]octane-2-carbonyl]pyrrolidine-3-carboxamide; [rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; (3S)-1-[7-(4-chloro-2-fluoro-phenyl)-2,7-diazaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-(5-chloro-3-fluoro-2-pyridyl)-2,7-diazaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; 1-[4-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]-4-(trifluoromethyl)pyridin-2-one; [3-[4-(3-cyclopropyl-5-methyl-pyrazol-1-yl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[6-[(3R)-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[6-[(3S)-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridyl]azetidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[6-[3-(trifluoromethyl)azetidin-1-yl]-3-pyridyl]azetidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[2-[3-(trifluoromethyl)azetidin-1-yl]pyrimidin-5-yl]azetidin-1-yl]methanone; [3-[4-(2-chloro-4-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[5-(4-chloro-2-methylsulfonyl-phenyl)-2-pyridyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [7-[(5-fluoro-2-pyridyl)methyl]-2-azaspiro[3.5]nonan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[5-[[1-(trifluoromethyl)cyclopropyl]methylamino]pyrazin-2-yl]azetidin-1-yl]methanone; [7-[(5-chloro-2-pyridyl)methyl]-2-azaspiro[3.5]nonan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[7-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2-azaspiro[3.5]nonan-2-yl]methanone; [7-[[6-(difluoromethoxy)-3-pyridyl]methyl]-2-azaspiro[3.5]nonan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[7-[[1-(trifluoromethyl)cyclopropyl]methoxy]-2-azaspiro[3.5]nonan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[7-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[7-[[3-(trifluoromethylsulfonyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [6-[[3-fluoro-5-(trifluoromethyl)-2-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[6-(trifluoromethyl)pyridazin-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[2-(trifluoromethyl)pyrimidin-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[4-fluoro-2-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [6-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [6-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[(6S)-6-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[(6R)-6-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [6-[(4-methylsulfonylphenyl)methyl]-2-azaspiro[3.4]octan-2-yl]-[rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[(6S)-6-[5-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.4]octan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[1-[[4-(trifluoromethyl)phenyl]methyl]azetidin-3-yl]azetidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[5-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[4-(trifluoromethyl)-2-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[7-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2,7-diazaspiro[3.4]octan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[3-[[1-(trifluoromethyl)cyclopropyl]methylamino]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[3-[[[1-(trifluoromethyl)cyclopropyl]amino]methyl]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]methanone; [3-[3-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[3-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]methanone; (4S)-1-[4-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]-4-(trifluoromethyl)piperidin-2-one; (4R)-1-[4-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]-4-(trifluoromethyl)piperidin-2-one; [3-[4-[3-(difluoromethyl)-5-methyl-pyrazol-1-yl]phenyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-(3-tert-butyl-5-methyl-pyrazol-1-yl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (3S)-1-[6-[[3-fluoro-5-(trifluoromethyl)-2-pyridyl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2,7-diazaspiro[3.4]octane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[3-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [6-[[4-methylsulfonyl-3-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [6-[[2-methylsulfonyl-4-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [6-[[3-methylsulfonyl-4-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[3-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[4-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[4-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-[5-[1-(trifluoromethyl)cyclopropyl]-4H-1,2,4-triazol-3-yl]phenyl]azetidin-1-yl]methanone; (3S)-1-[3-[3-[[1-(trifluoromethyl)cyclopropyl]methylamino]-1-bicyclo[1.1.1]pentanyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[3-[[[1-(trifluoromethyl)cyclopropyl]amino]methyl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; rac-(1S,4R,5R)-2-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-2-azabicyclo[2.1.1]hexane-5-carboxamide; (3S)-1-[3-[3-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-(4-chloro-2-methylsulfonyl-phenyl)-2,7-diazaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; [6-[(5-methylsulfonyl-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-[3-(2,2-dimethylpropyl)triazol-4-yl]phenyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[3-(trifluoromethyl)-1,2,4-triazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[4-(trifluoromethyl)oxazol-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[3-(trifluoromethyl)-1,2,4-thiadiazol-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[3-[5-(trifluoromethyl)pyrazin-2-yl]oxy-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[4-(trifluoromethyl)imidazol-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[4-(3,5-diisopropylpyrazol-1-yl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-(3,5-dimethyl-1,2,4-triazol-1-yl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[7-[[5-(trifluoromethyl)-2-pyridyl]amino]-2-azaspiro[3.5]nonan-2-yl]methanone; [6-[(3-fluoro-5-methylsulfonyl-phenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [6-[[4-methylsulfonyl-3-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.4]octan-2-yl]-[rac-(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidin-1-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[7-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.5]nonan-2-yl]methanone; [3-[6-(2-chlorophenoxy)-3-pyridyl]azetidin-1-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [6-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [7-[methyl-[5-(trifluoromethyl)pyrazin-2-yl]amino]-2-azaspiro[3.5]nonan-2-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [6-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[[4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidin-1-yl]methanone; [6-(4-methylsulfonylphenyl)-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[6-[4-(trifluoromethylsulfonyl)phenyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[4-[2-(trifluoromethyl)pyrimidin-5-yl]oxyphenyl]azetidin-1-yl]methanone; [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[7-[[5-(trifluoromethyl)pyrazin-2-yl]amino]-2-azaspiro[3.5]nonan-2-yl]methanone; [7-(5-chloro-2-methylsulfonyl-phenoxy)-2-azaspiro[3.5]nonan-2-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [3-[4-(3,5-dimethylpyrazol-1-yl)phenyl]azetidin-1-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [3-[6-(N-methylanilino)-3-pyridyl]azetidin-1-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; 2-Methoxy-4-[[2-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]benzonitrile; [3-[4-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]phenyl]azetidin-1-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [3-[6-(4-fluorophenoxy)-3-pyridyl]azetidin-1-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [3-(4-cyclopropyl-2-fluoro-phenoxy)azetidin-1-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [3-(4-chloro-3-cyclopropyl-phenoxy)azetidin-1-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [3-[4-[5-[(1-methylcyclopropyl)methyl]-4H-1,2,4-triazol-3-yl]phenyl]azetidin-1-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[4-(trifluoromethyl)thiazol-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; (3S)-1-[6-[[4-(trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[4-(trifluoromethyl)imidazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[3-(trifluoromethyl)-1,2,4-triazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[4-(trifluoromethyl)oxazol-2-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[3-(trifluoromethyl)-1,2,4-thiadiazol-5-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[4-(trifluoromethyl)thiazol-2-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; [6-[(5-fluoro-3-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [6-[(2-fluoro-4-methylsulfonyl-phenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [6-([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (3S)-1-[6-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; [6-(1H-pyrazolo[4,3-b]pyridin-5-ylmethyl)-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[1-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; 3-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]-5-(trifluoromethyl)benzonitrile; 4-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]-2-(trifluoromethyl)benzonitrile; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[6-(trifluoromethoxy)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[3-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(4-cyclopropylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[3-[[6-(trifluoromethyl)-3-pyridyl]methyl]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]methanone; [6-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]methanone; [6-[[4-fluoro-2-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]methanone; [6-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]methanone; [6-[(3-chloro-5-fluoro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]methanone; [3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]-[6-[[5-(trifluoromethoxy)-2-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-fluoro-5-(trifluoromethyl)-2-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]methanone; [3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]-[7-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2,7-diazaspiro[3.4]octan-2-yl]methanone; [7-[(5-chloro-2-pyridyl)methyl]-2-azaspiro[3.5]nonan-2-yl]-[3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]methanone; [7-[[6-(difluoromethoxy)-3-pyridyl]methyl]-2-azaspiro[3.5]nonan-2-yl]-[3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]methanone; [3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone; [3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]-[3-[4-[3-(trifluoromethyl)azetidin-1-yl]phenyl]azetidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]methanone; [3-[4-[5-[(1-methylcyclopropyl)methyl]-4H-1,2,4-triazol-3-yl]phenyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[3-(5-cyclopropyl-1H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; (3S)-1-[3-[4-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [4-[(2-chloro-4-methylsulfonyl-phenyl)methoxy]-1-piperidyl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (3S)-1-[4-[(2-chloro-4-methylsulfonyl-phenyl)methoxy]piperidine-1-carbonyl]pyrrolidine-3-carboxamide; [4-[[4-methylsulfonyl-3-(trifluoromethyl)phenoxy]methyl]-1-piperidyl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (3S)-1-[4-[[4-methylsulfonyl-3-(trifluoromethyl)phenoxy]methyl]piperidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[3-(5-cyclopropyl-3-methyl-pyrazol-1-yl)-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[3-(3,5-dimethylpyrazol-1-yl)-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [4-[[2-fluoro-4-(trifluoromethoxy)phenyl]methoxy]-1-piperidyl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [4-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]-1-piperidyl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (3S)-1-[4-[[2-fluoro-4-(trifluoromethoxy)phenyl]methoxy]piperidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[4-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]piperidine-1-carbonyl]pyrrolidine-3-carboxamide; Methyl 5-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]-2-(trifluoromethoxy)benzoate; [4-[[2-methylsulfonyl-4-(trifluoromethyl)phenoxy]methyl]-1-piperidyl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[4-(5-cyclopropyl-1H-1,2,4-triazol-3-yl)piperazin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[5-(trifluoromethylsulfonyl)-2-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-chlorooxazolo[4,5-b]pyridin-2-yl)piperazin-1-yl]-[3-[[2-fluoro-4-(trifluoromethoxy)phenyl]methoxy]azetidin-1-yl]methanone; 4-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]benzenesulfonamide; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[5-[3-(trifluoromethyl)azetidin-1-yl]pyrazin-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[6-[[5-[[1-(trifluoromethyl)cyclopropyl]methylamino]pyrazin-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[6-[[4-[3-(trifluoromethyl)azetidin-1-yl]sulfonylphenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[(6S)-6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[(6R)-6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[(6S)-6-[[3-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[(6R)-6-[[3-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [6-[[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [6-[[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [6-[[1-methyl-5-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [6-[[2-methyl-4-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; 4-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]-2-(trifluoromethoxy)benzamide; [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-2-pyridyl]azetidin-1-yl]methanone; [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[[6-(trifluoromethyl)-3-pyridyl]methoxymethyl]azetidin-1-yl]methanone; [3-[4-(1-methylsulfonylcyclopropyl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [4-[(3-chloro-5-methylsulfonyl-phenoxy)methyl]-1-piperidyl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; 5-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]-2-(trifluoromethoxy)benzamide; [rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-(trifluoromethylsulfonimidoyl)phenyl]azetidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[3-[[5-(trifluoromethyl)pyrazin-2-yl]amino]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]methanone; Methyl 4-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]-2-(trifluoromethoxy)benzoate; [4-[[2-methylsulfonyl-4-(trifluoromethoxy)phenoxy]methyl]-1-piperidyl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[4-[[6-(trifluoromethyl)-3-pyridyl]methoxymethyl]-1-piperidyl]methanone; [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[4-[[6-(trifluoromethyl)-3-pyridyl]oxymethyl]-1-piperidyl]methanone; [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[4-[[6-(trifluoromethyl)-3-pyridyl]methoxy]-1-piperidyl]methanone; [4-[[4-fluoro-3-(trifluoromethyl)phenoxy]methyl]-1-piperidyl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [4-[[3-fluoro-5-(trifluoromethyl)phenoxy]methyl]-1-piperidyl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [3-(3-isobutyl-1H-pyrazol-5-yl)pyrrolidin-1-yl]-[6-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[6-[[5-(trifluoromethylsulfonyl)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-fluoro-5-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; N'-[2-[3-[1-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]-1-bicyclo[1.1.1]pentanyl]acetyl]cyclopropanecarbohydrazide; [4-[[2-methylsulfonyl-4-(trifluoromethoxy)phenyl]methoxy]-1-piperidyl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (3S)-1-[4-[[2-methylsulfonyl-4-(trifluoromethoxy)phenyl]methoxy]piperidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[3-(4-chloro-2-methylsulfonyl-phenyl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; 2-Methoxy-4-[[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-4-piperidyl]oxymethyl]benzonitrile; (3S)-1-[2-(4-chloro-2-methylsulfonyl-phenyl)-6-azaspiro[3.4]octane-6-carbonyl]pyrrolidine-3-carboxamide; 2-Methoxy-4-[[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-4-piperidyl]oxymethyl]benzamide; (3S)-1-[3-[3-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[2-[(4-chloro-2-methylsulfonyl-phenyl)methyl]-6-azaspiro[3.4]octane-6-carbonyl]pyrrolidine-3-carboxamide; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[3-(trifluoromethoxy)phenyl]sulfonyl-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[7-[3-(trifluoromethyl)phenyl]sulfonyl-2-azaspiro[3.5]nonan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[7-[4-(trifluoromethyl)phenyl]sulfonyl-2-azaspiro[3.5]nonan-2-yl]methanone; [3-[3-(4-fluorophenyl)-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[3-(4-methylsulfonylphenyl)-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[4-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[3-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(methylsulfonimidoyl)-5-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethylsulfonimidoyl)phenyl]methoxy]azetidin-1-yl]-[rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[4-[[5-(trifluoromethyl)pyrazin-2-yl]amino]cuban-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[3-(trifluoromethoxy)phenyl]sulfonimidoyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-fluoro-5-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[7-[[4-(trifluoromethyl)phenyl]sulfonimidoyl]-2-azaspiro[3.5]nonan-2-yl]methanone; [rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[7-[[3-(trifluoromethyl)phenyl]sulfonimidoyl]-2-azaspiro[3.5]nonan-2-yl]methanone; [3-[4-[2-(methylsulfonimidoyl)phenyl]phenyl]azetidin-1-yl]-[rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[(8R)-8-methyl-8-oxo-8lambda 6-thia-9-azatricyclo[8.4.0.02,7]tetradeca-1(10),2(7),3,5,8,11,13-heptaen-12-yl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[(8S)-8-methyl-8-oxo-8lambda 6-thia-9-azatricyclo[8.4.0.02,7]tetradeca-1(10),2(7),3,5,8,11,13-heptaen-12-yl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[3-(4-fluoro-2-methylsulfonyl-phenyl)-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[3-[3-(trifluoromethoxy)phenyl]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]methanone; [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[4-[[5-(trifluoromethyl)-2-pyridyl]methyl]piperazin-1-yl]methanone; [4-[(2-methyloxazol-4-yl)methyl]piperazin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [4-[(4-methylthiazol-5-yl)methyl]piperazin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [4-[(5-chloro-1,3-dimethyl-pyrazol-4-yl)methyl]piperazin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; 4-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptan-6-yl]oxy]-2-(trifluoromethyl)benzonitrile; 5-Fluoro-2-[3-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]-1-bicyclo[1.1.1]pentanyl]benzonitrile; [3-[3-(3-methyl-1H-pyrazol-5-yl)-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [6-[[1-methyl-4-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[3-[4-(trifluoromethylsulfonyl)phenyl]-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]methanone; [3-[3-(4-chloro-2-methylsulfonyl-phenyl)-1-bicyclo[1.1.1]pentanyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [6-[(5-chloro-1,3-dimethyl-pyrazol-4-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; 5-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptan-6-yl]oxy]-2-(trifluoromethyl)benzonitrile; [6-[(5-fluoro-2-pyridyl)oxy]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [6-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]oxy-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[[5-(trifluoromethyl)pyrazin-2-yl]amino]-1-bicyclo[1.1.1]pentanyl]methanone; (3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[4-(trifluoromethylsulfonimidoyl)phenoxyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[6-[[3-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[6-[[3-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[6-[[3-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; 5-[[2-[(3S)-3-(1H-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]-2-(trifluoromethyl)benzonitrile; (3S)-1-[6-[[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[1-methyl-5-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[3-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[4-cyano-3-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[6-(trifluoromethoxy)-3-pyridyl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; 5-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]-2-(trifluoromethyl)benzonitrile; [(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[6-[[4-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[6-[[4-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; rac-(3S)-1-[6-[[2-fluoro-4-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; [6-[[2-fluoro-4-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[rac-(3S)-3-(1H-triazol-4-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-triazol-4-yl)pyrrolidin-1-yl]-[6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-fluoro-5-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-triazol-4-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(1H-triazol-4-yl)pyrrolidin-1-yl]-[6-[[5-(trifluoromethyl)-1H-pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; and [6-[[2-Fluoro-4-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[rac-(3S)-3-(1H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone The present invention provides a compound of formula (I) as described herein, selected from:

[0164] In a preferred embodiment, the present invention provides: [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; 1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; (+)- or (-)-[2-(2-chloro-4-fluoro-phenoxy)-7-azaspiro[3.5]nonan-7-yl]-[(3R)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-imidazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[3-chloro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[[2-chloro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (-)- or (+)-[3-[[2,4-bis(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; (+)- or (-)-1-[3-[4-(2,4-difluorophenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (+)- or (-)-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone; (-)- or (+)-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone; and 4-[1-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-carbonyl]pyrrolidin-3-yl]oxazolidin-2-one or a pharmaceutically acceptable salt thereof.

[0165] In certain embodiments, the present invention provides pharmaceutically acceptable salts, particularly hydrochloride salts, of compounds according to formula (I) described herein. In more particular embodiments, the present invention provides compounds according to formula (I) described herein as the free base.

[0166] In some embodiments, compounds of formula (I) are isotopically labeled by replacing one or more atoms therein with atoms having different atomic masses or mass numbers. Such isotopically labeled (i.e., radiolabeled) compounds of formula (I) are considered to be within the scope of the present disclosure. Exemplary isotopes that can be incorporated into compounds of formula (I) include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, and iodine, respectively, e.g., 2 H, 3 H, 11 C. 13 C. 14C. 13 N, 15 N, 15 O. 17 O. 18 O. 31 P, 32 P, 35 S, 18 F, 36 Cl, 123 I, and 125 Certain isotopically labeled compounds of formula (I), for example, those incorporating a radioactive isotope, are useful in drug and / or substrate tissue distribution studies. The radioactive isotope tritium, i.e., 3 H and carbon-14, i.e., 14 C are particularly useful for this purpose given their ease of incorporation and ready means of detection. For example, compounds of formula (I) can be enriched with 1, 2, 5, 10, 25, 50, 75, 90, 95, or 99% of a given isotope.

[0167] Heavier isotopes, such as deuterium, i.e. 2 Substitutions such as H may result in greater metabolic stability, for example, a longer in vivo half-life or reduced dosage requirements, which may result in certain therapeutic advantages.

[0168] 11 C. 18 F, 15 O and 13 Substitution with positron-emitting isotopes, such as N, can be useful in Positron Emission Topography (PET) studies for examining substrate receptor occupancy. Isotopically labeled compounds of formula (I) can generally be prepared by conventional techniques known to those skilled in the art, or by methods analogous to those described in the Examples set forth below, by substituting an appropriate isotopically labeled reagent for a previously employed non-isotopically labeled reagent.

[0169] Manufacturing Method The preparation of the compounds of formula (I) of the present invention can be carried out by sequential or convergent synthetic routes. The synthesis of the present invention is shown in the following general scheme. The techniques required to carry out the reactions and purification of the resulting products are known to those skilled in the art. The substituents and indices used in the following process descriptions have the meanings given herein unless otherwise indicated.

[0170] If one of the starting materials, intermediates, or compounds of formula (I) contains one or more functional groups that are not stable or reactive under the reaction conditions of one or more reaction steps, suitable protecting groups (e.g., as described in "Protective Groups in Organic Chemistry," T.W. Greene and P.G.M. Hutts, 5th Edition (2014), John Wiley & Sons, New York) can be introduced prior to a critical step by applying methods well known in the art. Such protecting groups can be removed at a later stage of the synthesis using standard methods described in the literature.

[0171] When the starting material or intermediate contains a stereocenter, the compound of formula (I) can be obtained as a mixture of diastereomers or enantiomers, which can be separated by methods well known in the art, such as chiral HPLC, chiral SFC, or chiral crystallization. Racemates can be separated into their antipodes via diastereomeric salts, for example, by crystallization with an optically pure acid, or by separating the antipodes by specific chromatographic methods using either a chiral adsorbent or a chiral eluent. Starting materials and intermediates containing a stereocenter can also be separated to obtain diastereomerically / enantiomerically enriched starting materials and intermediates. The use of such diastereomerically / enantiomerically enriched starting materials and intermediates in the synthesis of the compound of formula (I) typically results in the respective diastereomerically / enantiomerically enriched compounds of formula (I).

[0172] Those skilled in the art will recognize that in the synthesis of compounds of formula (I) (unless otherwise desired), an "orthogonal protecting group strategy" can be applied to cleave several protecting groups one at a time without affecting other protecting groups in the molecule. The principle of orthogonal protection is well known in the art and has been described in the literature (e.g., Barany and R.B. Merrifield, J. Am. Chem. Soc. (1977) 99:7363; H. Waldmann et al., Angew. Chem. Int. Ed. Engl. (1996) 35:2056).

[0173] Those skilled in the art will recognize that the reaction sequence may vary depending on the reactivity and nature of the intermediates.

[0174] More specifically, compounds of formula (I) can be prepared by the methods described below, the methods described in the Examples, or similar methods. Appropriate reaction conditions for the individual reaction steps are known to those skilled in the art. For literature-described reaction conditions that affect the described reactions, see, for example, "Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 2nd Edition, Richard C. Larock, John Wiley & Sons, New York, NY, 1999." The reactions could be easily carried out with or without a solvent. There are no particular restrictions on the nature of the solvent used, so long as it does not adversely affect the reaction or the reagents involved and is capable of dissolving the reagents to at least some extent. The described reactions can occur over a wide range of temperatures, and the exact reaction temperature is not critical to the present invention. It is convenient to carry out the described reactions at temperatures ranging from -78°C to reflux. The reaction time required can also vary widely, depending on many factors, particularly the reaction temperature and the nature of the reagents. However, a period of 0.5 hours to several days is usually sufficient to produce the described intermediates and compounds. The reaction sequence is not limited to the sequence shown in the scheme, but the order of the reaction steps can be freely changed depending on the starting materials and their respective reactivities.

[0175] If the starting materials or intermediates are not commercially available or their synthesis is not described in the literature, they can be prepared analogously to existing procedures for similar analogs or as outlined in the experimental section.

[0176] The following abbreviations are used herein:

[0177] AcOH = acetic acid, ACN = acetonitrile, Bn = benzyl, Boc = tert-butyloxycarbonyl, CAS RN = Chemical Abstracts Registry Number, Cbz = benzyloxycarbonyl, CPME = cyclopentyl methyl ether, Cs2CO3 = cesium carbonate, CO = carbon monoxide, CuCl = copper(I) chloride, CuCN = copper(I) cyanide, CuI = copper(I) iodide, DAST = (diethylamino)sulfur trifluoride, DCM = DCM, DBU = 1,8-diazabicyclo[5,4,0]undec-7-ene, DEA = diethylamine, DEAD = diethyl azodicarboxylate, DIAD = diisopropyl azodicarboxylate, DMAP = 4-dimethylaminopyridine, DME = dimethoxyethane, DMEDA = N,N'-dimethyl-1,2-ethanediamine, D MF = N,N-dimethylformamide, DIPEA = N,N-diisopropylethylamine, dppf = 1,1-bis(diphenylphosphino)ferrocene, EDC.HCl = N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride, EI = electron impact, ESI = electrospray ionization, EtOAc = ethyl acetate, EtOH = ethanol, h = hour, FA = formic acid, H2O = water, H2SO4 = sulfuric acid, HATU = 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate, HBTU = O-benzotriazole-N,N,N'N'-Tetramethyl-uronium-hexafluorophosphate, HCl = hydrogen chloride, HOBt = 1-hydroxy-1H-benzotriazole, HPLC = high performance liquid chromatography, iPrMgCl = isopropyl magnesium chloride, I2 = iodine, IPA = 2-propanol, ISP = positive ion spray (mode), ISN = negative ion spray (mode), K2CO3 = potassium carbonate, KHCO3 = potassium bicarbonate, KI = potassium iodide, KOtBu = potassium tert-butoxide, KOH = potassium hydroxide, K3PO4 = lithium tripotassium phosphate, LiAlH4 or LAH = lithium aluminum hydride, LiHMDS = lithium bis(trimethylsilyl)amide, LiOH = lithium hydroxide, mCPBA = metachloroperbenzoic acid, MgSO4 = magnesium sulfate, min = minute, mL = milliliter, MPLC = medium pressure liquid chromatography, MS = mass spectrum, MTBE = methyl tert-butyl ether, nBuLi = n-butyllithium, NaBH3CN = sodium cyanoborohydride, NaH = sodium hydride, NaHCO3 = sodium bicarbonate, NaN O2 = sodium nitrite, NaBH(OAc)3 = sodium triacetoxyborohydride, NaOH = sodium hydroxide, Na2CO3 = sodium carbonate, Na2SO4 = sodium sulfate, Na2S2O3 = sodium thiosulfate, NBS = N-bromosuccinimide, nBuLi = n-butyllithium, NEt3 = triethylamine (TEA), NH4Cl = ammonium chloride, NMP = N-methyl-2-pyrrolidone, OAc = acetoxy, T3P = propylphosphonic anhydride, PE = petroleum ether, PG = protecting group, Pd-C = palladium-activated Carbon, PdCl2(dppf)-DCM = 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) DCM complex, Pd2(dba)3 = tris(dibenzylideneacetone)dipalladium(0), Pd(OAc)2 = palladium(II) acetate, Pd(OH)2 = palladium hydroxide, Pd(PPh3)4 = tetrakis(triphenylphosphine)palladium(0), PTSA = p-toluenesulfonic acid, R = any group, RT = room temperature, SFC = supercritical fluid chromatography, S-PHOS = 2-dicyclohexylphosphino-2'6'-Dimethoxybiphenyl, TBAI = tetrabutylammonium iodide, TBME = tert-butyl methyl ether, TEA = triethylamine, TFA = trifluoroacetic acid, THF = tetrahydrofuran, TMEDA = N,N,N',N'-tetramethylethylenediamine, ZnCl2 = zinc chloride, Hal = halogen.

[0178] A, B, L, R 1 , R 2 , R 3 , R 4 Compounds of formula IA, where p and q are described herein, can be synthesized analogously to literature procedures and / or as shown, for example, in Scheme 1. [ka] Scheme 1

[0179] Thus, compound 1 is reacted with intermediate 2 in the presence of a urea-forming reagent, such as bis(trichloromethyl)carbonate, using a suitable base and a solvent, such as sodium bicarbonate in DCM, to obtain a compound of formula IA (step a). Additional urea-forming reagents include, but are not limited to, phosgene, trichloromethyl chloroformate, (4-nitrophenyl)carbonate, 1,1'-carbonyl-di-(1,2,4-triazole), or 1,1'-carbonyldiimidazole. This type of reaction and the use of these reagents have been widely described in the literature (e.g., G. Sartori et al., Green Chemistry 2000, 2, 140). Those skilled in the art will recognize that the order of addition of reagents can be important in this type of reaction due to the reactivity and stability of the carbamoyl chloride formed as an intermediate, and to avoid the formation of undesired symmetrical urea by-products.

[0180] Compounds of formula IA can be obtained as mixtures of diastereomers or enantiomers, which can be separated by methods well known in the art, such as chiral HPLC, chiral SFC, or chiral crystallization. Racemates can be separated into their antipodes via diastereomeric salts, for example, by crystallization with optically pure acids, or by separating the antipodes by specific chromatographic methods using either chiral adsorbents or chiral eluents.

[0181] R 4 is a five-membered heteroaromatic system containing a nitrogen atom that can be alkylated, compound IA can be reacted with a suitable alkylating agent, such as iodomethane, using a base such as Na2CO3, K2CO3, NaH or KotBu in a suitable solvent, such as THF or DMF, to provide compound IA.

[0182] A, B, L, R 1 , R 2 , R 3 , R 4 Compounds of formula IB, where p and q are described herein, can be synthesized analogously to literature procedures and / or as shown, for example, in Scheme 2. [ka] Scheme 2

[0183] Thus, intermediate 2 can be coupled with an activated form of carboxylic acid 3a (G = OH) or carboxylic acid chloride 3b (G = Cl) to give compound IB (step a). This type of amide coupling with carboxylic acids has been widely described in the literature and can be achieved by using coupling reagents such as CDI, DCC, HATU, HBTU, HOBT, TBTU, T3P, or Mukaiyama's reagent (Mukaiyama T. Angew. Chem., Int. Ed. Engl. 1979, 18, 707), optionally in the presence of a base (e.g., TEA, DIPEA (Huenig's base), or DMAP) in a suitable solvent such as DMF, DMA, DCM, or dioxane.

[0184] Alternatively, carboxylic acids 3a can be converted to their acid chlorides 3b, for example, by treatment with thionyl chloride or oxalyl chloride, neat or optionally in a solvent such as DCM. Subsequent reaction of the acid chloride with intermediate 1 in a suitable solvent such as DCM or DMF and a base (e.g., TEA, Hunig's base, pyridine, DMAP, or lithium bis(trimethylsilyl)amide) at a temperature ranging from 0° C. to the reflux temperature of the solvent or solvent mixture provides compound IB (step a).

[0185] Compounds of formula IB can be obtained as mixtures of diastereomers or enantiomers, which can be separated by methods well known in the art, such as chiral HPLC, chiral SFC, or chiral crystallization. Racemates can be separated into their antipodes via diastereomeric salts, for example, by crystallization with optically pure acids, or by separating the antipodes by specific chromatographic methods using either chiral adsorbents or chiral eluents.

[0186] R 4 When is a five-membered heteroaromatic system containing a nitrogen atom that can be alkylated, compound IB is reacted with an appropriate alkylating agent, such as iodomethane, using a base such as Na2CO3, K2CO3, NaH, or KotBu to give compound IB.

[0187] A, B, R 1 , R 2 , R 3 , R 4 Compounds of formula IC, where p and q are described herein, can be synthesized analogously to literature procedures and / or as shown, for example, in Scheme 3. [ka] Scheme 3

[0188] Thus, intermediate 4, which is commercially available or prepared by methods known in the art, where X is bromide or iodide, can be subjected to a cross-coupling reaction, such as a Suzuki, Buchwald-Hartwig, Negishi, Heck, Stille, or Sonogashira coupling reaction, with intermediate 5, which is commercially available or prepared by methods known in the art.

[0189] For example, intermediate 4 can be obtained commercially or by reaction with a suitable catalyst (e.g., dichloro[1,1'-bis(diphenylphosphino)-ferrocene]palladium(II) DCM adduct, tetrakis(triphenylphosphine)palladium(0) or palladium(II) acetate with triphenylphosphine) in a suitable solvent (e.g., dioxane, dimethoxyethane, water, toluene, DMF or mixtures thereof) and a suitable base (e.g., Na2CO3, NaHCO3, KF, K2CO3 or TEA) at a temperature between room temperature and the boiling point of the solvent or solvent mixture. The reaction of intermediate 5, in which FG represents an aryl or heteroarylboronic acid (FG = B(OH)2) or a boronic acid ester (FG = e.g., 4,4,5,5-tetramethyl-2-phenyl-1,3,2-dioxaborolane (pinacol) ester), prepared using literature procedures such as those described in "The Journal of Organomethology," can give compound IC (step a). This type of Suzuki reaction has been widely described in the literature (e.g., A. Suzuki, Pure Appl. Chem. 1991, 63, 419-422; A. Suzuki, N. Miyaura, Chem. Rev. 1995, 95, 2457-2483; A. Suzuki, J. Organomet. Chem. 1999, 576, 147-168; V. Polshettiwar et al., Chem. Sus. Chem. 2010, 3, 502-522) and is well known to those skilled in the art.Alternatively, aryl- or heteroaryl-trifluoroborate 19c (FG = BF3) can be used in a cross-coupling reaction applying a palladium catalyst such as, for example, tetrakis(triphenylphosphine)-palladium(0), palladium(II) acetate or dichloro[1,1'-bis(diphenylphosphino)ferrocene]-palladium(II) DCM adduct in a solvent such as toluene, THF, dioxane, water or a mixture thereof, in the presence of a suitable base such as cesium carbonate or potassium phosphate at a temperature between room temperature and the boiling point of the solvent or solvent mixture (step a).

[0190] For example, intermediate 4 can be reacted with intermediate 5 (FG is Sn(alkyl)3, where alkyl is optionally n-butyl or methyl) using a suitable catalyst and solvent, such as tetrakis(triphenylphosphine)-palladium(0), in DMF at a temperature between room temperature and the boiling point of the solvent or solvent mixture to give intermediate 10 (step a). Stille reactions of this type are well known in the art and have been described in literature such as Org. React. 1997, 50, 1-652, ACS Catal. 2015, 5, 3040-3053.

[0191] For example, intermediate 4 can be reacted with intermediate 5 (FG is ZnHal and Hal, preferably bromide or iodide), either commercially available or prepared by literature methods, using a suitable catalyst and solvent system, such as [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) and copper(I) iodide in DMA, or tetrakis(triphenylphosphine)palladium(0) in THF or DMF, at a temperature between room temperature and the boiling point of the solvent, to give intermediate 10 (step a). This type of Negishi reaction is well known in the art and has been described in literature, such as Org. Lett., 2005, 7, 4871; ACS Catal. 2016, 6, 1540-1552; Acc. Chem. Res. 1982, 15, pp. 340-348. Alternatively, intermediate 10 may be prepared by first converting intermediate 8, where X is, for example, an iodide, to the corresponding zinc species by applying literature methods (e.g., reaction of 8 with Zn powder in the presence of chlorotrimethylsilane and 1,2-dibromoethane in a suitable solvent such as DMA), followed by coupling the zinc species with an aryl- or heteroaryl bromide- or iodide under the conditions described above.

[0192] Alternatively, intermediate 4, where X is preferably bromide, can be subjected to cross-electrophilic coupling with aryl- or heteroaryl bromides 5, where FG represents bromide, using a suitable photocatalyst such as nickel catalysts like [Ir{dF(CF)ppy}(dtbpy)]PF ([4,4'-bis(1,1-dimethylethyl)-2,2'-bipyridine-N,N']bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate), NiCl glyme (dichloro(dimethoxyethane)nickel), 4,4'-di-tert-butyl-2,2'-dipyridyl, and tris(trimethylsilyl)silane in the presence of a suitable base such as anhydrous sodium carbonate in a solvent such as DME under irradiation with a 420 nm blue light lamp. This type of reaction is described in the literature, such as J. Am. Chem. Soc. 2016, 138, 8084 (step a).

[0193] Alternatively, intermediate 4, where X is iodide, bromide, chloride or OTf, can be reacted with intermediate 5, where FG denotes a functional group such as RC=CH or RC≡CH, to give compound IC by applying one of the cross-coupling methods described above (step a).

[0194] Compounds of formula IC can be obtained as mixtures of diastereomers or enantiomers, which can be separated by methods well known in the art, such as chiral HPLC, chiral SFC, or chiral crystallization. Racemic compounds can be separated into their antipodes via diastereomeric salts, for example, by crystallization with optically pure acids, or by separating the antipodes by specific chromatographic methods using either chiral adsorbents or chiral eluents.

[0195] R 4When is a five-membered heteroaromatic system containing a nitrogen atom that can be alkylated, compound IC was reacted with an appropriate alkylating agent, such as iodomethane, using a base such as Na2CO3, K2CO3, NaH, or KotBu to give compound IC.

[0196] In some embodiments, intermediate 1 is an intermediate of type 1a. 1 , R 2 , R 3 Intermediate 1a, where A and B are as described herein, can be prepared by methods known in the art and as exemplified by the general synthetic procedure outlined in Scheme 4. [ka] Scheme 4

[0197] Intermediate 2a, which is commercially available or prepared by methods known in the art, where PG represents a suitable protecting group and X represents bromide or iodide, can be subjected to a cross-coupling reaction, such as a Negishi, Heck, Stille, Suzuki, Sonogashira, or Buchwald-Hartwig coupling reaction, with compound 8a, which is commercially available or prepared by methods known in the art, where FG represents a suitable functional group, such as chloro, bromo, iodo, -OSO2 alkyl (e.g., mesylate (methanesulfonic acid)), -OSO2 fluoroalkyl (e.g., triflate (trifluoromethanesulfonic acid)), or -OSO2 aryl (e.g., tosylate (p-toluenesulfonic acid)). This type of reaction has been widely described in the literature and is well known to those skilled in the art (Step a).

[0198] For example, intermediate 2a, in which X is preferably bromide or iodide, can be obtained commercially or by reaction with a suitable catalyst (e.g., dichloro[1,1'-bis(diphenylphosphino)-ferrocene]palladium(II) DCM adduct, tetrakis(triphenylphosphine)palladium(0) or palladium(II) acetate with triphenylphosphine) in a suitable solvent (e.g., dioxane, dimethoxyethane, water, toluene, DMF or mixtures thereof) and a suitable base (e.g., Na2CO3, NaHCO3, KF, K2CO3 or TEA) at a temperature between room temperature and the boiling point of the solvent or solvent mixture, either commercially available or as described, for example, in "Boronic Acids - Preparation and Applications in Organic Synthesis and Intermediate 4a can be obtained by reacting intermediate 8a, where FG represents a functional group such as a boronic acid (FG = B(OH)2) or a boronate ester (FG = e.g., 4,4,5,5-tetramethyl-2-phenyl-1,3,2-dioxaborolane (pinacol) ester), prepared using literature procedures such as those described in "The Journal of Organometries in Medicine" (Step a). This type of Suzuki reaction has been widely described in the literature (e.g., A. Suzuki, Pure Appl. Chem. 1991, 63, 419-422; A. Suzuki, N. Miyaura, Chem. Rev. 1995, 95, 2457-2483; A. Suzuki, J. Organomet. Chem. 1999, 576, 147-168; V. Polshettiwar et al., Chem. Sus. Chem. 2010, 3, 502-522) and is well known to those skilled in the art.Alternatively, intermediate 8a, in which FG means a functional group, for example trifluoroborate (FG=BF), can be used in a cross-coupling reaction (step a), applying a palladium catalyst, such as for example tetrakis(triphenylphosphine)-palladium(0), palladium(II) acetate or dichloro[1,1'-bis(diphenylphosphino)ferrocene]-palladium(II) DCM adduct, in a solvent such as toluene, THF, dioxane, water or a mixture thereof, in the presence of a suitable base, such as cesium carbonate or potassium phosphate, at a temperature between room temperature and the boiling point of the solvent or solvent mixture.

[0199] Alternatively, intermediate 2a can be reacted with intermediate 8a, in which FG represents a functional group such as stannane (FG is Sn(alkyl)3, where alkyl is optionally n-butyl or methyl), using a suitable catalyst and solvent, such as tetrakis(triphenylphosphine)-palladium(0), in DMF, at a temperature between room temperature and the boiling point of the solvent or solvent mixture, to give intermediate 4a (step a). Stille reactions of this type are well known in the art and have been described in literature, such as Org. React. 1997, 50, 1-652 and ACS Catal. 2015, 5, 3040-3053.

[0200] Furthermore, intermediate 2a can be reacted with intermediate 8a, in which FG represents a functional group such as zinc halide (FG = ZnHal and Hal, preferably Br or I), either commercially available or prepared by literature methods, using a suitable catalyst and solvent system, such as [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) and copper(I) iodide in DMA, or tetrakis(triphenylphosphine)palladium(0) in THF or DMF, at a temperature between room temperature and the boiling point of the solvent, to give intermediate 4a (Step a). This type of Negishi reaction is well known in the art and has been described in literature, such as Org. Lett., 2005, 7, 4871; ACS Catal. 2016, 6, 1540-1552; Acc. Chem. Res. 1982, 15, pp. 340-348. Alternatively, intermediate 10 may be prepared by first converting intermediate 2a, where X is, for example, iodide, to the corresponding zinc species by applying literature methods (e.g., reaction of 2a with Zn powder in the presence of chlorotrimethylsilane and 1,2-dibromoethane in a suitable solvent such as DMA), followed by coupling the zinc species with an aryl- or heteroaryl bromide- or iodide under the conditions described above.

[0201] Alternatively, intermediate 2a, in which X is preferably bromide, can be subjected to cross-electrophilic coupling with intermediate 8a, in which FG represents a functional group, for example, bromide (FG = Br), using a suitable photocatalyst such as nickel catalysts like [Ir{dF(CF)ppy}(dtbpy)]PF ([4,4'-bis(1,1-dimethylethyl)-2,2'-bipyridine-N,N']bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate), NiClglyme (dichloro(dimethoxyethane)nickel), 4,4'-di-tert-butyl-2,2'-dipyridyl, and tris(trimethylsilyl)silane, in the presence of a suitable base such as anhydrous sodium carbonate in a solvent such as DME, under irradiation with a 420 nm blue light lamp. This type of reaction is described in the literature, such as J. Am. Chem. Soc. 2016, 138, 8084 (step a).

[0202] Furthermore, intermediate 2a, where X is preferably iodide, can be subjected to Suzuki-Miyaura cross-coupling with arylboronic acid 8a (FG = B(OH)2) in the presence of rac-(1R,2R)-2-aminocyclohexan-1-ol and a suitable base such as sodium bis(trimethylsilyl)amide in a suitable solvent such as iPrOH, dioxane, THF, or DME, preferably iPrOH, at a temperature between room temperature and the boiling point of the solvent, using a suitable nickel catalyst such as nickel(II) iodide, optionally with microwave heating, to give intermediate 4a. This type of reaction has been described in the literature, for example, Chemistry Select. 2017, 2, 8841 (Step a).

[0203] Alternatively, intermediate 2a can be reacted with intermediate 8a (wherein FG represents a functional group such as an amine) at a temperature between room temperature and the boiling point of the solvent or solvent mixture, using a suitable catalyst and solvent, such as tris(dibenzylideneacetone)dipalladium(0) chloroform adduct and X-Phos or bis(diphenylphosphino)-1,1'-binaphthalene and palladium(II) acetate in tert-butanol or 1,4-dioxane, and a suitable base, such as CsCO or KOtBu, to give intermediate 4a (Step a). This type of Buchwald-Hartwig reaction is well known in the art and has been described in literature, such as Angewandte Chemie. 2019, 58, 17118-17129.

[0204] For example, intermediate 2a, in which X is preferably bromide or iodide, can be obtained commercially or by reaction with a suitable catalyst (e.g., dichloro[1,1'-bis(diphenylphosphino)-ferrocene]palladium(II) DCM adduct, tetrakis(triphenylphosphine)palladium(0) or palladium(II) acetate with triphenylphosphine) in a suitable solvent (e.g., dioxane, dimethoxyethane, water, toluene, DMF or mixtures thereof) and a suitable base (e.g., Na2CO3, NaHCO3, KF, K2CO3 or TEA) at a temperature between room temperature and the boiling point of the solvent or solvent mixture, either commercially available or as described, for example, in "Boronic Acids - Preparation and Applications in Organic Synthesis and

[0046] Reaction of intermediate 5a, where FG denotes a functional group, such as boronic acid (FG = B(OH)2) or boronic ester (FG = e.g., 4,4,5,5-tetramethyl-2-phenyl-1,3,2-dioxaborolane (pinacol) ester) and X = F, prepared using literature procedures such as those described in "Medicine" can give intermediate 6a (step c). This type of Suzuki reaction has been widely described in the literature (e.g., A. Suzuki, Pure Appl. Chem. 1991, 63, 419-422; A. Suzuki, N. Miyaura, Chem. Rev. 1995, 95, 2457-2483; A. Suzuki, J. Organomet. Chem. 1999, 576, 147-168; V. Polshettiwar et al., Chem. Sus. Chem. 2010, 3, 502-522) and is well known to those skilled in the art.

[0205] Intermediate 6a can be converted to FG=S under nucleophilic substitution conditions in a suitable solvent such as DMSO at temperatures between 0°C and 100°C. - Na + and intermediate 7a where R2 = Me to give compound 4a (step d).

[0206] Alternatively, the intermediate 4a thus obtained can be oxidized using a reactant such as m-chloroperbenzoic acid in a suitable solvent such as DCM at a temperature between 0° C. and 25° C. to give compound 4a.

[0207] Removal of the protecting group from intermediate 4a, where PG represents a protecting group such as tert-butyloxycarbonyl (BOC), can be carried out using methods well known and described in the art (see "Protective Groups in Organic Chemistry" T.W. Greene and P.G.M. Hutts, 5th Ed., 2014, John Wiley & Sons, New York), for example using TFA or hydrochloric acid in a solvent such as DCM, 1,4-dioxane or THF, preferably at room temperature, or 4-methylbenzenesulfonic acid hydrate in a solvent such as EtOAc, preferably at elevated temperature, to give intermediate 1a (step b).

[0208] In some embodiments, intermediate 1 is an intermediate of type 1b. 1 , R 2 , R 3 , R 4 Intermediate 1b, where A and B are as described herein, can be prepared by a variety of conditions, which can be exemplified by the general synthetic procedure outlined in Scheme 5. [ka] Scheme 5

[0209] Addition of an organometallic compound of type 3b, in which MX is, for example, Li, MgCl, MgBr, or MgI, to intermediate 4b, in which PG is a suitable protecting group, such as a Boc group, gives intermediate 5b (Step a). This type of reaction is well known in the art and has been described in the literature (J. Med. Chem. 1989, 32(1), 105; J. Med. Chem. 2014, 57(4), 1543; Bioorg. Med. Chem Lett. 2015, 25(13), 2720). If compound 3b (Grignard reagent) in which MX = MgHal and Hal is Cl, Br, or I is not commercially available, it can be prepared, for example, by reacting the corresponding aryl or heteroaryl halide 2b with magnesium in a suitable solvent, such as THF, at temperatures ranging from 0 °C to the boiling point of the solvent, optionally in the presence of a catalytic amount of iodine (Step d). Alternatively, a lithium halogen exchange reaction can be carried out with aryl or heteroaryl halide 2b using a solution of LiHMDS or n-BuLi, preferably n-BuLi, in a solvent such as THF, diethyl ether, n-pentane, n-hexane, or a mixture thereof, preferably THF, at a temperature ranging from −20° C. to −78° C., preferably at −78° C., to generate the corresponding lithiated aryl or heteroaryl intermediate (M=Li). The in situ prepared lithiated aryl or heteroaryl intermediate undergoes nucleophilic addition to a ketone of type 4b, where PG is a suitable protecting group such as a Boc group, in a solvent such as THF, preferably at a temperature of −78° C., to give the corresponding tertiary alcohol 5b (Step a).

[0210] Subsequent elimination of the tertiary hydroxy group in intermediate 5b, optionally with concomitant removal of an acid-labile protecting group (e.g., a Boc protecting group), using acidic conditions such as 4 M HCl in dioxane in a solvent such as MeOH, or preferably TFA in DCM, provides the corresponding olefin intermediate 6b (step b).

[0211] Heterogeneous catalytic hydrogenation of olefin 6b using a catalyst such as Pd(OH)2 or Pd / C, preferably Pd / C in THF, in a solvent such as THF, MeOH, EtOH, EtOAc or mixtures thereof, for example under atmospheric pressure of hydrogen, gives intermediates of type 1b (step c).

[0212] Intermediate 4b is commercially available and / or can be prepared analogously to methods described in the literature, such as Bioorg.Med.Chem.Lett. 2011, 21(18), 5191, WO2012 / 155199, WO2016 / 180536, Bioorg.Med.Chem.Lett. 2008, 18(18), 5087, WO2007 / 117557, J.Am.Chem.Soc. 2017, 139(33), 11353, J.Med.Chem. 2017, 60(13), 5507.

[0213] In some embodiments, intermediate 1 is an intermediate of type 1c. 1 , R 2 , R 3 Intermediate 1c, where A and B are as described herein, can be prepared by methods well known in the art and as exemplified by the general synthetic procedure outlined in Scheme 6. [ka] Scheme 6

[0214] Ketone 2c, where PG is a suitable protecting group and is either commercially available or prepared by methods known in the art, can be subjected to a Wittig reaction with alkylidene triphenylphosphorane of type 3c in a suitable solvent such as THF, methyl-THF, or DMSO to provide intermediate 5c (Step a). The corresponding phosphonium salt of phosphorane 3c can be formed by treatment with a suitable base such as BuLi, NaH, or KOtBu in a suitable solvent such as THF, dioxane, or methyl-THF, and can be isolated or used in situ. Similarly, phosphonium salts are readily available from aryl / heteroaryl / heterocycle-substituted alkyl halides (halides are Cl, Br, and iodine) and triphenylphosphine in a suitable solvent such as toluene. Heating may be used to accelerate the reaction or drive it to completion (e.g., H.J. Cristau, F. Plenat in PATAI'S Chemistry of Functional Groups, Editor(s): Frank R. Hartley, August 2006, Series Editor(s): Prof. Saul Patai).

[0215] Alternatively, intermediate 5c can be obtained using a Horner-Wadsworth-Emmons (HWE) reaction with ketone 2c and phosphonate 4c, followed by R a is alkyl, e.g., methyl or ethyl. Phosphonate 4c is α-metallated in situ using a suitable base and solvent, such as NaH, nBuLi, or KOtBu in THF (step a). Phosphonate 4c is readily prepared, for example, using the Arbuzov reaction by alkylating aryl / heteroaryl / heterocyclic halides (halides are Cl, Br, and iodine) with commercially available trialkyl phosphites (e.g., Chem. Rev. 1984, 84, 577).

[0216] Both types of olefination reactions have been widely described in the literature (e.g. Current Org. Chem. 2015, 19(9), page 744; Chem. Rev. 1989, 89(4), 863; Org. React. 1977, 25, 73; Liebigs Ann. / Recueil 1997, 1283; Acc. Chem. Res. 1983, 16, 411).

[0217] Reduction of the double bond in intermediate 5c with, for example, hydrogen in the presence of a suitable catalyst, such as palladium on charcoal, in a suitable solvent or solvent mixture, such as EtOAc, MeOH, or AcOH, gives compound 6c (step b).

[0218] Removal of the protecting group from intermediate 6c applying methods known in the art (e.g., Boc group using TFA in DCM or 4 M HCl in dioxane at temperatures between 0° C. and room temperature, Cbz group using hydrogen in the presence of a suitable catalyst such as Pd on charcoal or Pd(OH) in a suitable solvent such as MeOH, EtOH, EtOAc, or mixtures thereof, and groups such as those described in, for example, "Protective Groups in Organic Chemistry", T.W. Greene and P.G.M. Buts, 4th Edition (2006), Wiley, New York) gives intermediate 1c (step c).

[0219] In some embodiments, intermediate 1 is an intermediate of type 1d. 1 , R 2 , R 3 Intermediate 1d, where A and B are as described herein, can be prepared by methods well known in the art and as exemplified by the general synthetic procedure outlined in Scheme 7. [ka] Scheme 7

[0220] Alcohols of type 2d can be reacted with intermediate 3d, where PG is a suitable protecting group such as Cbz, Boc, or Bn, to afford intermediate 4d (step a) using an appropriate phosphine, such as triphenylphosphine, and a dialkyl azodicarboxylate, such as DEAD or DIAD, in a suitable solvent, such as THF (Mitsunobu reaction). This type of Mitsunobu reaction has been widely described in the literature (e.g., Org. Chem. Front. 2015, 2, 739; Chem. Rev. 2009, 109(6), 2551).

[0221] Alternatively, intermediate 4d may be prepared from alcohol 2d, which can be alkylated with compound 5d, where LG is a suitable leaving group, such as chlorine, bromine, iodine, OSO2 alkyl (e.g., methanesulfonic acid), OSO2 fluoroalkyl (e.g., trifluoromethanesulfonic acid), or OSO2 aryl (e.g., p-toluenesulfonic acid), using a suitable base such as NaH or Cs2CO3 in a suitable solvent such as DMF or ACN at a temperature between 0°C and the boiling point of the solvent (step c).

[0222] Furthermore, intermediate 4d can be synthesized via alkylation of alcohols of type 3d with compounds 6d under the conditions described in step c (step d).

[0223] Removal of the protecting group from intermediate 4d by applying literature methods and methods described, for example, in Scheme 4, step b below, gives intermediate 1d (step b).

[0224] In some embodiments, intermediate 1 is an intermediate of type 1e. 1 , R 2 , R 3 Intermediate 1e, where A and B are as described herein, can be prepared by a variety of conditions, which can be exemplified by the general synthetic procedure outlined in Scheme 8. [ka] Scheme 8

[0225] Alcohols of type 2d can be reacted with intermediate 3e, where PG is a suitable protecting group such as Cbz, Boc, or Bn, to give intermediate 2e (step a) using an appropriate phosphine, such as triphenylphosphine, and a dialkyl azodicarboxylate, such as DEAD or DIAD, in a suitable solvent, such as THF, DCM, or ACN, to give intermediate 2e (step a). Mitsunobu reactions of this type have been widely described in the literature (e.g., Org. Chem. Front. 2015, 2, 739; Chem. Rev. 2009, 109(6), 2551).

[0226] Removal of the protecting group from intermediate 2e by applying literature methods and methods described, for example, in Scheme 4, step b below, gives intermediate 1e (step b).

[0227] Alternatively, intermediate 2e may be prepared from alcohol 2d, which can be alkylated with compound 4e, where LG is a suitable leaving group, such as chlorine, bromine, iodine, OSO2 alkyl (e.g., methanesulfonic acid), OSO2 fluoroalkyl (e.g., trifluoromethanesulfonic acid), or OSO2 aryl (e.g., p-toluenesulfonic acid), using a suitable base such as Cs2CO3, Huenig's base, or NaH in a suitable solvent, such as DMF, at a temperature between 0°C and the boiling point of the solvent (step c).

[0228] In some embodiments, intermediate 1 is an intermediate of type 1f. 1 , R 2 , R 3 Intermediate 1f, where A and B are as described herein, can be prepared by methods known in the art and as exemplified by the general synthetic procedure outlined in Scheme 9. [ka] Scheme 9

[0229] Intermediate 3f can be prepared from alcohol 3d, which is commercially available or prepared by methods known to those skilled in the art, and where LG is a suitable leaving group such as chlorine, bromine, iodine, OSO2 alkyl (e.g., methanesulfonate), OSO2 fluoroalkyl (e.g., trifluoromethanesulfonate), or OSO2 aryl (e.g., p-toluenesulfonate), by alkylation with a suitable base, such as sodium hydride, Huenig's base, or potassium tert-butoxide, in a suitable solvent (e.g., DMF or THF) at a temperature between 0°C and the boiling point of the solvent (Step a).

[0230] Removal of the protecting groups from intermediate 3f by methods known in the art (e.g., Boc group using TFA in DCM at temperatures between 0° C. and room temperature, Cbz group using hydrogen in the presence of a suitable catalyst such as Pd on charcoal or Pd(OH) in a suitable solvent such as MeOH, EtOH, EtOAc, or a mixture thereof, and groups such as those described in, for example, "Protective Groups in Organic Chemistry" by T.W. Greene and P.G.M. Buts, 4th Ed., 2006, Wiley NY) gives intermediate 1f (step b).

[0231] In some embodiments, intermediate 1 is an intermediate of type 1g. 1 , R 2 , R 3 Intermediates of type 1g, where A and B are as described herein, can be prepared by methods well known to those skilled in the art, as exemplified by the general synthetic procedure outlined in Scheme 9. [ka] Scheme 9

[0232] Aldehydes 2g, commercially available or prepared by methods known in the art, can be subjected to a Wittig or Horner-Wadsworth-Emmons (HWE) reaction using alkylidene triphenylphosphoranes of type 3c and phosphonates 4c, respectively, using conditions described, for example, in Scheme 6, step a, to afford intermediates 3g (step a).

[0233] Reduction of the double bond in intermediate 3g applying literature conditions or conditions described in Scheme 5, step c or Scheme 6, step b gives compound 4g (step b).

[0234] Removal of the protecting group from intermediate 4g, as outlined in Scheme 4, step b, applying methods known in the art, gives intermediate 1g (step c).

[0235] In another embodiment, intermediate 1 is an intermediate of type 1h. 1 , R 2 , R 3 Intermediates of type 1h, where A and B are as described herein, can be prepared by methods well known in the art, as exemplified by the general synthetic procedure outlined in Scheme 10. [ka] Scheme 10

[0236] Alkyne 2h, where PG represents a suitable protecting group, e.g., Boc, Cbz, or Bn, either commercially available or prepared by methods known in the art, can be subjected to Sonogashira reaction (e.g., Chem. Soc. Rev. 2011, 40, 5084) with aryl or heteroaryl halide 3h, where LG is preferably Br, I, or OTf, to give intermediate 9 (Step a) using a suitable catalyst, e.g., Pd(OAc) / PPh, Pd(PPh), preferably PdCh(PPh), in the presence of Cui and a suitable base, e.g., KCO, CSO, DIPEA, or preferably TEA, and a suitable solvent, e.g., THF, DMSO, DMF, NMP, CHCN, or dioxane, preferably THF, at a temperature ranging from room temperature to 100 °C, preferably about 65 °C.

[0237] Removal of the protecting groups from intermediate 3h can be carried out by methods known in the art, for example, the Boc group using TFA in DCM or 4M HCl in dioxane at temperatures between 0° C. and room temperature, the Cbz group using hydrogen over charcoal in a suitable solvent such as MeOH, EtOH, EtOAc or mixtures thereof in the presence of a suitable catalyst, for example, Pd or Pd(OH) 2 , and methods described, for example, in “Protective Groups in Organic Chemistry” by T.W. Greene and P.G.M. Butts, 4th Ed., 2006, Wiley NY), to give intermediate 1h (step b).

[0238] In some embodiments, intermediate 3 is an intermediate of type 3i. 1 , R 2 , R 3 Intermediate 3i, where A and B are as described herein, can be prepared by methods known in the art and as exemplified by the general synthetic procedure outlined in Scheme 11. [ka]

[0239] Intermediate 3i can be prepared from alcohol 5i, which is commercially available or prepared by methods known to those skilled in the art, and where PG is a suitable protecting group such as methyl, ethyl, or tert-butyl, by alkylation with compound 4i, where FG is a suitable leaving group such as chlorine, bromine, iodine, OSO2 alkyl (e.g., methanesulfonate), OSO2 fluoroalkyl (e.g., trifluoromethanesulfonate), or OSO2 aryl (e.g., p-toluenesulfonate), using a suitable base, such as sodium hydride, Huenig's base, or potassium tert-butoxide, in a suitable solvent (e.g., DMF or THF) at a temperature between 0°C and the boiling point of the solvent (Step a).

[0240] Intermediate 3i can be prepared from aldehydes or ketones 6i, either commercially available or prepared by methods known to those skilled in the art, in which PG is a suitable protecting group such as methyl, ethyl, or tert-butyl, by reductive etherification with compound 4i, in which FG is a hyroxy group, using a suitable reagent such as EtSiH and bismuth(III) chloride in a suitable solvent (e.g., DCM) at a temperature between 0°C and the boiling point of the solvent (Step b), or using conditions described in the literature (e.g., S. Hatakeyama, Tetrahedron Letters, Vol. 35, No. 25, pp. 4367-4370, 1994).

[0241] Removal of the protecting groups from intermediate 3i applying methods known in the art (e.g., methyl group using LiOH or NaOH in a mixture of water and, for example, THF or 1,4-dioxane at a temperature between 0° C. and room temperature, or tert-butyl group using a suitable acid such as HCl or TFA in a suitable solvent such as AcOH, DCM or a mixture thereof, as described, for example, in "Protective Groups in Organic Chemistry", T.W. Greene and P.G.M. Buts, 4th Ed., 2006, Wiley NY) gives intermediate 3a (step c).

[0242] In one aspect, the present invention provides a method of making a compound of formula (IA) or (IB) described herein, comprising: (a) an amine of formula 2, wherein p, q and R 4 are as described herein) [ka] with carboxylic acid 3a (wherein L, A, B, and R 1 ~R 3 are as described herein) [ka] in the presence of a coupling reagent such as CDI, DCC, HATU, HBTU, HOBT, TBTU, T3P or Mukaiyama reagent, and optionally in the presence of a base such as TEA, DIPEA (Huenig base) or DMAP, to give a compound of formula (IB) (wherein A, B, L, p, q, and R 1 ~R 4 is as defined herein) [ka] ;or (b) an amine of formula 2, wherein p, q and R 4 are as described herein) [ka] with carboxylic acid chloride 3b (wherein L, A, B, and R 1 ~R 3 are as described herein) [ka] in the presence of a base such as TEA, Huenig's base, pyridine, DMAP, or lithium bis(trimethylsilyl)amide to give a compound of formula (IB), 1 ~R 4 is as defined herein); or (c) a first amine of Formula 1, wherein A, B, L, and R 1 ~R 3 are as described herein) [ka] with a second amine 2, wherein X, Y, and Z are as described herein. [ka] in the presence of a base such as sodium bicarbonate and a urea-forming reagent such as bis(trichloromethyl)carbonate, phosgene, trichloromethyl chloroformate, (4-nitrophenyl)carbonate, or 1,1′-carbonyldiimidazole, A compound of formula (IA) 1 ~R 4 is as defined herein) [ka] forming a

[0243] In one aspect, the present invention provides a compound of formula (I) as described herein when prepared according to any one of the methods described herein.

[0244] MAGL inhibitory activity The compounds of the invention are MAGL inhibitors. Thus, in one aspect, the invention provides the use of a compound of formula (I) as described herein for inhibiting MAGL in a mammal.

[0245] In a further aspect, the present invention provides a compound of formula (I) as described herein for use in a method of inhibiting MAGL in a mammal.

[0246] In a further aspect, the present invention provides the use of a compound of formula (I) as described herein for the preparation of a medicament for inhibiting MAGL in a mammal.

[0247] In a further aspect, the present invention provides a method for inhibiting MAGL in a mammal, comprising administering to the mammal an effective amount of a compound of formula (I) as described herein.

[0248] Compounds were profiled for MAGL inhibitory activity by determining the enzyme activity following the hydrolysis of the natural substrate, 2-arachidonoylglycerol, to generate arachidonic acid. Mass spectrometry may then be performed. This assay is hereinafter abbreviated as "2-AG assay."

[0249] The 2-AG assay was performed in a 384-well assay plate (PP, Greiner, catalog no. 784201) in a total volume of 20 μL. Compound dilutions were made in 100% DMSO (VWR Chemicals 23500.297) in 3-fold dilution steps in the polypropylene plate to give a final concentration range in the assay of 12.5 μM to 0.8 pM. 0.25 μL of compound dilution (100% DMSO) was added to 9 μL of MAGL in assay buffer (50 mM TRIS (GIBCO, 15567-027), 1 mM EDTA (Fluka, 03690-100ml), 0.01% (vol / vol) Tween). After shaking, the plate was incubated at room temperature for 15 minutes. 10 μL of 2-arachidonoylglycerol in assay buffer was added to initiate the reaction. The final concentrations in the assay were 50 pM MAGL and 8 μM 2-arachidonoylglycerol. After shaking and incubation at room temperature for 30 min, the reaction was quenched by adding 40 μL of acetonitrile containing 4 μM d8-arachidonic acid. The amount of arachidonic acid was monitored using an online SPE system (Agilent Rapidfire) coupled to a triple quadrupole mass spectrometer (Agilent 6460). A C18 SPE cartridge (G9205A) was used in an acetonitrile / water liquid setup. The mass spectrometer was operated in negative electrospray mode, following the mass transitions of 303.1 → 259.1 for arachidonic acid and 311.1 → 267.0 for d8-arachidonic acid. Compound activity was calculated based on the intensity ratio (arachidonic acid / d8-arachidonic acid). [Table 1] TIFF2025525350000109.tif246170 TIFF2025525350000110.tif246170 TIFF2025525350000111.tif245170 TIFF2025525350000112.tif245170 TIFF2025525350000113.tif245170 TIFF2025525350000114.tif246170 TIFF2025525350000115.tif245170 TIFF2025525350000116.tif246170 TIFF2025525350000117.tif246170 TIFF2025525350000118.tif246170 TIFF2025525350000119.tif246170 TIFF2025525350000120.tif246170 TIFF2025525350000121.tif246170 TIFF2025525350000122.tif207170

[0250] In one aspect, the present invention provides compounds of formula (I), and pharmaceutically acceptable salts or esters thereof as described herein, which compounds of formula (I), and pharmaceutically acceptable salts or esters thereof, have an IC for MAGL inhibition as measured in the MAGL assay described herein. 50 is less than 25 μM, preferably less than 10 μM, more preferably less than 5 μM.

[0251] In one embodiment, the compounds of formula (I) described herein and their pharmaceutically acceptable salts or esters have an IC 50 (MAGL inhibition) values range from 0.000001 μM to 25 μM, and certain compounds have IC 50 values between 0.000005 μM and 10 μM, and more specific compounds have IC 50 The value is between 0.00005 μM and 5 μM.

[0252] MAGL NanoBRET™ Target Engagement Assay Compounds were profiled using a novel cellular MAGL NanoBRET™ target engagement assay, which measures the apparent affinity of test compounds by competitive displacement of a Roche-developed tracer reversibly bound to an intracellular NanoLuc® luciferase-MAGL fusion protein.

[0253] The tracer developed by Roche is described in WO2021058443 (Example 21) and has the following structure: [ka]

[0254] A stable HEK293A cell line expressing NanoLuc_MAGL was established at Roche and designated HEK293A_NanoLuc_MAGL clone #43. A fixed concentration of tracer was added to cells expressing the NanoLuc®_MAGL fusion protein to generate a BRET reporter complex. Introduction of a competitor compound resulted in a dose-dependent decrease in NanoBRET™ energy transfer, allowing quantification of the intracellular affinity of the target protein for the test compound.

[0255] HEK293A_NanoLuc_MAGL clone #43 cells were cultured in DMEM (Gibco 31966) containing 10% FBS and 800 μg / ml G418. NanoBRET assays were performed by seeding 5000 cells / well into Costar low-volume white 384-well plates in assay buffer (1% FBS in HBSS) followed by the addition of serial dilutions of tracer and test compound at a final concentration of 50 nM. After a 2-hour incubation, Nanoluciferase substrate and extracellular inhibitors were added according to the manufacturer's protocol (Promega, #N2520), and NanoBRET signaling was quantified using a Paradigm (Molecular Devices) instrument. [Table 2]

[0256] In one aspect, the present invention provides compounds of formula (I), and pharmaceutically acceptable salts or esters thereof as described herein, which compounds of formula (I), and pharmaceutically acceptable salts or esters thereof, have an IC for NanoBRET target engagement as measured in the MAGL assay described herein. 50 is less than 25 μM, preferably less than 10 μM, more preferably less than 5 μM.

[0257] In one embodiment, the compounds of formula (I) described herein and their pharmaceutically acceptable salts or esters have an IC 50 (MAGL inhibition) values ranged from 0.0001 μM to 25 μM, and certain compounds exhibited IC 50 values between 0.0005 μM and 10 μM, and furthermore, certain compounds have IC 50 The values are between 0.001 μM and 5 μM.

[0258] Uses of the Compounds of the Invention In one aspect, the present invention provides a compound of formula (I), as described herein, or a pharmaceutically acceptable salt thereof, for use as a therapeutically active substance.

[0259] In a further aspect, the present invention provides the use of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for the treatment or prevention of neuroinflammation, neurodegenerative diseases, pain, cancer, psychiatric disorders and / or inflammatory bowel disease in a mammal.

[0260] In one embodiment, the present invention provides the use of a compound of formula (I), as described herein, or a pharmaceutically acceptable salt thereof, for the treatment or prevention of a neuroinflammatory and / or neurodegenerative disease in a mammal.

[0261] In one embodiment, the present invention provides the use of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for the treatment or prevention of a neurodegenerative disease in a mammal.

[0262] In one embodiment, the present invention provides the use of a compound of formula (I), as described herein, or a pharmaceutically acceptable salt thereof, for the treatment or prevention of cancer in a mammal.

[0263] In one embodiment, the present invention provides the use of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for the treatment or prevention of inflammatory bowel disease in a mammal.

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

[0265] In one aspect, the present invention provides the use of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for the treatment or prevention of multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, anxiety, migraine, depression, hepatocellular carcinoma, colon carcinogenesis, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, pain-associated spasticity, abdominal pain, abdominal pain associated with irritable bowel syndrome, and / or visceral pain in a mammal.

[0266] In a preferred embodiment, the present invention provides the use of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for the treatment or prevention of multiple sclerosis, Alzheimer's disease and / or Parkinson's disease in a mammal.

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

[0268] In one aspect, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof for use in the treatment or prevention of neuroinflammation, neurodegenerative diseases, pain, cancer, psychiatric disorders and / or inflammatory bowel disease in a mammal.

[0269] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a neuroinflammatory and / or neurodegenerative disease in a mammal.

[0270] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of cancer in a mammal.

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

[0272] In one embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of inflammatory bowel disease in a mammal.

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

[0274] In one aspect, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof for use in the treatment or prevention of multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, anxiety, migraine, depression, hepatocellular carcinoma, colon carcinogenesis, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, pain-associated spasticity, abdominal pain, abdominal pain associated with irritable bowel syndrome, and / or visceral pain in a mammal.

[0275] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of multiple sclerosis, Alzheimer's disease and / or Parkinson's disease in a mammal.

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

[0277] In one aspect, the present invention provides the use of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment or prevention of neuroinflammation, neurodegenerative diseases, pain, cancer, psychiatric disorders and / or inflammatory bowel disease in a mammal.

[0278] In one embodiment, the present invention provides the use of a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof for the preparation of a medicament for the treatment or prevention of a neuroinflammatory and / or neurodegenerative disease in a mammal.

[0279] In one embodiment, the present invention provides the use of a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof for the preparation of a medicament for the treatment or prevention of a neurodegenerative disease in a mammal.

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

[0281] In one embodiment, the present invention provides the use of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment or prevention of inflammatory bowel disease in a mammal.

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

[0283] In a further aspect, the present invention provides the use of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment or prevention of multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, anxiety, migraine, depression, hepatocellular carcinoma, colon carcinogenesis, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, pain-associated spasticity, abdominal pain, abdominal pain associated with irritable bowel syndrome, and / or visceral pain in a mammal.

[0284] In a preferred embodiment, the present invention provides the use of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment or prevention of multiple sclerosis, Alzheimer's disease and / or Parkinson's disease in a mammal.

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

[0286] In one aspect, the present invention provides a method for the treatment or prevention of neuroinflammation, neurodegenerative diseases, pain, cancer, psychiatric disorders and / or inflammatory bowel disease in a mammal, the method comprising administering to the mammal an effective amount of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof.

[0287] In one embodiment, the present invention provides a method for the treatment or prevention of a neuroinflammatory and / or neurodegenerative disease in a mammal, the method comprising administering to the mammal an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof, as described herein.

[0288] In one embodiment, the present invention provides a method for the treatment or prevention of a neurodegenerative disease in a mammal, the method comprising administering to the mammal an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof, as described herein.

[0289] In one embodiment, the present invention provides a method for the treatment or prevention of cancer in a mammal, the method comprising administering to the mammal an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof, as described herein.

[0290] In one embodiment, the present invention provides a method for the treatment or prevention of inflammatory bowel disease in a mammal, the method comprising administering to the mammal an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof, as described herein.

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

[0292] In a further aspect, the present invention provides a method for the treatment or prevention of multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, anxiety, migraine, depression, hepatocellular carcinoma, colon carcinogenesis, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, pain-associated spasticity, abdominal pain, abdominal pain associated with irritable bowel syndrome, and / or visceral pain in a mammal, comprising administering to the mammal an effective amount of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof.

[0293] In a preferred embodiment, the present invention provides a method for the treatment or prevention of multiple sclerosis, Alzheimer's disease and / or Parkinson's disease in a mammal, comprising administering to the mammal an effective amount of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof.

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

[0295] Pharmaceutical Compositions and Administration In one aspect, the present invention provides a pharmaceutical composition comprising a compound of formula (I) described herein and a therapeutically inert carrier.

[0296] In one embodiment, the present invention provides the pharmaceutical compositions disclosed in Examples 866 and 867.

[0297] The compounds of formula (I) and their pharmaceutically acceptable salts and esters can be used as pharmaceuticals (for example, in the form of pharmaceutical preparations).The pharmaceutical preparations can be administered to the body orally (for example, in the form of tablets, coated tablets, sugar-coated tablets, hard gelatin capsules and soft gelatin capsules, solutions, emulsions or suspensions), nasally (for example, in the form of nasal drops), or rectally (for example, in the form of suppositories).However, administration can also be carried out parenterally, such as intramuscularly or intravenously (for example, in the form of injections).

[0298] The compound of formula (I) and its pharmaceutically acceptable salts and esters can be processed with pharmaceutically inert inorganic or organic adjuvants for the preparation of tablets, coated tablets, sugar-coated tablets, and hard gelatin capsules. Lactose, corn starch or its derivatives, talc, stearic acid, or its salts, etc., can be used as adjuvants for tablets, sugar-coated tablets, and hard gelatin capsules, for example.

[0299] Suitable adjuvants for soft gelatin capsules are, for example, vegetable oils, waxes, fats, semisolid substances, and liquid polyols.

[0300] Suitable adjuvants for the production of solutions and syrups are, by way of example, water, polyols, saccharose, invert sugar, glucose etc.

[0301] Suitable adjuvants for injection solutions are, for example, water, alcohols, polyols, glycerol, vegetable oils and the like.

[0302] Suitable adjuvants for suppositories are, for example, natural or hardened oils, waxes, fats, semi-solid or liquid polyols etc.

[0303] In addition, pharmaceutical preparations may contain preservatives, solubilizers, viscosity-increasing substances, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavoring agents, salts for varying osmotic pressure, buffers, masking agents, or antioxidants. They may also contain still other therapeutically valuable substances.

[0304] Dosage can vary widely and will of course be adapted to the individual requirements of each particular case.Generally, for oral administration, a daily dosage of about 0.1 mg to 20 mg / kg body weight, preferably about 0.5 mg to 4 mg / kg body weight (for example, about 300 mg / person) will be appropriate, preferably divided into 1 to 3 individual doses, for example, of the same amount.However, it is clear that the upper limit given herein can be exceeded if indicated. [Example]

[0305] The present invention will be more fully understood by reference to the following examples, which should not, however, be construed as limiting the scope of the claims to the examples.

[0306] Where preparations are obtained as mixtures of enantiomers, the pure enantiomers may be separated by the methods described herein or by methods known to those skilled in the art, such as chiral chromatography (e.g., chiral SFC) or crystallization.

[0307] Unless otherwise noted, all reactions and intermediates were prepared under an argon atmosphere.

[0308] Separation method HPLC method GN Gemini NX, 12 nm, 5 μm, 100 × 30 mm, 15 min gradient, ACN / water + 0.1% FA HPLC method YMC YMC-Triart C18, 12 nm, 5 μm, 100 × 30 mm, gradient, ACN / water + 0.1% FA Chiral Separation Methods HPLC method OD1 Chiralcel OD, normal phase (isocratic): 80% heptane; 20% ethanol + NH₄Oac HPLC method OD2 Chiralcel OD, normal phase (isocratic): 60% heptane; 40% ethanol + NH₄Oac HPLC method AD Chiralpak-AD, normal phase (isocratic): 60% heptane; 40% ethanol + NH₄Oac HPLC method AD1 Chiralpak-AD, normal phase (isocratic): 70% heptane; 30% ethanol + NH₄Oac HPLC method NR Reprosil Chiral NR, normal phase (isocratic): 60% heptane; 40% ethanol + NH₄Oac SFC method AY (AY-H, 12nm, 5μm, 250 x 4.6mm column), eluent: 30% MeOH in supercritical CO2 SFC method ADH (AD-H, 12nm, 5μm, 250×4.6mm), Eluent: 40% MeOH in supercritical CO2 SFC method ADH1 (AD-H, 12nm, 5μm, 250×4.6mm), Eluent: 20% MeOH in supercritical CO2 SFC method ADH2 (AD-H, 12 nm, 5 μm, 250 × 4.6 mm), eluent: 30% IPA (0.1% NH3·H2O) in supercritical fluid CO2 SFC method ADH3 (AD-H, 12 nm, 5 μm, 250 × 4.6 mm), eluent: 40% MeOH (0.1% NH3·H2O) in supercritical CO2 SFC Method IC (IC, 12nm, 5μm, 250×20mm), eluent: 25% EtOH in supercritical CO2 SFC Method IC1 (IC, 12nm, 5μm, 250×20mm), eluent: 35% EtOH in supercritical CO2 SFC Method IA IA, 12 nm, 5 μm, 250 × 20 mm, 20% EtOH in supercritical CO2 SFC Method IG (IG, 12 nm, 5 μm, 250 × 20 mm), eluent: 40% MeOH (0.1% NH 3 · H 2 O) in supercritical CO 2 SFC Method IH (1H, 5μm, 250×20mm), eluent: 35% MeOH in supercritical CO2 SFC Method OJH OJ-H, 12 nm, 5 μm, 250 × 20 mm. 15% EtOH in supercritical CO2 SFC method OJH1 OJ-H, 12 nm, 5 μm, 250 × 20 mm. 20% EtOH in supercritical CO2 SFC method OJH2 OJ-H, 12nm, 5μm, 250×20mm. 25% IPA in supercritical CO2 SFC method ODH OD-H, 12nm, 5μm, 250×4,6mm. 20~40% EtOH in supercritical CO2 SFC method ODH1 OD-H, 5nm, 5μm, 250×20mm. 30% MeOH in supercritical CO2 SFC Method OD Chiralcel OD, 250mm*30mm, 10um, 40% IPA (0.1% NH3·H2O) in supercritical CO2 SFC Method OD1 Chiralcel OD, 250mm*30mm, 10um, 55% IPA (0.1% NH3·H2O) in supercritical CO2 SFC method OD3 Chiralcel OD, 250mm*30mm, 10um, 55% EtOH (0.1% NH3·H2O) in supercritical CO2 SFC method OD4 Chiralcel OD, 250mm*30mm, 10um, 50% IPA (0.1% NH3·H2O) in supercritical CO2 SFC method OD5 Chiralcel OD, 250mm*30mm, 10um, 45% MeOH (0.1% NH3·H2O) in supercritical CO2 SFC Method AD Chiralpak AD, 250mm*30mm, 10um, 40% (IPA / ACN 4 / 1) in supercritical CO2 (0.1% NH3·H2O) SFC Method AD1 Chiralpak AD, 250mm*30mm, 10um, 50% (IPA / ACN 4 / 1) in supercritical CO2 (0.1% NH3·H2O) SFC Method AD2 Chiralpak AD, 250mm*30mm, 10um, 55% EtOH (0.1% NH3·H2O) in supercritical CO2 SFC Method AD3 Chiralpak AD, 250mm*30mm, 10um, 45% (IPA / ACN 4 / 1) in supercritical CO2 (0.1% NH3·H2O) SFC Method AD4 Chiralpak AD, 250mm*30mm, 10um, 30% EtOH in supercritical CO2 SFC Method AD5 Chiralpak AD, 250mm*30mm, 10um, 60% (MeOH / ACN 3 / 1) (0.1% NH3·H2O) in supercritical CO2 SFC Method AD6 Chiralpak AD, 250mm*30mm, 10um, 30% MeOH (0.1% NH3·H2O) in supercritical CO2 SFC method AD7 Chiralpak AD, 250mm*30mm, 10um, 50% MeOH (0.1% NH3·H2O) in supercritical CO2 SFC method CE Cellulose-4 20 x 350 mm 5 um, 35% MeOH (0.2% DEA) in supercritical CO2

[0309] Example 1 [3-[[2-Fluoro-6-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone [ka] To an ice-cooled suspension of bis(trichloromethyl)carbonate (80 mg, 270 μmol, CAS RN 32315-10-9) and NaHCO (118 mg, 1.4 mmol) in DCM (1.5 mL) was added a solution of 3-((2-fluoro-6-(trifluoromethyl)benzyl)oxy)azetidine hydrochloride (100 mg, 350 μmol, CAS RN 1121613-07-7) in DCM (1.5 mL), and the mixture was stirred at room temperature overnight. To the suspension was added 5-(pyrrolidin-3-yl)-1H-pyrazole dihydrochloride (48 mg, 228 μmol, CAS RN 2173135-18-5) and DIPEA (313 μL, 1.79 mmol). The suspension was stirred at room temperature for 3.5 hours. The reaction mixture was poured onto water and DCM, and the layers were separated. The aqueous layer was extracted three times with DCM. The organic layer was dried over MgSO4, filtered and evaporated. The compound was purified using HPLC method YMC to give the desired compound as a colorless gum (25.8 mg; 17.9%). MS (ESI): m / z = 413.3 [M + H] + .

[0310] Unless otherwise indicated, the following examples were synthesized similarly to the synthesis described for Example 1, using each appropriate building block. [Table 3] TIFF2025525350000127.tif199170 TIFF2025525350000128.tif214170 TIFF2025525350000129.tif230170 TIFF2025525350000130.tif215170 TIFF2025525350000131.tif200170

[0311] Example 4 (+)- or (-)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone and Example 5 (-)- or (+)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone [ka] The racemate [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone (136 mg, 0.33 mmol, Example 1) was separated by HPLC method OD1 to give the desired product 4 (first elution) as a yellow oil (47 mg, 15.4%). MS (ESI): m / z = 413.3 [M + H] + and the desired product 5 (second elution) was obtained as a yellow oil (37 mg, 14.6%). MS (ESI): m / z = 413.3 [M+H] + .

[0312] Unless otherwise indicated, the following examples were isolated similarly to the syntheses described for Examples 4 and 5, using the appropriate starting materials, respectively. [Table 4] TIFF2025525350000134.tif194170 TIFF2025525350000135.tif215170 TIFF2025525350000136.tif251170 TIFF2025525350000137.tif204170 TIFF2025525350000138.tif209170 TIFF2025525350000139.tif198170 TIFF2025525350000140.tif219170 TIFF2025525350000141.tif227170 TIFF2025525350000142.tif250170 TIFF2025525350000143.tif241170 TIFF2025525350000144.tif213170 TIFF2025525350000145.tif214170 TIFF2025525350000146.tif214170 TIFF2025525350000147.tif244170 TIFF2025525350000148.tif229170 TIFF2025525350000149.tif229170 TIFF2025525350000150.tif209170 TIFF2025525350000151.tif251170 TIFF2025525350000152.tif207170 TIFF2025525350000153.tif212170 TIFF2025525350000154.tif138170

[0313] Example 6 [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(4-methyl-1H-pyrazol-5-yl)azetidin-1-yl]methanone [ka] To a solution of 5-(azetidin-3-yl)-4-methyl-1H-pyrazole 2,2,2-trifluoroacetic acid (38 mg, 151 μmol, CAS RN 1361115-19-6) in DCM (1 mL) was added DIPEA (79 μL, 151 μmol), followed by the addition of di(1H-1,2,4-triazol-1-yl)methanone (23.6 mg, 144 μmol) in one portion. The mixture was stirred at room temperature for 1 hour. 3-((2-fluoro-4-(trifluoromethyl)benzyl)oxy)azetidine 4-methylbenzenesulfonic acid (CAS RN 2135785-94-1) was added in one portion, and the clear solution was stirred at 50 °C overnight. The reaction mixture was completely evaporated. The product was purified by HPLC method GN (unless otherwise stated) to give the desired compound as a colorless amorphous (0.007 g; 11.2%). MS (ESI): m / z = 413.2 [M+H] + .

[0314] Unless otherwise indicated, the following examples were synthesized using the appropriate building blocks, similar to the synthesis described for Example 6. Reactions were carried out in DCM, DMF, or MeCN as solvents at temperatures between 50°C and 80°C. [Table 5] TIFF2025525350000157.tif202170 TIFF2025525350000158.tif216170 TIFF2025525350000159.tif206170 TIFF2025525350000160.tif191170 TIFF2025525350000161.tif202170 TIFF2025525350000162.tif193170 TIFF2025525350000163.tif206170 TIFF2025525350000164.tif211170 TIFF2025525350000165.tif212170 TIFF2025525350000166.tif186170 TIFF2025525350000167.tif196170 TIFF2025525350000168.tif206170 TIFF2025525350000169.tif191170 TIFF2025525350000170.tif212170 TIFF2025525350000171.tif196170 TIFF2025525350000172.tif206170 TIFF2025525350000173.tif198170 TIFF2025525350000174.tif208170 TIFF2025525350000175.tif211170 TIFF2025525350000176.tif190170 TIFF2025525350000177.tif226170 TIFF2025525350000178.tif218170 TIFF2025525350000179.tif211170 TIFF2025525350000180.tif198170 TIFF2025525350000181.tif186170 TIFF2025525350000182.tif216170 TIFF2025525350000183.tif168170 TIFF2025525350000184.tif213170 TIFF2025525350000185.tif215170 TIFF2025525350000186.tif208170 TIFF2025525350000187.tif215170 TIFF2025525350000188.tif211170 TIFF2025525350000189.tif204170 TIFF2025525350000190.tif208170 TIFF2025525350000191.tif220170 TIFF2025525350000192.tif218170 TIFF2025525350000193.tif233170 TIFF2025525350000194.tif213170 TIFF2025525350000195.tif208170 TIFF2025525350000196.tif213170 TIFF2025525350000197.tif239170 TIFF2025525350000198.tif177170 TIFF2025525350000199.tif236170TIFF2025525350000200.tif169170 TIFF2025525350000201.tif173170 TIFF2025525350000202.tif224170 TIFF2025525350000203.tif233170 TIFF2025525350000204.tif183170 TIFF2025525350000205.tif227170 TIFF2025525350000206.tif168170 TIFF2025525350000207.tif171170 TIFF2025525350000208.tif238170 TIFF2025525350000209.tif168170 TIFF2025525350000210.tif169170 TIFF2025525350000211.tif167170

[0315] Example 8 [4-[(2-chloro-4-fluoro-phenyl)methoxy]-1-piperidyl]-[3-(4-methyl-1H-pyrazol-5-yl)azetidin-1-yl]methanone [ka] To a solution of 5-(azetidin-3-yl)-4-methyl-1H-pyrazole 2,2,2-trifluoroacetic acid (20 mg, 80 μmol, CAS RN 1361115-19-6) in DCM (1 mL) was added DIPEA (42 μL, 239 μmol), followed by 4-nitrophenyl carbonochloridate (15.2 mg, 75.6 μmol, CAS RN 7693-46-1) in one portion. The mixture was stirred at room temperature for 2 hours. The reaction mixture was evaporated to dryness. The residue was dissolved in dioxane (1 mL). 4-[(2-chloro-4-fluorophenyl)methoxy]piperidine (28 mg, 80 μmol, CAS RN 1098356-25-2) was added in one portion, and the mixture was stirred at room temperature for 2 hours. 2M NaOH aqueous solution (796 μl, 1.59 mmol) was added and the RM was heated to 80° C. overnight. After cooling, the mixture was extracted three times with EtOAc. The organic layer was dried over MgSO4, filtered and evaporated. The product was purified using HPLC method YMC to give the desired compound as a yellow amorphous solid (0.002 g; 6.72%). MS (ESI): m / z=407.2 [M+H]+ .

[0316] Example 13 [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(2-methylpyrazol-3-yl)pyrrolidin-1-yl]methanone [ka] To an ice-cold solution of (3-(1H-pyrazol-5-yl)pyrrolidin-1-yl)(3-((2-fluoro-4-(trifluoromethyl)benzyl)oxy)azetidin-1-yl)methanone (73 mg, 177 μmol, Example 1) in THF (1 mL) was added potassium tert-butoxide (23.8 mg, 212 μmol). To the RM was added iodomethane (12.2 μl, 195 μmol) dropwise and stirred at 0° C. for 5 min. The RM was warmed to room temperature and continued stirring for 30 min. The RM was quenched with water and poured into EtOAc. The aqueous layer was extracted three times with EtOAc, and the combined organic layers were dried over MgSO4. The solvent was removed in vacuo. The crude product was purified by HPLC method GN. Two samples of the same mass were collected. This was presumed to be due to methylation to the desired product and tautomer. 2D NMR confirmed that the first eluting compound was the desired product, obtained as a colorless oil (10 mg; 12.6%). MS (ESI): m / z = 427.3 [M+H] + .

[0317] Example 17 [3-[4-(2,4-dichlorophenyl)phenyl]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone [ka] A suspension of (2,4-dichlorophenyl)boronic acid (104 mg, 547 μmol, CAS RN 68716-47-2), (3-(1H-pyrazol-5-yl)pyrrolidin-1-yl)(3-(4-bromophenyl)azetidin-1-yl)methanone (205.2 mg, 547 μmol, BB3), potassium carbonate (378 mg, 2.73 mmol), water (257 μL), and tetrakis(triphenylphosphine)palladium(0) (31.6 mg, 27.3 μmol) in THF (2.57 mL) was stirred at 80° C. for 3 h. The reaction mixture was poured onto water and EtOAc, and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layer was dried over MgSO4, filtered, treated with silica gel, and evaporated. The compound was purified by silica gel chromatography on a 25 g column using an MPLC system eluting with a gradient of n-heptane: EtOAc / ethanol (3 / 1) (70:30 to 10:90) to give the desired compound as a colorless solid. The product was purified using HPLC method YMC to give the desired product as a colorless foam (47.3 mg; 19.6%). MS (ESI): m / z = 441.2 [M+H] + .

[0318] Example 42 (+)- or (-)-[2-(2-chloro-4-fluoro-phenoxy)-7-azaspiro[3.5]nonan-7-yl]-[(3R)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone and Example 43 (-)- or (+)-[2-(2-chloro-4-fluoro-phenoxy)-7-azaspiro[3.5]nonan-7-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone [ka] To a solution of 2-(2-chloro-4-fluorophenoxy)-7-azaspiro[3.5]nonane (38 mg, 143 μmol, CAS RN 2135785-78-1) in ACN (1.5 mL) was added TEA (160 μL, 1.5 mmol), followed by di(1H-1,2,4-triazol-1-yl)methanone (23.5 mg, 143 μmol) in one portion. The mixture was stirred at room temperature for 30 minutes. 5-(pyrrolidin-3-yl)-1H-1,2,4-triazole dihydrochloride (30.3 mg, 143 μmol, CAS RN 1909337-56-9) was added in one portion, and the clear solution was stirred at 65° C. overnight. The reaction mixture was poured onto water and EtOAc, and the layers were separated. The aqueous layer was extracted with EtOAc. The organic layer was washed with 5% aqueous NaHCO3, 0.5M aqueous HCl, and brine, dried over MgSO4, filtered, and evaporated. The racemate was separated by SFC method IC1 to give the desired compound 42 (first elution) as a pale yellow lyoph solid (0.022 g; 31.8%). MS (ESI): m / z = 434.3 [M+H] + and compound 43 (second elution) was obtained as a pale yellow lyoph solid (0.025 g; 36.2%). MS (ESI): m / z = 434.3 [M+H] + .

[0319] Unless otherwise indicated, the following examples were synthesized similarly to the syntheses described for Examples 42 and 43 using the appropriate building blocks, respectively. [Table 6] TIFF2025525350000217.tif172170 TIFF2025525350000218.tif196170 TIFF2025525350000219.tif185170 TIFF2025525350000220.tif186170 TIFF2025525350000221.tif177170 TIFF2025525350000222.tif235170 TIFF2025525350000223.tif172170 TIFF2025525350000224.tif177170 TIFF2025525350000225.tif241170 TIFF2025525350000226.tif205170 TIFF2025525350000227.tif186170 TIFF2025525350000228.tif187170

[0320] Example 83 trans-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]cyclobutyl]-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone [ka] To a solution of trans-3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]cyclobutanecarboxylic acid (50 mg, 132 μmol, BB13) and 5-(pyrrolidin-3-yl)-1H-1,2,3-triazole (18.2 mg, 132 μmol, CAS RN 1517602-91-3) in DMF (0.34 mL), HATU (55 mg, 145 μmol) and DIPEA (92 μL, 0.53 mmol) were added, and the mixture was stirred at room temperature overnight. The product was purified by HPLC method GN to give the desired compound as a pale yellow oil (0.036 g; 50.5%). MS (ESI): m / z = 412.2 [M + H] + .

[0321] Example 821 [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[4-[[5-(trifluoromethyl)pyrazin-2-yl]amino]cuban-1-yl]methanone [ka] The product was obtained in a similar manner to Example 1, starting from 5-[(3S)-pyrrolidin-3-yl]-1H-1,2,4-triazole (CAS RN 2165724-79-6) and 4-[[5-(trifluoromethyl)pyrazin-2-yl]amino]cubane-1-carboxylic acid (BB84), to give the title compound as a colorless solid. MS (ESI): m / z=430.1 [M+H]+.

[0322] Unless otherwise indicated, the following examples were synthesized similarly to the synthesis described for Example 83, using each appropriate building block. [Table 7] TIFF2025525350000232.tif217170

[0323] Example 92 [3-[4-(2-methylazetidin-1-yl)phenyl]azetidin-1-yl]-[(3S or 3R)-3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone [ka] A solution of 5-[(3S or 3R)-pyrrolidin-3-yl]-1H-pyrazole (38.0 mg, 0.280 mmol, BB25), (4-nitrophenyl) 3-[4-(2-methylazetidin-1-yl)phenyl]azetidine-1-carboxylate (50.0 mg, 0.140 mmol, BB20), and DIPEA (0.06 mL, 0.340 mmol) in ACN (3 mL) was stirred for 16 h at 25° C. The solution was concentrated in vacuo to give a residue that was purified by preparative HPLC (Gemini NX column) using a gradient of acetonitrile:water (containing 0.1% formic acid) (18:82 to 100:0). The product was purified by preparative HPLC (Xtimate C18 column) using a gradient of acetonitrile:water (containing 0.05% NH3·H2O) (27:73 to 57:43) to give the desired product as a colorless oil (9 mg, 18.1%). MS (ESI): m / z = 366.2 [M+H] + .

[0324] Unless otherwise indicated, the following examples were synthesized similarly to the synthesis described for Example 92, using each appropriate building block. [Table 8] TIFF2025525350000235.tif209170 TIFF2025525350000236.tif225170 TIFF2025525350000237.tif191170 TIFF2025525350000238.tif219170 TIFF2025525350000239.tif83170

[0325] Example 123 (+)-[4-[(2-chloro-4-fluoro-phenoxy)methyl]-1-piperidyl]-[(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone and Example 124 (-)-[4-[(2-chloro-4-fluoro-phenoxy)methyl]-1-piperidyl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone [ka] A mixture of (4-nitrophenyl) 3-(1H-triazol-5-yl)pyrrolidine-1-carboxylate (305.19 mg, 1.01 mmol, BB27), DIPEA (649.85 mg, 5.03 mmol), and 4-[(2-chloro-4-fluoro-phenoxy)methyl]piperidine (204.0 mg, 0.840 mmol, CAS RN 883527-36-4) in ACN (6 mL) was stirred at 80° C. for 12 hours. The reaction mixture was evaporated under reduced pressure to give a residue, which was then purified by preparative HPLC (Gemini Luna C18 column) and preparative TLC (DCM / MeOH=10 / 1) using a gradient of A:water (containing 0.225% FA) (20:80 to 98:2) to give the racemate. The racemate was then separated by SFC method AD5 to give the desired product Example 123 (first elution) as a white solid (22.6 mg, 6.6% yield) MS (ESI): m / z = 408.0 [M+H] + and the product Example 124 (second elution) was obtained as a white solid (19.6 mg, 5.7% yield). MS (ESI): m / z = 408.0 [M+H] + . Example 123. Specific rotation: +21.10° Example 124. Specific rotation: -17.03°

[0326] Example 134 (-)-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3S or 3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone and Example 135 (+)-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3S or 3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone Example 136 (-)-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3S or 3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone and Example 137 (+)-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3S or 3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone [ka] To a solution of 3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidine 2,2,2-trifluoroacetic acid (200.0 mg, 0.530 mmol, CAS RN2411576-99-1) and DIPEA (1.0 mL, 2.12 mmol) in ACN (15 mL), (4-nitrophenyl)(3S or 3R)-3-(1H-triazol-5-yl)pyrrolidine-1-carboxylate (176.86 mg, 0.580 mmol, BB28) was added, and the mixture was stirred at 80 °C for 12 h. The reaction mixture was poured into HO (5 mL), extracted with EtOAc (5 mL × 3), and the organic layer was evaporated. The crude product was purified by preparative HPLC (0.225% v / v FA) and lyophilized to give the racemate. The racemate was separated using SFC method AD7 to give the desired product 136 as a white solid (18 mg, 7.7%) MS(ESI): m / z=428.1 [M+H] + and the desired product 137 as a white solid (13 mg, 5.7%) MS (ESI): m / z = 428.1 [M+H] + as well as an impure mixture of products 134 and 135.

[0327] This impure mixture was separated using SFC method ADH3 to give the desired product 134 as a white solid (10.2 mg, 4.5%) MS(ESI): m / z=428.1 [M+H] + and the desired product 135 as a white solid (10.6 mg, 4.7%) MS (ESI): m / z = 428.1 [M+H] + was obtained as. Example 134. Specific rotation: -56.53° Example 135. Specific rotation: +20.36° Example 136. Specific rotation: -38.24° Example 137. Specific rotation: +20.12°

[0328] Example 138 (+)-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3R or 3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone and Example 139 (-)-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3R or 3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone Example 140 (-)-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3R or 3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone and Example 141 (+)-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3R or 3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone [ka] To a solution of 3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidine 2,2,2-trifluoroacetic acid (200.0 mg, 0.530 mmol, CAS RN2411576-99-1) and DIPEA (1.0 mL, 2.12 mmol) in ACN (15 mL), (4-nitrophenyl)(3R or 3S)-3-(1H-triazol-5-yl)pyrrolidine-1-carboxylate (176.86 mg, 0.580 mmol, BB29) was added, and the mixture was stirred at 80 °C for 12 h. The reaction mixture was poured into HO (5 mL), extracted with EtOAc (5 mL × 3), and the organic layer was evaporated. The crude product was purified by preparative HPLC (0.225% v / v FA) and lyophilized to give the racemate. The racemate was separated using SFC Method IG to give the desired product 140 as a white solid (26.2 mg, 8%) MS(ESI): m / z=428.1 [M+H] + and the desired product 141 as a white solid (17.2 mg, 4.9%) MS (ESI): m / z = 428.1 [M+H] + as well as an impure mixture of products 140 and 141.

[0329] This impure mixture was separated using SFC Method IG to give the desired product 138 as a white solid (6.5 mg, 2%) MS(ESI): m / z=428.1 [M+H] + and the desired product 139 as a white solid (5.6 mg, 1.7%) MS (ESI): m / z = 428.1 [M+H] + was obtained as. Example 138. Specific rotation: +48.08° Example 139. Specific rotation: -45.84° Example 140. Specific rotation: -13.67° Example 141. Specific rotation: +55.40°

[0330] Example 182 Sodium [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[rac-(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone [ka]

[0331] To a solution of (S)-(3-(1H-1,2,3-triazol-5-yl)pyrrolidin-1-yl)(3-((2-fluoro-4-(trifluoromethyl)benzyl)oxy)azetidin-1-yl)methanone (50 mg, 121 μmol, Example 36) in MeOH (0.2 mL) and THF (0.1 mL) was added sodium methoxide 30% in MeOH (22.5 μL, 121 μmol), and the clear, colorless solution was stirred at room temperature for 2.5 hours. TBME (2 mL) was added dropwise, which resulted in precipitation. The suspension was stirred at room temperature for 4 hours and then filtered. The filter cake was washed with TBME and dried under high vacuum to give the desired compound as a colorless solid (0.035 g; 66.5%). MS (ESI): m / z=414.2 [M+H] + .

[0332] The following examples were prepared similarly to Examples 1-841 using building blocks that are either commercially available or synthesized by one skilled in the art, as well as the building blocks described in this application from BB1 to BB119. [Table 9] TIFF2025525350000245.tif243170 TIFF2025525350000246.tif226170 TIFF2025525350000247.tif234170 TIFF2025525350000248.tif243170 TIFF2025525350000249.tif237170 TIFF2025525350000250.tif239170 TIFF2025525350000251.tif223170 TIFF2025525350000252.tif229170 TIFF2025525350000253.tif219170 TIFF2025525350000254.tif247170 TIFF2025525350000255.tif240170 TIFF2025525350000256.tif228170 TIFF2025525350000257.tif250170 TIFF2025525350000258.tif239170 TIFF2025525350000259.tif239170 TIFF2025525350000260.tif247170 TIFF2025525350000261.tif245170 TIFF2025525350000262.tif245170 TIFF2025525350000263.tif232170 TIFF2025525350000264.tif235170 TIFF2025525350000265.tif243170 TIFF2025525350000266.tif228170 TIFF2025525350000267.tif245170 TIFF2025525350000268.tif246170 TIFF2025525350000269.tif235170 TIFF2025525350000270.tif236170 TIFF2025525350000271.tif243170 TIFF2025525350000272.tif230170 TIFF2025525350000273.tif245170 TIFF2025525350000274.tif236170 TIFF2025525350000275.tif226170 TIFF2025525350000276.tif237170 TIFF2025525350000277.tif250170 TIFF2025525350000278.tif221170 TIFF2025525350000279.tif245170 TIFF2025525350000280.tif246170 TIFF2025525350000281.tif221170 TIFF2025525350000282.tif230170 TIFF2025525350000283.tif249170 TIFF2025525350000284.tif236170 TIFF2025525350000285.tif230170 TIFF2025525350000286.tif243170 TIFF2025525350000287.tif239170 TIFF2025525350000288.tif243170 TIFF2025525350000289.tif250170 TIFF2025525350000290.tif229170 TIFF2025525350000291.tif231170 TIFF2025525350000292.tif229170 TIFF2025525350000293.tif250170 TIFF2025525350000294.tif251170 TIFF2025525350000295.tif221170 TIFF2025525350000296.tif245170 TIFF2025525350000297.tif239170 TIFF2025525350000298.tif243170 TIFF2025525350000299.tif244170 TIFF2025525350000300.tif229170 TIFF2025525350000301.tif224170 TIFF2025525350000302.tif235170 TIFF2025525350000303.tif246170 TIFF2025525350000304.tif250170 TIFF2025525350000305.tif251170 TIFF2025525350000306.tif230170 TIFF2025525350000307.tif224170 TIFF2025525350000308.tif222170 TIFF2025525350000309.tif234170 TIFF2025525350000310.tif235170 TIFF2025525350000311.tif234170 TIFF2025525350000312.tif249170 TIFF2025525350000313.tif215170 TIFF2025525350000314.tif227170 TIFF2025525350000315.tif227170 TIFF2025525350000316.tif239170 TIFF2025525350000317.tif245170 TIFF2025525350000318.tif248170 TIFF2025525350000319.tif239170 TIFF2025525350000320.tif50170

[0333] Building Block Synthesis BB1 6-(2-chloro-4-fluoro-phenoxy)-2-azaspiro[3.3]heptane; 2,2,2-trifluoroacetic acid Step 1: tert-Butyl 6-(2-chloro-4-fluoro-phenoxy)-2-azaspiro[3.3]heptane-2-carboxylate To a solution of 2-chloro-4-fluorophenol (756 mg, 562 μL, 5.16 mmol, CAS RN 1996-41-4), tert-butyl 6-hydroxy-2-azaspiro[3.3]heptane-2-carboxylate (1 g, 4.69 mmol, CAS RN 1147557-97-8), and triphenylphosphine (1.48 g, 5.63 mmol) in THF (23.4 mL) was added dropwise DIAD (1.09 mL, 5.63 mmol, CAS N 2446-83-5) at 0° C., and the reaction was stirred at room temperature for 18 hours. Another batch of triphenylphosphine (738 mg, 2.81 mmol) was added, followed by DIAD (547 μL, 2.81 mmol), and the reaction was stirred at room temperature for 6 hours. The reaction mixture was poured into saturated aqueous NaHCO3 (50 mL) and EtOAc (30 mL) was added. The phases were separated and the aqueous phase was extracted with EtOAc. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated to give an orange oil. The crude product was immobilized on Isolute and purified by column chromatography (40 gr, 0→30% EtOAc in Hepto) to give the desired product as a yellow solid (1.50 g, 89.3% yield). MS (ESI): m / z = 286.2 [M-C4H8+H] + .

[0334] Step 2: 6-(2-chloro-4-fluoro-phenoxy)-2-azaspiro[3.3]heptane; 2,2,2-trifluoroacetic acid To a solution of tert-butyl 6-(2-chloro-4-fluorophenoxy)-2-azaspiro[3.3]heptane-2-carboxylate (1.5065 g, 4.41 mmol) in DCM (22 mL) was added 2,2,2-trifluoroacetic acid (2.72 mL, 35.3 mmol), and the reaction was stirred at room temperature for 3.5 hours. The reaction mixture was concentrated to give the desired product as a yellow oil (2.015 g, 100% yield). MS (ESI): m / z = 242.2 [M+H] + .

[0335] BB2 3-((2-Fluoro-4-(pentafluoro-16-sulfanyl)benzyl)oxy)azetidine 2,2,2-trifluoroacetic acid Step 1: tert-butyl 3-((2-fluoro-4-(pentafluoro-16-sulfanyl)benzyl)oxy)azetidine-1-carboxylate To a solution of tert-butyl 3-hydroxyazetidine-1-carboxylate (5.5 g, 31.8 mmol, CAS RN 141699-55-0) in dry THF (4 mL) was added a 1 M solution of potassium tert-butoxide in THF (33.3 mL, 33.3 mmol). The cloudy reaction mixture was stirred at room temperature for 15 minutes, followed by the addition of (4-(bromomethyl)-3-fluorophenyl)pentafluoro-16-sulfane (10 g, 31.8 mmol, CAS RN 1240257-17-3). The reaction mixture was then stirred at room temperature for 19 hours. The crude reaction mixture was diluted with EtOAc, extracted with water, the organic phase was collected, and the aqueous phase was back-extracted with EtOAc. The combined organic phases were dried over sodium sulfate and evaporated to dryness. The crude material was purified by flash chromatography (silica gel, 330 g, 0% to 80% EtOAc in heptane): 9.72 g, yellow oil. MS (ESI): m / z = 352.1 [M-C4H8+H] + .

[0336] Step 2: 3-((2-fluoro-4-(pentafluoro-16-sulfanyl)benzyl)oxy)azetidine 2,2,2-trifluoroacetic acid To a solution of tert-butyl 3-((2-fluoro-4-(pentafluoro-16-sulfanyl)benzyl)oxy)azetidine-1-carboxylate (9.72 g, 23.9 mmol) in DCM (100 ml) was added TFA (27.2 g, 18.4 ml, 239 mmol). The resulting reaction mixture was stirred at room temperature for 1 hour and then evaporated. The residue was treated with toluene and evaporated to give the desired product as a yellow oil (10.1 g, 100%). 308.1 [M+H] + .

[0337] BB3 (3-(1H-pyrazol-5-yl)pyrrolidin-1-yl)(3-(4-bromophenyl)azetidin-1-yl)methanone The product was obtained in a similar manner to Example 1, starting from 3-(4-bromophenyl)azetidine (CAS RN 7215-01-2) and 5-(pyrrolidin-3-yl)-1H-pyrazole dihydrochloride (CAS RN 2173135-18-5), to give the title compound as a colorless gum. MS (ESI): m / z = 375.2 [M+H]+.

[0338] BB4 6-Pyrrolidin-3-yl-1H-pyrazin-2-one hydrobromide To a solution of tert-butyl 3-(6-methoxypyrazin-2-yl)pyrrolidine-1-carboxylate (82 mg, 294 μmol, CAS RN 2355015-85-7) in EtOH (0.3 mL) was added 48% aqueous HBr (365 μl, 3.23 mmol) and the RM was heated at 90° C. for 15 h. The RM was concentrated in vacuo to give the desired compound as a brown solid. MS (ESI): m / z=166.1 [M+H] + .

[0339] BB5 (+) or (-)-[1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidin-3-yl]oxazolidin-2-one and BB6 (-) or (+)-[1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidin-3-yl]oxazolidin-2-one The diastereomeric racemates of 4-[1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidin-3-yl]oxazolidin-2-one (Example 3) were separated using HPLC method GN to give the desired product BB5 (first elution) as a colorless solid (21.3 mg, 4.33%). MS (ESI): m / z = 432.2 [M + H] + and the desired product BB6 (second elution) was obtained as a colorless solid (59.5 mg, 12.1%). MS (ESI): m / z = 432.2 [M+H] + .

[0340] BB7 5-Pyrrolidin-3-ylpyrrolidin-2-one 4-Methylbenzenesulfonic acid [ENTITY A] Step 1: tert-butyl 3-[1-(benzyloxycarbonylamino)-2-methoxy-2-oxo-ethyl]pyrrolidine-1-carboxylate To a mixture of tert-butyl 3-(1-amino-2-methoxy-2-oxoethyl)pyrrolidine-1-carboxylate (1.5 g, 5.81 mmol, CAS RN 1135916-70-9) in DCM (15 mL) and saturated NaHCO solution in HO (10 mL, 5.81 mmol) was added benzyl carbonochloridate (829 μL, 5.81 mmol) dropwise over 80 min at room temperature under vigorous stirring. The biphasic mixture was stirred at room temperature for 20 min. The layers were separated. The aqueous layer was extracted twice with DCM. The organic layer was extracted once with water and once with brine, dried over MgSO, filtered, treated with silica gel, and evaporated. The compound was purified by silica gel chromatography on a 40 g column using an MPLC (ISCO) system eluting with a gradient of n-heptane: EtOAc (100:0 to 30:70) to give the desired compound as a colorless oil (2.06 g; 88.6%). MS (ESI): m / z = 293.2 [M-BOC+H]+ .

[0341] Step 2: tert-butyl 3-[1-(benzyloxycarbonylamino)-2-hydroxy-ethyl]pyrrolidine-1-carboxylate [ENTITY A] and tert-butyl 3-[1-(benzyloxycarbonylamino)-2-hydroxy-ethyl]pyrrolidine-1-carboxylate [ENTITY B] To an ice-cold solution of tert-butyl 3-[1-(benzyloxycarbonylamino)-2-methoxy-2-oxo-ethyl]pyrrolidine-1-carboxylate (1.71 g, 4.36 mmol) in THF (19.5 mL) was added dropwise a 2 M solution of LiBH in THF (4.36 mL, 8.71 mmol). The clear solution was stirred at room temperature for 2 h. The reaction mixture was poured into saturated aqueous potassium sodium tartrate and EtOAc, and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layer was washed with water, dried over MgSO, filtered, loaded onto silica gel, and evaporated. The compound was purified three times by silica gel chromatography on an 80 g column using an MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100) to give the desired product [ENTITY A] (first elution) and [ENTITY B] (second elution). MS(ESI): m / z=265.2[M-C4H8+H]+.

[0342] Step 3: tert-butyl 3-[1-(benzyloxycarbonylamino)-2-oxo-ethyl]pyrrolidine-1-carboxylate [ENTITY A] To an ice-cold solution of tert-butyl 3-[1-(benzyloxycarbonylamino)-2-hydroxyethyl]pyrrolidine-1-carboxylate (660 mg, 1.81 mmol, [ENTITY A]) in DCM (15 mL) was added DMP (1.08 g, 2.54 mmol, CAS RN 87413-09-0), and the mixture was stirred at 0 °C for 1.75 h. The reaction mixture was diluted with DCM and 2 M aqueous Na2CO3, and the layers were separated. The aqueous layer was extracted twice with DCM. The organic layer was washed with 10% aqueous sodium thiosulfate and brine, dried over MgSO4, filtered, loaded onto silica gel, and evaporated. The compound was purified by silica gel chromatography on a 12 g column using an MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100) to give the desired compound as a colorless gum (0.530 g; 80.7%). MS (ESI): m / z = 263.1 [M-BOC + H] + .

[0343] Step 4: tert-butyl 3-[(E)-1-(benzyloxycarbonylamino)-4-ethoxy-4-oxo-but-2-enyl]pyrrolidine-1-carboxylate [ENTITY A] To an ice-cold solution of ethyl 2-(diethoxyphosphoryl)acetate (290 μL, 1.46 mmol) in THF (5 mL) was added sodium hydride 55% in mineral oil (63.8 mg, 1.46 mmol), and the mixture was stirred at this temperature for 30 minutes. A solution of tert-butyl 3-[1-(benzyloxycarbonylamino)-2-oxo-ethyl]pyrrolidine-1-carboxylate (530 mg, 1.46 mmol) in THF (11 mL) was added dropwise. Stirring was continued for 1.5 hours at ice bath temperature. The reaction mixture was poured onto water and EtOAc, and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layer was dried over MgSO4, filtered, treated with silica gel, and evaporated. The compound was purified by silica gel chromatography on a 12 g column using an MPLC system eluting with a gradient of n-heptane: EtOAc (100:0 to 50:50) to give the desired compound as a colorless gum (0.519 g; 73.8%). MS (ESI): m / z = 377.2 [M-C4H8+H] + .

[0344] Step 5: tert-butyl 3-(5-oxopyrrolidin-2-yl)pyrrolidine-1-carboxylate [ENTITY A] Under argon, a mixture of tert-butyl 3-[(E)-1-(benzyloxycarbonylamino)-4-ethoxy-4-oxo-but-2-enyl]pyrrolidine-1-carboxylate (205 mg, 474 μmol) and ammonium formate (598 mg, 9.48 mmol) in MeOH (4 mL) was treated with Pd—C 10% (5.04 mg, 47.4 μmol) and stirred at reflux in a sealed tube for 4.5 h. The reaction mixture was filtered. The filtrate was evaporated. The residue was dissolved in dilute aqueous NaHCO3 and EtOAc, and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layer was dried over MgSO4, filtered, and evaporated to give the desired compound as a colorless solid (0.112 g; 92.9%). MS (ESI): m / z = 199.1 [M-C4H8+H] + .

[0345] Step 6: 5-Pyrrolidin-3-ylpyrrolidin-2-one 4-methylbenzenesulfonic acid [ENTITY A] A suspension of tert-butyl 3-(5-oxopyrrolidin-2-yl)pyrrolidine-1-carboxylate (75 mg, 295 μmol) and p-toluenesulfonic acid monohydrate (67.3 mg, 354 μmol) in EtOAc (0.8 mL) was heated at reflux for 1 h and subsequently stirred at room temperature overnight. The mixture was homogenized in an ultrasonic bath filled with ice water. The suspension was filtered. The filter cake was washed with EtOAc to give the desired compound as a pale yellow solid (0.085 g; 72.4%). MS (ESI): m / z = 155.1 [M+H] + .

[0346] BB8 5-Pyrrolidin-3-ylpyrrolidin-2-one 4-Methylbenzenesulfonic acid [ENTITY B] Starting from tert-butyl 3-[1-(benzyloxycarbonylamino)-2-hydroxyethyl]pyrrolidine-1-carboxylate [ENTITY B] (BB7, step 2), the product was obtained in a similar manner to BB7, steps 3-6, to give the title compound as a colorless solid. MS (ESI): m / z = 155.1 [M+H] + .

[0347] BB9 3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine 4-methylbenzenesulfonic acid Step 1: tert-butyl 3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-carboxylate In a 20 mL vial equipped with a stir bar, add 1-bromo-4-(1-(trifluoromethyl)cyclopropyl)benzene (561 mg, 2.12 mmol, 1.0 equiv.; CAS RN 1227160-18-0), tert-butyl 3-iodoazetidine-1-carboxylate (600 mg, 2.12 mmol, 1.0 equiv.; CAS RN The solution (254454-54-1), tris(trimethylsilyl)silane (527 mg, 653 μL, 2.12 mmol, 1.0 equiv.), photocatalyst bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl]phenyl]iridium(1+) 4-tert-butyl-2-(4-tert-butyl-2-pyridyl)pyridine hexafluorophosphate (23.8 mg, 21.2 μmol, 0.01 equiv.; Ir[dF(CF3)ppy]2(dtbbpy))PF6, CAS RN 870987-63-6), and anhydrous sodium carbonate (449 mg, 4.24 mmol, 2.0 equiv.) were added. The vial was sealed and placed under Ar, followed by the addition of dimethoxyethane (9 mL). To a separate vial, nickel(II) chloride ethylene glycol dimethyl ether complex (4.65 mg, 21.2 μmol, 0.01 equiv.; CAS RN 29046-78-4) and 4,4'-di-tert-butyl-2,2'-bipyridine (5.68 mg, 21.2 μmol, 0.01 equiv.) were added. The vial was sealed, purged with Ar, and dimethoxyethane (4 mL) was added. The precatalyst solution was sonicated for 5 min, after which 2 mL was injected into the reaction vessel. The reaction mixture was degassed with Ar and irradiated with a blue LED lamp (420 nm) for 1 h. The reaction was quenched by exposure to air, filtered, and the solvent was evaporated. The crude reaction mixture was purified by silica gel chromatography using an MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 70:30) to afford the title compound as a colorless solid (0.51 g, 66%). MS(ESI): m / z=286.1[M-C4H8+2H] + .

[0348] Step 2: 3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine 4-methylbenzenesulfonic acid To a solution of tert-butyl 3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-carboxylate (0.5 g, 1.46 mmol, 1.0 equiv.) in EtOAc (5 mL) was added 4-methylbenzenesulfonic acid hydrate (0.29 g, 1.54 mmol, 1.1 equiv.) and the mixture was heated at reflux for 2 h. The suspension was cooled in a 0° C. refrigerator for 1 h and filtered. The precipitate was washed with EtOAc and dried to give the title compound as a colorless solid (0.52 g, 82%). MS (ESI): m / z=242.2 [M+H] + .

[0349] BB10 6-(2,4-Difluorobenzyl)-2-azaspiro[3.3]heptane 2,2,2-trifluoroacetic acid Step 1: (2,4-Difluorobenzyl)triphenylphosphonium bromide Under argon, triphenylphosphine (2.53 g, 9.66 mmol) was dissolved in acetonitrile (25 ml) and 1-(bromomethyl)-2,4-difluorobenzene (2.00 g, 1.24 ml, 9.66 mmol, CAS RN 23915-07-3) was added. The mixture was stirred at 80 °C for 1 hour. The suspension was cooled to room temperature. To this was added 250 mL of TBME and stirred at room temperature for 30 minutes. The solid was filtered and washed with TBME to give the desired product as a colorless solid (4.5 g; 100%). MS (ESI): m / z = 389.2 [M-Br+H] + .

[0350] Step 2: tert-Butyl 6-(2,4-difluorobenzylidene)-2-azaspiro[3.3]heptane-2-carboxylate Under argon at -78°C, (2,4-difluorobenzyl)triphenylphosphonium bromide (4.6 g, 9.8 mmol) was dissolved in dry THF (46 ml) and LHMDS 1M in THF (19.6 ml, 19.6 mmol) was added. The reaction mixture was stirred at -78°C for 2 hours. Then, at room temperature, tert-butyl 6-oxo-2-azaspiro[3.3]heptane-2-carboxylate (4.14 g, 19.6 mmol, CAS RN 1181816-12-5) was added, and the mixture was stirred at 85°C overnight. After cooling, TBME was added. The suspension was filtered. The filtrate was concentrated and then purified by flash chromatography (silica gel, 100 g, 0% to 80% EtOAc in heptane). The residue was treated with toluene and evaporated to give the desired product as a yellow oil (10.1 g, 100%). 308.1[M+H] + .

[0351] Step 3: tert-butyl 6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptane-2-carboxylate A solution of tert-butyl 6-(2,4-difluorobenzylidene)-2-azaspiro[3.3]heptane-2-carboxylate (1.66 g, 5.17 mmol) was dissolved in EtOAc (30 mL). The flask was purged and backfilled with argon (×3). Pd—C (550 mg, 517 μmol, Eq: 0.1) was added, and the reaction was stirred under a hydrogen balloon for 3 hours. The reaction mixture was filtered through a Celite pad, washed with EtOAc, and dried under vacuum to give the desired crude product (1.44 g, 86.2%). 268.2 [M-C4H8+H] + .

[0352] Step 4: 6-(2,4-difluorobenzyl)-2-azaspiro[3.3]heptane 2,2,2-trifluoroacetic acid To a solution of tert-butyl 6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptane-2-carboxylate (1.44 g, 4.45 mmol) in DCM (28.8 mL) was added TFA (1.72 mL, 22.3 mmol). The resulting reaction mixture was stirred at room temperature for 2 hours. The mixture was evaporated to give the desired crude product as a colorless oil (1.8 g). 224.1 [M+H] + .

[0353] BB11 2-[2-fluoro-4-(trifluoromethyl)phenoxy]-7-azaspiro[3.5]nonane 2,2,2-trifluoroacetic acid Step 1: tert-butyl 2-[2-fluoro-4-(trifluoromethyl)phenoxy]-7-azaspiro[3.5]nonane-7-carboxylate To a solution of tert-butyl 2-hydroxy-7-azaspiro[3.5]nonane-7-carboxylate (442 mg, 1.83 mmol; CAS RN 240401-28-9) in THF (8 mL) was added 2-fluoro-4-(trifluoromethyl)phenol (330 mg, 1.83 mmol; CAS RN 77227-78-2) and triphenylphosphine (529 mg, 2.02 mmol, Eq: 1.1). After stirring at room temperature for 5 minutes, the solution was cooled in an ice bath and DEAD (351 mg, 319 μl, 2.02 mmol, Eq: 1.1) was added dropwise over 10 minutes. After stirring in the ice bath for 1 hour, the mixture was stirred at room temperature for 5 hours. The reaction mixture was poured onto water and diethyl ether, and the layers were separated. The organic layer was washed with water, 1 M aqueous NaOH, and brine, dried over MgSO4, filtered, and evaporated. The compound was purified by silica gel chromatography on a 25 g column using an MPLC system eluting with a gradient of n-heptane: EtOAc (100:0 to 60:40) to give the desired compound as a colorless solid (0.625 g; 83.9%). MS (ESI): m / z = 348.1 [M-C4H8+H] + .

[0354] Step 2: 2-[2-fluoro-4-(trifluoromethyl)phenoxy]-7-azaspiro[3.5]nonane 2,2,2-trifluoroacetic acid To a solution of tert-butyl 2-[2-fluoro-4-(trifluoromethyl)phenoxy]-7-azaspiro[3.5]nonane-7-carboxylate (70 mg, 174 μmol) in DCM (1 mL) was added TFA (66.8 μL, 868 μmol), and the mixture was stirred at room temperature for 20 h. Evaporation of the solution afforded the desired product as a colorless solid (0.073 g, 100%). 304.2 [M+H] + .

[0355] BB12 3-[4-(2,4-difluorophenyl)phenyl]azetidine 4-methylbenzenesulfonic acid Step 1: tert-butyl 3-[4-(2,4-difluorophenyl)phenyl]azetidine-1-carboxylate A suspension of tert-butyl 3-(4-bromophenyl)azetidine-1-carboxylate (1.3 g, 4.16 mmol, CAS RN 1203681-52-0), (2,4-difluorophenyl)boronic acid (658 mg, 4.16 mmol, CAS RN 144025-03-6), potassium carbonate (2.88 g, 20.8 mmol), water (1 ml), and tetrakis(triphenylphosphine)palladium(0) (241 mg, 208 μmol) in THF (10 ml) was heated at 110 °C for 15 min via microwave irradiation. The crude product was then poured into EtOAc and water. The aqueous layer was extracted with EtOAc (×3), and the solvent was removed in vacuo. The crude product was purified by flash chromatography (Hept:EE 100:0 to 50:50). The product fractions were dried in vacuo to give the product as a yellow oil (1.20; 78.7%). MS (ESI): m / z = 290.2 [M-C4H8+H] + .

[0356] Step 2: 3-[4-(2,4-difluorophenyl)phenyl]azetidine 4-methylbenzenesulfonic acid The product was obtained in a similar manner to BB9, step 2, starting from tert-butyl 3-[4-(2,4-difluorophenyl)phenyl]azetidine-1-carboxylate to give the title compound as a colorless solid. MS (ESI): m / z=246.2 [M+H] + .

[0357] BB13 trans-3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]cyclobutanecarboxylic acid Step 1: trans-methyl 3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]cyclobutanecarboxylate To an ice-cold solution of methyl 3-hydroxycyclobutanecarboxylate (506 mg, 3.89 mmol, CAS RN 63485-51-8) in DMF (8.33 mL) was added sodium hydride 55% in mineral oil (187 mg, 4.28 mmol), and the mixture was stirred at this temperature for 30 min. A solution of 1-(bromomethyl)-2-fluoro-4-(trifluoromethyl)benzene (1 g, 3.89 mmol, CAS RN 239087-07-1) in DMF (1.67 mL) was added dropwise to the mixture at 0 °C. Stirring of the slurry was continued at room temperature for 3 h. The reaction mixture was poured into saturated aqueous NH4Cl (300 mL) and EtOAc (300 mL), and the layers were separated. The aqueous layer was extracted once with EtOAc (100 mL). The organic layer was washed twice with water, dried over MgSO4, filtered, and evaporated to give the desired product as a colorless solid. MS (ESI): m / z = 307.1 [M+H] + It was used as is in the next step.

[0358] Step 2: trans-3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]cyclobutanecarboxylic acid To a solution of methyl 3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]cyclobutanecarboxylate (730 mg, 2.38 mmol) in THF (10 mL), MeOH (10 mL), and water (10 mL) was added LiOH monohydrate (500 mg, 11.9 mmol), and the mixture was stirred at room temperature overnight. The reaction mixture was then poured into water, and the pH was set to 2 using 1 M aqueous HCl. The aqueous layer was extracted twice with EtOAc. The organic layer was dried over Na2SO4, filtered, and evaporated to give the desired product as a pale yellow liquid (646 mg, 63.1%). MS (ESI): m / z = 291.2 [MH] - .

[0359] BB14 [3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]-[3-(4-tetrahydropyran-4-ylphenyl)azetidin-1-yl]methanone Step 1: tert-butyl 3-(4-tetrahydropyran-4-ylphenyl)azetidine-1-carboxylate The product was obtained in the same manner as BB9, step 1, starting from tert-butyl 3-(4-bromophenyl)azetidine-1-carboxylate (CAS RN 1203681-52-0) and 4-bromo-tetrahydropyran (CAS N 25637-16-5) to give the title compound as a pale yellow solid. MS (ESI): m / z = 262.0 [M-C4H8+H] + .

[0360] Step 2: 3-(4-tetrahydropyran-4-ylphenyl)azetidine hydrochloride A solution of tert-butyl 3-(4-tetrahydropyran-4-ylphenyl)azetidine-1-carboxylate (500.0 mg, 1.58 mmol) in 4 M HCl in EtOAc (10.0 mL, 40 mmol) was stirred at room temperature for 4 hours. The solution was concentrated in vacuo to give the desired product as a yellow oil (399 mg, 74.8%). MS (ESI): m / z = 218.5 [M+H] + .

[0361] Step 3: (4-Nitrophenyl) 3-(4-tetrahydropyran-4-ylphenyl)azetidine-1-carboxylate A solution of 3-(4-tetrahydropyran-4-ylphenyl)azetidine hydrochloride (150.0 mg, 0.590 mmol), 4-nitrophenyl chloroformate (120.0 mg, 0.600 mmol, CAS RN 7693-46-1), and TEA (0.2 mL, 1.43 mmol) in DCM (4 mL) was stirred at room temperature for 3 hours. The solution was concentrated in vacuo to give a residue, which was purified by flash column (peroxyl ether: EtOAc = 3:1) to give the desired product as a colorless oil (170 mg, 74.4%). MS (ESI): m / z = 383.3 [M+H] + .

[0362] Step 4: [3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]-[3-(4-tetrahydropyran-4-ylphenyl)azetidin-1-yl]methanone The product was obtained in the same manner as in Example 8, starting from (4-nitrophenyl) 3-(4-tetrahydropyran-4-ylphenyl)azetidine-1-carboxylate and 5-(pyrrolidin-3-yl)-1H-pyrazole hydrochloride (CAS RN 1956389-94-8), to give the title compound as a colorless oil. MS (ESI): m / z = 381.1 [M + H] + . Unless otherwise indicated, the following building blocks were synthesized similarly to the synthesis described for BB14, using the appropriate building blocks for each. [Table 10]

[0363] BB19 [3-[4-[(1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl]phenyl]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone Step 1: tert-butyl 3-[4-[(1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl]phenyl]azetidine-1-carboxylate To a solution of X-PHOS (152.7 mg, 0.320 mmol, CAS RN 564483-18-7) and sodium tert-butoxide (307.82 mg, 3.2 mmol) in DME (20 mL) was added Pd(dba) (293.31 mg, 0.320 mmol), tert-butyl 3-(4-bromophenyl)azetidine-1-carboxylate (500.0 mg, 1.6 mmol, CAS RN 1203681-52-0), and 8-oxa-3-azabicyclo[3.2.1]octane hydrochloride (239.62 mg, 1.6 mmol, CAS RN 54745-74-3), and the mixture was stirred at 110 °C for 12 h under a N atmosphere. The mixture was diluted with water (20 mL) and extracted with DCM (20 mL × 3). The combined organic layers were concentrated under reduced pressure. The residue was purified by silica gel chromatography (petroleum ether: EtOAc = 3:1) to give the desired product as a pale yellow oil (280 mg, 49.2%). MS (ESI): m / z = 345.1 [M + H] + .

[0364] Step 2: rac-(1R,5S)-3-[4-(azetidin-3-yl)phenyl]-8-oxa-3-azabicyclo[3.2.1]octane 2,2,2-trifluoroacetic acid The product was obtained in a similar manner to BB14, step 2, starting from tert-butyl 3-[4-[(1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl]phenyl]azetidine-1-carboxylate and TFA to give the title compound as a pale yellow oil. MS (ESI): m / z = 245.1 [M+H] + .

[0365] Step 3: (4-nitrophenyl) 3-[4-[(1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl]phenyl]azetidine-1-carboxylate The product was obtained in a similar manner to BB14, step 3, starting from rac-(1R,5S)-3-[4-(azetidin-3-yl)phenyl]-8-oxa-3-azabicyclo[3.2.1]octane 2,2,2-trifluoroacetic acid to give the title compound as a yellow oil, which was used directly in the next step.

[0366] Step 4: [3-[4-[(1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl]phenyl]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone The product was obtained in the same manner as in Example 8, starting from (4-nitrophenyl) 3-[4-[(1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl]phenyl]azetidine-1-carboxylate and 5-(pyrrolidin-3-yl)-1H-pyrazole hydrochloride (CAS RN 1956389-94-8), to give the title compound as a colorless oil. MS (ESI): m / z = 408.3 [M + H] + .

[0367] BB20 (4-Nitrophenyl)3-[4-(2-methylazetidin-1-yl)phenyl]azetidine-1-carboxylate The product was obtained in a similar manner to BB19, steps 1-3, starting from tert-butyl 3-(4-bromophenyl)azetidine-1-carboxylate (CAS RN 1203681-52-0) and 2-methylazetidine hydrochloride to give the title compound as a brown solid. MS (ESI): m / z = 368.3 [M-C4H8+H] + .

[0368] BB21 (4-Nitrophenyl)3-[4-(3-fluoropyrrolidin-1-yl)phenyl]azetidine-1-carboxylate Step 1: tert-butyl 3-[4-(3-hydroxypyrrolidin-1-yl)phenyl]azetidine-1-carboxylate The product was obtained in a similar manner to BB19, step 1, starting from tert-butyl 3-(4-bromophenyl)azetidine-1-carboxylate (CAS RN 1203681-52-0) and pyrrolidin-3-ol to give the title compound as a pale yellow solid. MS (ESI): m / z = 319.4 [M+H] + .

[0369] Step 2: tert-butyl 3-[4-(3-fluoropyrrolidin-1-yl)phenyl]azetidine-1-carboxylate To a solution of tert-butyl 3-[4-(3-hydroxypyrrolidin-1-yl)phenyl]azetidine-1-carboxylate (130.0 mg, 0.410 mmol) in DCM (5 mL) was added diethylaminosulfur trifluoride (100.0 mg, 0.620 mmol). The reaction solution was stirred at 25 °C for 16 hours. The solution was poured into brine (10 mL) and extracted with DCM (10 mL). The organic layer was concentrated in vacuo to give a residue, which was purified by flash column (petroleum ether: EtOAc = 10:1) to give the title compound as a colorless solid (105 mg, 80.2%). MS (ESI): m / z = 321.1 [M + H] + .

[0370] Step 3: 1-[4-(azetidin-3-yl)phenyl]-3-fluoro-pyrrolidine 2,2,2-trifluoroacetic acid The product was obtained in a similar manner to BB14, step 2, starting from tert-butyl 3-[4-(3-fluoropyrrolidin-1-yl)phenyl]azetidine-1-carboxylate and TFA to give the title compound as a colorless oil. MS (ESI): m / z = 221.1 [M+H] + .

[0371] Step 4: (4-nitrophenyl) 3-[4-(3-fluoropyrrolidin-1-yl)phenyl]azetidine-1-carboxylate The product was obtained in a similar manner to BB14, step 3, starting from 1-[4-(azetidin-3-yl)phenyl]-3-fluoro-pyrrolidine 2,2,2-trifluoroacetic acid to give the title compound as a brown solid. MS (ESI): m / z = 386.1 [M-C4H8+H] + .

[0372] BB24 3-(4-((1,1,1-trifluoro-2-methylpropan-2-yl)oxy)phenyl)azetidine 4-methylbenzenesulfonic acid Step 1: 1-nitro-4-((1,1,1-trifluoro-2-methylpropan-2-yl)oxy)benzene To an ice-cold solution of 1,1,1-trifluoro-2-methylpropan-2-ol (327 mg, 2.55 mmol, 1.2 equiv; CAS RN507-52-8) in DMF (4 mL) was added sodium hydride (102 mg, 2.55 mmol, 1.2 equiv; 55% in mineral oil), and the reaction mixture was stirred at room temperature. After 1 h, 1-fluoro-4-nitrobenzene (300 mg, 2.13 mmol, 1.0 equiv; CAS RN350-46-9) was added portionwise, and stirring was continued at room temperature overnight. The reaction mixture was poured into half-saturated aqueous NH4Cl and EtOAc, and the layers were separated. The aqueous layer was extracted twice with E...

Claims

1. Equation (I) 【Chemistry 1】 (In the formula, R ５ is, 【Chemistry 2】 , C １－６ -alkyl, C １－６ -alkoxy, halo-C １－６ -alkyl, halo-C １－６ -alkoxy, C １－６ -alkyl-SO ２ , C １－６ -alkyl-SO ２ selected from NH-; R １ Hydrogen, halogen, SF ５ , basis 【Transformation 3】 , sulfamoyl, (C １－６ -Alkyl) ２ PO-C １－６ - Alkyl, group 【Chemistry 4】 , cyano, C １－６ - Alkyl, C １－６ - Alkoxy, Halo-C １－６ -Alkyl, Halo-C １－６ - Alkoxy, Carbamoyl, Oxo, C １－６ -Alkyl-NHC(O)-, C １－６ - Alkoxycarbonyl and C １－６ -Alkoxycarbonyl-C １－６ - Alkyl; C ３－１０ - Selected from cycloalkyl; and R ２ These are hydrogen, halogen, cyano, and C １－６ - Alkyl, C １－６ - Alkoxy, Halo-C １－６ -Alkyl, Halo-C １－６ - Alkoxy, and C １－６ - Selected from alkylsulfonyl; or R １ and R ２ Together with the atom(s) to which they are bonded, they form one or more C １－６ - Forms a 3- to 14-membered heterocycle optionally substituted with alkyl substituents; R ２ａ It is selected from hydrogen and halogens; R ３ is hydrogen and C １－６ - Selected from alkyl groups; R ４ is hydrogen, hydroxyl, amino, group 【Transformation 5】 , basis 【Transformation 6】 Sulfamoyl, carboxy, hydroxy-C １－６ - Alkyl, C １－６ -alkyl-SO ２ NH-, Carbamoyl, C １－６ -Alkyl-NHC(O)-, (C １－６ -Alkyl) ２ NC(O)-, C １－６ -Alkyl-C(O)NH-, C １－６ -alkoxy-C(O)NH- and C １－６ Selected from -alkoxy-C(O)-; R ４ａ is hydrogen and C １－６ - Selected from alkyl groups; R ６ is hydrogen, C ６－１４ - Aryl and Halo-C ６－１４ - Selected from the aryl group; R ７ C １－６ -Alkyl, cyano-C １－６ -Alkyl and halo-C １－６ - Selected from alkyl groups; R ８ These are hydrogen, halogen, cyano, hydroxy, oxo, carboxy, C １－６ - Alkoxycarbonyl, C １－６ - Alkyl, group 【Transformation 7】 , basis 【Transformation 8】 , basis 【Chemistry 9】 , C １－６ -alkyl-SO-, C １－６ -alkyl-S-, C １－６ -alkyl-SO ２ -C １－６ - Alkyl, (C １－６ -Alkyl) ２ -PO-, C １－６ - Alkoxy, Halo-C １－６ -Alkyl, Halo-C １－６ - Alkoxy, carbamoyl, and C １－６ Selected from -alkyl-NHC(O)-; R ９ is hydrogen, halogen, hydroxyl, C １－６ -Alkyl and halo-C １－６ - Selected from alkyl groups; R １０ It is selected from hydrogen and halogens; R １１ It is selected from hydrogen, methyl, cyclopropylmethyl, and phenyl; R １２ These are hydrogen, halogens, oxo, and C. １－６ - Alkyl, C １－６ - Alkoxycarbonyl, and C ３－１０ - Selected from cycloalkyl groups; R １３ is hydrogen, C １－６ -Alkyl and halo-C １－６ - Selected from alkyl groups; A is C ６－１４ - Aryl, C ３－１０ - Selected from cycloalkyl, 5-6 membered heteroaryl, and 3-14 membered heterocyclyl; B is azetidinil, piperidil, piperazinil, 2-azaspiro[3.3]heptanil, 2,6-diazaspiro[3.3]heptanil, 2-azaspiro[3.4]octanil, 6-azaspiro[3.4]octanil, 2,7-diazaspiro[3.4]octanil, 2,7-diazaspiro[3.5]nonanil, 2-azaspiro[3.5]nonanil, 7-azaspiro[3.5]nonanil, 1,2,3,3a,4,5,6,6a-octahydrocyclopenta[c]pyrrolyl, cyclobutyl, cubanil, spiro[3.3]heptanil, base 【Chemistry 10】 ; and base 【Chemistry 11】 Selected from; C is selected from phenyl, azetidinyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, 4,5-dihydroisoxazolyl, 2-azabicyclo[2.1.1]hexanyl, 2-azaspiro[3.3]heptanyl, and 2,8-diazaspiro[3.5]nonanyl; D is C ６－１４ - Aryl, C ３－１０ - Selected from cycloalkyl, 5-6 membered heteroaryl, and 3-14 membered heterocyclyl; E is a 5-14 member heteroaryl, a 3-14 member heterocyclyl, and C ３－１０ - Selected from cycloalkyl groups; F is C ３－１０ - Selected from cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 14-membered heteroaryl; L is a covalent bond, a carbonyl, -CHR ６ -, -O-, -NR １１ -, -NHCH ２ -, -CH ２ NR １１ -, -N(CH ３ )CH ２ -, -OCH ２ -, -CH ２ O-, -CH ２ OCH ２ -, -CH ２ CH ２ -, -CF ２ CH ２ -, -CH ２ CF ２ -, -CH=CH-, -C≡C-, -SO ２ -, -SO ２ NH-, -SO ２ NHCH ２ -, -C(O)NH-, -NHCO-, -CH ２ NHCO-, and 【Chemistry 12】 Selected from; L １ is a covalent bond, carbonyl, -CH ２ -ien-CH ２ O-, -OCH ２ -, -NHCH ２ -ien-CH ２ NH-, -NR １１ -, -C(O)-NH-NH-C(O)-CH ２ -, -SO ２ - and -O- are selected; L ２ Covalent and -SO ２ - Selected from; L ３ These are covalent bonds, carbonyl, and -CH ２ - Selected from; X is selected from O and NH; However, if B is 2-azaspiro[3.3]heptanyl or 2,6-diazaspiro[3.3]heptanyl, L is not covalent. Compounds thereof, or pharmaceutically acceptable salts thereof.

2. A compound of formula (I) is a compound of formula (I-I) 【Chemistry 13】 (In the formula, R １ ~R ４ A, B, and L are as defined in claim 1; p and q are independently selected from 0 and 1. A compound according to claim 1, or a pharmaceutically acceptable salt thereof.

3. R ５ is, 【Chemistry 14】 , C １－６ -alkyl-SO ２ -, C １－６ -alkyl-SO ２ NH- and Halo-C １－６ - Selected from alkoxy; R １ Hydrogen, halogen, SF ５ , basis 【Chemistry 15】 , sulfamoyl, (C １－６ -Alkyl) ２ PO-C １－６ - Alkyl, group 【Chemistry 16】 , C １－６ - Alkyl, C １－６ - Alkoxy, Halo-C １－６ -Alkyl, Halo-C １－６ - Alkoxy, Carbamoyl, Oxo, C １－６ -Alkyl-NHC(O)-, C １－６ - Alkoxycarbonyl, and C １－６ -Alkoxycarbonyl-C １－６ - Selected from alkyl groups; and R ２ These are hydrogen, halogen, cyano, and C １－６ - Alkyl, C １－６ - Alkoxy, Halo-C １－６ -Alkyl, Halo-C １－６ - Alkoxy, and C １－６ - Selected from alkylsulfonyl; or R １ and R ２ These, together with the atom(s) they are bonded to, form 1-2 C １－６ - Forms a 3- to 14-membered heterocycle optionally substituted with alkyl substituents; R ２ａ It is selected from hydrogen and halogens; R ６ is hydrogen, C ６－１４ - Aryl and Halo-C ６－１４ - Selected from the aryl group; R ７ C １－６ -Alkyl, cyano-C １－６ -Alkyl and halo-C １－６ - Selected from alkyl groups; R ８ These are hydrogen, halogen, cyano, hydroxy, oxo, carboxy, C １－６ - Alkoxycarbonyl, C １－６ - Alkyl, group 【Chemistry 17】 , basis [Chemistry 18] , basis 【Chemistry 19】 , C １－６ -alkyl-SO-, C １－６ -alkyl-S-, C １－６ -alkyl-SO ２ -C １－６ - Alkyl, (C １－６ -Alkyl) ２ -PO-, C １－６ - Alkoxy, Halo-C １－６ -Alkyl, Halo-C １－６ - Alkoxy, carbamoyl, and C １－６ Selected from -alkyl-NHC(O)-; R ９ is hydrogen, halogen, hydroxyl, C １－６ -Alkyl and halo-C １－６ - Selected from alkyl groups; R １０ It is selected from hydrogen and halogens; R １１ It is selected from hydrogen, methyl, cyclopropylmethyl, and phenyl; R １３ is hydrogen, C １－６ -Alkyl and halo-C １－６ - Selected from alkyl groups; A is C ６－１４ - Aryl, C ３－１０ - Selected from cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 6-membered heteroaryl; D is C ６－１４ - Aryl, C ３－１０ - Selected from cycloalkyl, 5-6 membered heteroaryl, and 3-14 membered heterocyclyl; F is C ３－１０ - Selected from cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 14-membered heteroaryl; LO、shared connection、-CHRR ６ -, -O-, -NR １１ -、-NHCH ２ -、-CH ２ NR １１ -、-OCH ２ -、-CH ２ O-,-CH ２ OCH ２ -、-CH ２ CH ２ -, -CF ２ CH ２ -、-CH ２ CF ２ -、-CH=CH-、-C≡C-、-SO ２ -、-SO ２ NH-,-SO ２ NHCHH ２ -、-C(O)NX-、-NXC(O)-、-CH ２ NFC(O)-、and 【Chemistry 20】 Selected from; L １ is a covalent bond, carbonyl, -CH ２ -ien-CH ２ O-, -NHCH ２ -ien-CH ２ NH-, -NR １１ -, -C(O)-NH-NH-C(O)-CH ２ -, -SO ２ - and -O- are selected; L ３ These are covalent bonds, carbonyl, and -CH ２ - Selected from; X is selected from O and NH. The compound according to claim 1, or a pharmaceutically acceptable salt thereof.

4. R ５ is, 【Chemistry 21】 And; R １ is halogen, C １－６ -Alkyl, Halo-C １－６ - Alkyl, and group 【Chemistry 22】 Selected from; R ２ This includes hydrogen, halogens, and halo-C. １－６ - Selected from alkyl groups; R ２ａ is hydrogen; R ８ and R ９ These are, independently, halogen and halo-C. １－６ - Selected from alkyl groups; R １０ is hydrogen; A is C ６－１４ - Aryl and C ３－１０ - Selected from cycloalkyl groups; D is C ６－１４ - Aryl and C ３－１０ - Selected from cycloalkyl groups; L is a covalent bond, -O- and -CH ２ Selected from O-; L １ It is a covalent bond. The compound according to claim 3, or a pharmaceutically acceptable salt thereof.

5. R ５ is, 【Chemistry 23】 And; R １ Fluorochloroterit-butyl, CHF ２ CF ３ , and base 【Chemistry 24】 Selected from; R ２ These are hydrogen, fluoro, chloro and CF ３ Selected from; R ２ａ is hydrogen; R ８ and R ９ These are, independently, fluoro, chloro, and CF ３ Selected from; R １０ is hydrogen; A is selected from phenyl and cyclopropyl; D is selected from phenyl and cyclopropyl; L is a covalent bond, -O- and -CH ２ Selected from O-; L １ It is a covalent bond. The compound according to claim 4, or a pharmaceutically acceptable salt thereof.

6. B is selected from spiro[3.3]heptan-2-yl, azetidinil, and 7-azaspiro[3.5]nonan-7-yl; R ３ It is hydrogen. The compound according to claim 1, or a pharmaceutically acceptable salt thereof.

7. R ４ is, 【Chemistry 25】 and selected from carbamoyl; R ４ａ is hydrogen; R １２ It is selected from hydrogen and oxo; C is pyrrolidinyl; E is selected from five-membered heteroaryls and five-membered heterocyclines; L ２ It is a covalent bond. The compound according to claim 1, or a pharmaceutically acceptable salt thereof.

8. R ４ is, 【Chemistry 26】 and selected from carbamoyl; R ４ａ is hydrogen; R １２ It is selected from hydrogen and oxo; C is pyrrolidinyl; E is selected from imidazolyl, pyrazolyl, triazolyl, and oxazolidinil; L ２ It is a covalent bond. The compound according to claim 7, or a pharmaceutically acceptable salt thereof.

9. R ５ is, 【Chemistry 27】 , C １－６ -alkyl-SO ２ -, C １－６ -alkyl-SO ２ NH- and Halo-C １－６ - Selected from alkoxy; R １ Hydrogen, halogen, SF ５ , basis 【Chemistry 28】 , sulfamoyl, (C １－６ -Alkyl) ２ PO-C １－６ - Alkyl, group 【Chemistry 29】 , C １－６ - Alkyl, C １－６ - Alkoxy, Halo-C １－６ -Alkyl, Halo-C １－６ - Alkoxy, Carbamoyl, Oxo, C １－６ -Alkyl-NHC(O)-, C １－６ - Alkoxycarbonyl, and C １－６ -Alkoxycarbonyl-C １－６ - Selected from alkyl groups; and R ２ These are hydrogen, halogen, cyano, and C １－６ - Alkyl, C １－６ - Alkoxy, Halo-C １－６ -Alkyl, Halo-C １－６ - Alkoxy, and C １－６ - Selected from alkylsulfonyl; or R １ and R ２ These, together with the atom(s) they are bonded to, form 1-2 C １－６ - Forms a 3- to 14-membered heterocycle optionally substituted with alkyl substituents; R ２ａ It is selected from hydrogen and halogens; R ３ is hydrogen and C １－６ - Selected from alkyl groups; R ４ is hydrogen, hydroxyl, amino, group 【Transformation 30】 , basis 【Chemistry 31】 Sulfamoyl, carboxy, hydroxy-C １－６ - Alkyl, C １－６ -alkyl-SO ２ NH-, Carbamoyl, C １－６ -Alkyl-NHC(O)-, (C １－６ -Alkyl) ２ NC(O)-, C １－６ -Alkyl-C(O)NH-, C １－６ -alkoxy-C(O)NH- and C １－６ Selected from -alkoxy-C(O)-; R ４ａ is hydrogen and C １－６ - Selected from alkyl groups; R ６ is hydrogen, C ６－１４ - Aryl and Halo-C ６－１４ - Selected from the aryl group; R ７ C １－６ -Alkyl, cyano-C １－６ -Alkyl and halo-C １－６ - Selected from alkyl groups; R ８ These are hydrogen, halogen, cyano, hydroxy, oxo, carboxy, C １－６ - Alkoxycarbonyl, C １－６ - Alkyl, group 【Chemistry 32】 , basis 【Transformation 33】 , basis 【Transformation 34】 , C １－６ -alkyl-SO-, C １－６ -alkyl-S-, C １－６ -alkyl-SO ２ -C １－６ - Alkyl, (C １－６ -Alkyl) ２ -PO-, C １－６ - Alkoxy, Halo-C １－６ -Alkyl, Halo-C １－６ - Alkoxy, carbamoyl, and C １－６ Selected from -alkyl-NHC(O)-; R ９ is hydrogen, halogen, hydroxyl, C １－６ -Alkyl and halo-C １－６ - Selected from alkyl groups; R １０ It is selected from hydrogen and halogens; R １１ It is selected from hydrogen, methyl, cyclopropylmethyl, and phenyl; R １２ These are hydrogen, halogens, oxo, and C. １－６ - Alkyl, C １－６ - Alkoxycarbonyl, and C ３－１０ - Selected from cycloalkyl groups; R １３ is hydrogen, C １－６ -Alkyl and halo-C １－６ - Selected from alkyl groups; A is C ６－１４ - Aryl, C ３－１０ - Selected from cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 6-membered heteroaryl; B is azetidinil, piperidil, piperazinil, 2-azaspiro[3.3]heptanil, 2,6-diazaspiro[3.3]heptanil, 2-azaspiro[3.4]octanil, 6-azaspiro[3.4]octanil, 2,7-diazaspiro[3.4]octanil, 2,7-diazaspiro[3.5]nonanil, 2-azaspiro[3.5]nonanil, 7-azaspiro[3.5]nonanil, 1,2,3,3a,4,5,6,6a-octahydrocyclopenta[c]pyrrolyl, cyclobutyl, cubanil, spiro[3.3]heptanil, base 【Chemistry 35】 ; and base 【Transformation 36】 Selected from; C is selected from phenyl, azetidinyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, 4,5-dihydroisoxazolyl, 2-azabicyclo[2.1.1]hexanyl, 2-azaspiro[3.3]heptanyl, and 2,8-diazaspiro[3.5]nonanyl; D is C ６－１４ - Aryl, C ３－１０ - Selected from cycloalkyl, 5-6 membered heteroaryl, and 3-14 membered heterocyclyl; E is a 5-14 member heteroaryl, a 3-14 member heterocyclyl, and C ３－１０ - Selected from cycloalkyl groups; F is C ３－１０ - Selected from cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 14-membered heteroaryl; LO、shared connection、-CHRR ６ -, -O-, -NR １１ -、-NHCH ２ -、-CH ２ NR １１ -、-OCH ２ -、-CH ２ O-,-CH ２ OCH ２ -、-CH ２ CH ２ -, -CF ２ CH ２ -、-CH ２ CF ２ -、-CH=CH-、-C≡C-、-SO ２ -、-SO ２ NH-,-SO ２ NHCHH ２ -、-C(O)NX-、-NXC(O)-、-CH ２ NFC(O)-、and 【Chemistry 37】 Selected from; L １ is a covalent bond, carbonyl, -CH ２ -ien-CH ２ O-, -NHCH ２ -ien-CH ２ NH-, -NR １１ -, -C(O)-NH-NH-C(O)-CH ２ -, -SO ２ - and -O- are selected; L ２ Covalent and -SO ２ - Selected from; L ３ These are covalent bonds, carbonyl, and -CH ２ - Selected from; X is selected from O and NH. The compound according to claim 1, or a pharmaceutically acceptable salt thereof.

10. R ５ is, 【Transformation 38】 And; R １ is halogen, C １－６ -Alkyl, Halo-C １－６ - Alkyl, and group 【Chemistry 39】 Selected from; R ２ This includes hydrogen, halogens, and halo-C. １－６ - Selected from alkyl groups; R ２ａ is hydrogen; R ３ is hydrogen; R ４ is, 【Chemistry 40】 and selected from carbamoyl; R ４ａ is hydrogen; R ８ and R ９ These are, independently, halogen and halo-C. １－６ - Selected from alkyl groups; R １０ is hydrogen; R １２ It is selected from hydrogen and oxo; A is C ６－１４ - Aryl and C ３－１０ - Selected from cycloalkyl groups; B is selected from spiro[3.3]heptan-2-yl, azetidinyl, and 7-azaspiro[3.5]nonane-7-yl; C is pyrrolidinyl; D is C ６－１４ - Aryl and C ３－１０ - Selected from cycloalkyl groups; E is selected from five-membered heteroaryls and five-membered heterocyclines; L is a covalent bond, -O- and -CH ２ Selected from O-; L １ It is a covalent bond; L ２ It is a covalent bond. The compound according to claim 9, or a pharmaceutically acceptable salt thereof.

11. R ５ is, 【Chemistry 41】 And; R １ Fluorochloroterit-butyl, CHF ２ CF ３ , and base 【Chemistry 42】 Selected from; R ２ These are hydrogen, fluoro, chloro and CF ３ Selected from; R ２ａ is hydrogen; R ３ is hydrogen; R ４ is, 【Chemistry 43】 and selected from carbamoyl; R ４ａ is hydrogen; R ８ and R ９ These are, independently, fluoro, chloro, and CF ３ Selected from; R １０ is hydrogen; R １２ It is selected from hydrogen and oxo; A is selected from phenyl and cyclopropyl; B is selected from spiro[3.3]heptan-2-yl, azetidinyl, and 7-azaspiro[3.5]nonane-7-yl; C is pyrrolidinyl; D is selected from phenyl and cyclopropyl; E is selected from imidazolyl, pyrazolyl, triazolyl, and oxazolidinil; L is a covalent bond, -O- and -CH ２ Selected from O-; L １ It is a covalent bond; L ２ It is a covalent bond. The compound according to claim 10, or a pharmaceutically acceptable salt thereof.

12. The compound of formula (I) is [3-[[2-fluoro-6-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; 4-[1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-yl]oxazolidine-2-one; (+)- or (-)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; (-)- or (+)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(4-methyl-1H-pyrazole-5-yl)azetidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-pyrazole-5-yl)azetidine-1-yl]methanone; [4-[(2-chloro-4-fluorophenyl)methoxy]-1-piperidyl]-[3-(4-methyl-1H-pyrazole-5-yl)azetidine-1-yl]methanone; [4-[(4-chloro-2-fluorophenoxy)methyl]-1-piperidyl]-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-pyrazole-5-yl)-1-piperidyl]methanone; [6-(2-chloro-4-fluorophenoxy)-2-azaspiro[3.3]heptan-2-yl]-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; [3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]-[4-[[4-(trifluoromethyl)phenyl]methyl]-1-piperidyl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(2-methylpyrazole-3-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-pyrazole-5-yl)phenyl]methanone; [3-[[2-fluoro-4-(pentafluoro-λ ６ -Sulfanyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; (+)- or (-)-[3-[[2-fluoro-6-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; (-)- or (+)-[3-[[2-fluoro-6-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-(2,4-dichlorophenyl)phenyl]azetidine-1-yl]-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; 6-[1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-yl]-1H-pyridine-2-one; 6-[1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-yl]-1H-pyrazine-2-one; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(4-isopropyl-1H-pyrazole-3-yl)pyrrolidine-1-yl]methanone; 4-[1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-yl]oxazolidine-2-one; Ethyl 5-[1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-yl]-1H-pyrazole-4-carboxylate; 5-[1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-yl]pyrrolidine-2-one; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[(3R)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; 1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-yl]methanone; [3-(4-tert-butylphenyl)azetidine-1-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1,2,4-triazole-1-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-(3-imidazole-1-ylpyrrolidine-1-yl)methanone; [3-[[2,4-bis(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (+)- or (-)-[2-(2-chloro-4-fluorophenoxy)-7-azaspiro[3.5]nonan-7-yl]-[(3R)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (-)- or (+)-[2-(2-chloro-4-fluorophenoxy)-7-azaspiro[3.5]nonan-7-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (+)- or (-)-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]-[3-(4-tetrahydropyran-4-ylphenyl)azetidine-1-yl]methanone; (-)- or (+)-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]-[3-(4-tetrahydropyran-4-ylphenyl)azetidine-1-yl]methanone; (+)- or (-)-[3-(4-isopropoxyphenyl)azetidine-1-yl]-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; (-)- or (+)-[3-(4-isopropoxyphenyl)azetidine-1-yl]-[(3S)-3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; (+)- or (-)-[6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (-)- or (+)-[6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-imidazole-5-yl)pyrrolidine-1-yl]methanone; (+)- or (-)-[2-[2-fluoro-4-(trifluoromethyl)phenoxy]-7-azaspiro[3.5]nonan-7-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (-)- or (+)-[2-[2-fluoro-4-(trifluoromethyl)phenoxy]-7-azaspiro[3.5]nonan-7-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-imidazole-2-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; Sodium [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[rac-(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[(3R)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; (+)- or (-)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-imidazole-1-ylpyrrolidine-1-yl]methanone; (-)- or (+)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-imidazole-1-ylpyrrolidine-1-yl]methanone; [3-[[3-chloro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-chloro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (+)- or (-)-[3-[2-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl]azetidine-1-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (-)- or (+)-[3-[2-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl]azetidine-1-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (+)- or (-)-[3-(4-propoxyphenyl)azetidine-1-yl]-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; (-)- or (+)-[3-(4-propoxyphenyl)azetidine-1-yl]-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; (+)- or (-)-[3-[[2,4-bis(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (-)- or (+)-[3-[[2,4-bis(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-tetrazole-5-yl)pyrrolidine-1-yl]methanone; (+)- or (-)-1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]-N-methyl-pyrrolidine-3-carboxamide; (-)- or (+)-1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]-N-methyl-pyrrolidine-3-carboxamide; (+)- or (-)-1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]-N,N-dimethyl-pyrrolidine-3-carboxamide; (-)- or (+)-1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]-N,N-dimethyl-pyrrolidine-3-carboxamide; (+)- or (-)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-pyrazole-1-ylpyrrolidine-1-yl]methanone; (-)- or (+)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-pyrazole-1-ylpyrrolidine-1-yl]methanone; (+)- or (-)-1-[3-[4-(2,4-difluorophenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (-)- or (+)-1-[3-[4-(2,4-difluorophenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]-[3-(4-tetrahydrofuran-3-ylphenyl)azetidine-1-yl]methanone; [3-(4-tert-butylphenyl)azetidine-1-yl]-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; [3-[2-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl]azetidine-1-yl]-[(3S)-3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(triazole-1-yl)pyrrolidine-1-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; [3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]-[3-(4-tetrahydropyran-3-ylphenyl)azetidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-(3-pyrrole-1-ylpyrrolidine-1-yl)methanone; trans-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]cyclobutyl]-[3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; (+)- or (-)-[3-[4-[(1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl]phenyl]azetidine-1-yl]-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; (-)- or (+)-[3-[4-[(1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl]phenyl]azetidine-1-yl]-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; (-)- or (+)-[3-[4-(2,4-difluorophenyl)phenyl]azetidine-1-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (+)- or (-)-[3-[4-(2,4-difluorophenyl)phenyl]azetidine-1-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-(2,4-difluorophenyl)phenyl]azetidine-1-yl]-[(3S)-3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; [4-[bis(4-fluorophenyl)methyl]-1-piperidyl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; 4-[1-[3-[3-chloro-4-(trifluoromethoxy)phenyl]azetidine-1-carbonyl]pyrrolidine-3-yl]oxazolidine-2-one; [3-[4-(2-methylazetidine-1-yl)phenyl]azetidine-1-yl]-[(3S or 3R)-3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-(2-methylazetidine-1-yl)phenyl]azetidine-1-yl]-[(3R or 3S)-3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-(3-fluoropyrrolidine-1-yl)phenyl]azetidine-1-yl]-[(3R or 3S)-3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; (+)- or (-)-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-yl]methanone; (-)- or (+)-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-yl]methanone; (+)- or (-)-[3-[[2-chloro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (-)- or (+)-[3-[[2-chloro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-(3-fluoropyrrolidine-1-yl)phenyl]azetidine-1-yl]-[(3S or 3R)-3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; 4-[1-[3-[4-(2,2,2-trifluoroethyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-yl]oxazolidine-2-one; [3-[4-(oxetan-3-yl)phenyl]azetidine-1-yl]-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; (+)- or (-)-[3-[4-(oxetan-3-yl)phenyl]azetidine-1-yl]-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; (-)- or (+)-[3-[4-(oxetan-3-yl)phenyl]azetidine-1-yl]-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; 4-[1-[3-[4-(2,4-difluorophenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-yl]oxazolidine-2-one; [3-(1H-triazole-5-yl)pyrrolidine-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-yl]methanone; [4-[bis(4-fluorophenyl)methyl]-1-piperidyl]-[3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; 4-[1-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-yl]oxazolidine-2-one; (+)- or (-)-[3-(1H-triazole-5-yl)pyrrolidine-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-yl]methanone; (-)- or (+)-[3-(1H-triazole-5-yl)pyrrolidine-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-yl]methanone; (+)- or (-)-[3-(3,3-dimethyl-2H-benzofuran-6-yl)azetidine-1-yl]-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; (-)- or (+)-[3-(3,3-dimethyl-2H-benzofuran-6-yl)azetidine-1-yl]-[3-(1H-pyrazole-5-yl)pyrrolidine-1-yl]methanone; (+)- or (-)-[4-[bis(4-fluorophenyl)methyl]-1-piperidyl]-[3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; (-)- or (+)-[4-[bis(4-fluorophenyl)methyl]-1-piperidyl]-[3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-chloro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]-[3-[4-(2,2,2-trifluoro-1,1-dimethylethoxy)phenyl]azetidine-1-yl]methanone; [3-[[2-fluoro-4-(pentafluoro-λ ６ -Sulfanyl)phenyl]methoxy]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; (+)-[4-[(2-chloro-4-fluoro-phenoxy)methyl]-1-piperidyl]-[(3R)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; (-)-[4-[(2-chloro-4-fluoro-phenoxy)methyl]-1-piperidyl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; (+)- or (-)-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[3-[4-(2,2,2-trifluoro-1,1-dimethylethoxy)phenyl]azetidine-1-yl]methanone; (-)- or (+)-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[3-[4-(2,2,2-trifluoro-1,1-dimethylethoxy)phenyl]azetidine-1-yl]methanone; (+)- or (-)-[4-[[2-chloro-4-(trifluoromethyl)phenyl]methoxy]-1-piperidyl]-[(3R)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; (-)- or (+)-[4-[[2-chloro-4-(trifluoromethyl)phenyl]methoxy]-1-piperidyl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3R or 3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]-[3-[[4-(trifluoromethyl)phenyl]methyl]pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]-8-azabicyclo[3.2.1]octan-8-yl]-[(3R or 3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]-8-azabicyclo[3.2.1]octan-8-yl]-[(3S or 3R)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3aS,6aR)-5-[2-fluoro-4-(trifluoromethyl)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]-[(3R or 3S)-3-(1H-triazole-5-yl)pyrroridine-1-yl]methanone; [(3aS,6aR)-5-[2-fluoro-4-(trifluoromethyl)phenoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-yl]-[(3S or 3R)-3-(1H-triazole-5-yl)pyrroridine-1-yl]methanone; (-)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidine-1-yl]-[(3R or 3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; (+)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidine-1-yl]-[(3R or 3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; (-)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidine-1-yl]-[(3R or 3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; (+)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidine-1-yl]-[(3S or 3R)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; (-)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidine-1-yl]-[(3S or 3R)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; (+)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidine-1-yl]-[(3S or 3R)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[6-(2-chlorophenoxy)-3-pyridyl]azetidine-1-yl]-[3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[(3S)-3-(1,2,4-triazole-4-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[(3R)-3-(1,2,4-triazole-4-yl)pyrrolidine-1-yl]methanone; [3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[3-[4-[3-(2,2,2-trifluoroethoxy)azetidine-1-yl]phenyl]azetidine-1-yl]methanone; [6-(2-chloro-4-fluorophenoxy)-2-azaspiro[3.3]heptan-2-yl]-[3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridyl]azetidine-1-yl]methanone; [(3S)-3-(1,2,4-triazole-4-yl)pyrroridine-1-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazole-3-yl]azetidine-1-yl]methanone; [(3S)-3-(1,2,4-triazole-4-yl)pyrroridine-1-yl]-[3-[4-[3-(2,2,2-trifluoroethoxy)azetidine-1-yl]phenyl]azetidine-1-yl]methanone; [6-(2-chloro-4-fluorophenoxy)-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1,2,4-triazole-4-yl)pyrrolidine-1-yl]methanone; [(3R)-3-(1,2,4-triazole-4-yl)pyrroridine-1-yl]-[6-[6-(trifluoromethyl)pyrazine-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; [(3R)-3-(1,2,4-triazole-4-yl)pyrroridine-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridyl]azetidine-1-yl]methanone; [3-[4-(4-fluorophenoxy)phenyl]azetidine-1-yl]-[3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [3-(tetrazole-1-yl)pyrroridine-1-yl]-[6-[6-(trifluoromethyl)pyrazine-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; [3-(tetrazole-1-yl)pyrroridine-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridyl]azetidine-1-yl]methanone; (+)- or (-)-[3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]-[3-[4-[3-(2,2,2-trifluoroethoxy)azetidine-1-yl]phenyl]azetidine-1-yl]methanone; (-)- or (+)-[3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]-[3-[4-[3-(2,2,2-trifluoroethoxy)azetidine-1-yl]phenyl]azetidine-1-yl]methanone; (+)- or (-)-[6-(2-chloro-4-fluorophenoxy)-2-azaspiro[3.3]heptan-2-yl]-[3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; (-)- or (+)-[6-(2-chloro-4-fluorophenoxy)-2-azaspiro[3.3]heptan-2-yl]-[3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; (+)- or (-)-[3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridyl]azetidine-1-yl]methanone; (-)- or (+)-[3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridyl]azetidine-1-yl]methanone; (+)- or (-)-[3-[4-(4-fluorophenoxy)phenyl]azetidine-1-yl]-[3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; (-)- or (+)-[3-[4-(4-fluorophenoxy)phenyl]azetidine-1-yl]-[3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; (+)- or (-)-[3-(tetrazole-1-yl)pyrrolidine-1-yl]-[6-[6-(trifluoromethyl)pyrazine-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; (-)- or (+)-[3-(tetrazole-1-yl)pyrrolidine-1-yl]-[6-[6-(trifluoromethyl)pyrazine-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; (+)- or (-)-[3-(tetrazole-1-yl)pyrrolidine-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridyl]azetidine-1-yl]methanone; (-)- or (+)-[3-(tetrazole-1-yl)pyrrolidine-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridyl]azetidine-1-yl]methanone; [(3R)-3-(1H-triazole-5-yl)pyrroridine-1-yl]-[2-(3,3,3-trifluoropropoxy)spiro[3,3]heptan-6-yl]methanone; [(3R)-3-(1H-triazole-5-yl)pyrroridine-1-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazole-3-yl]azetidine-1-yl]methanone; [3-[4-(4-fluorophenoxy)phenyl]azetidine-1-yl]-[(3R)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3R)-3-(1H-triazole-5-yl)pyrroridine-1-yl]-[3-[4-[3-(2,2,2-trifluoroethoxy)azetidine-1-yl]phenyl]azetidine-1-yl]methanone; [6-(2-chloro-4-fluorophenoxy)-2-azaspiro[3.3]heptan-2-yl]-[(3R)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3R)-3-(1H-triazole-5-yl)pyrroridine-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridyl]azetidine-1-yl]methanone; [(3R)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]-[3-[6-[3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-yl]methanone; [3-[2-(3-chlorophenyl)ethinyl]azetidine-1-yl]-[(3R)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[2-[2-(difluoromethyl)phenyl]ethynyl]azetidine-1-yl]-[(3R)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [4-(3-cyclopropyl-1,2,4-oxadiazole-5-yl)piperazine-1-yl]-[rac-(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-[3-chloro-5-(2,2,2-trifluoroethoxy)phenoxy]pyrrolidine-1-yl]-[(3S or 3R)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-[3-chloro-5-(2,2,2-trifluoroethoxy)phenoxy]pyrrolidine-1-yl]-[(3R or 3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3R)-3-[3-chloro-5-(2,2,2-trifluoroethoxy)phenoxy]pyrrolidine-1-yl]-[(3S or 3R)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3R)-3-[3-chloro-5-(2,2,2-trifluoroethoxy)phenoxy]pyrrolidine-1-yl]-[(3R or 3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]-[2-(3,3,3-trifluoropropoxy)spiro[3,3]heptan-6-yl]methanone; [2-[[1-(difluoromethyl)cyclopropyl]methoxy]spiro[3.3]heptan-6-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [8-(3-cyclopropyl-1,2,4-oxadiazole-5-yl)-8-azabicyclo[3.2.1]octan-3-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[3-(triazole-1-yl)pyrrolidine-1-yl]methanone; [3-[4-[3-(2,2-dimethylpropyl)triazole-4-yl]phenyl]azetidine-1-yl]-[3-(triazole-1-yl)pyrrolidine-1-yl]methanone; [3-(triazole-1-yl)pyrrolidine-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-yl]methanone; [3-(2-chloro-4-isopropylsulfonylphenyl)azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-(4-tert-butylsulfonyl-2-chlorophenyl)azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[5-(2-chlorophenoxy)pyrazine-2-yl]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-triazole-5-yl)pyrroridine-1-yl]-[6-[6-(trifluoromethyl)pyrazine-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-triazole-5-yl)pyrroridine-1-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazole-3-yl]azetidine-1-yl]methanone; [3-[6-(2,4-dichlorophenoxy)-3-pyridyl]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-(4-fluorophenoxy)phenyl]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-(2-chloro-4-isobutylsulfonylphenyl)azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-(benzenesulfonyl)phenyl]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-(2-chloro-4-propylsulfonylphenyl)azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-(2-chloro-4-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-(4-tert-butylphenyl)azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; 1-[3-[4-(2-chloro-4-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-(5-tert-butyl-2-pyridyl)azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; 1-[3-[4-(2-chloro-4-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxylic acid; 1-[3-[4-(2,4-difluorophenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxylic acid; 2-[4-[1-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]phenyl]sulfonylacetonitrile; [3-[4-(N-methylanilino)phenyl]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]-[3-[4-(trifluoromethylsulfonyl)phenyl]azetidine-1-yl]methanone; [3-(4-cyclohexylsulfonylphenyl)azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; 1-[5-[1-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]-2-pyridyl]cyclobutanecarbonitride; [6-[(2,4-difluorophenyl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [6-[[4-fluoro-2-(trifluoromethyl)phenyl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-[N-(cyclopropylmethyl)anilino]phenyl]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; 1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(N-phenylanilino)phenyl]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-(6-tert-butyl-3-pyridyl)azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[6-[(5-methoxy-2-pyridyl)-methyl-amino]-3-pyridyl]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[6-[(5-ethyl-2-pyridyl)-methyl-amino]-3-pyridyl]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[6-[(5-cyclopropyl-2-pyridyl)-methyl-amino]-3-pyridyl]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-(N-methylanilino)phenyl]azetidine-1-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[6-(N-methylanilino)-3-pyridyl]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[6-(4-isopropyl-N-methyl-anilino)-3-pyridyl]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[6-[(3-ethyl-2-pyridyl)-methyl-amino]-3-pyridyl]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[6-[N-(cyclopropylmethyl)anilino]-3-pyridyl]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; (3S)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3R)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[6-[N-(cyclopropylmethyl)anilino]-3-pyridyl]azetidine-1-yl]-[3-(1H-tetrazole-5-yl)pyrrolidine-1-yl]methanone; [3-(1H-tetrazole-5-yl)pyrrolidine-1-yl]-[3-[4-(2,2,2-trifluoro-1,1-dimethylethoxy)phenyl]azetidine-1-yl]methanone; [2-(2-methoxyphenyl)sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [2-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [2-(2,2-dimethylpropylsulfonyl)-2,6-diazaspiro[3.3]heptan-6-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [2-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]-[(3R)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [2-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [3-[6-[N-(cyclopropylmethyl)anilino]-3-pyridyl]azetidine-1-yl]-[(3S)-3-(1H-tetrazole-5-yl)pyrrolidine-1-yl]methanone; [3-[6-[N-(cyclopropylmethyl)anilino]-3-pyridyl]azetidine-1-yl]-[(3R)-3-(1H-tetrazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-(4-fluorophenoxy)phenyl]azetidine-1-yl]-[3-(1H-tetrazole-5-yl)pyrrolidine-1-yl]methanone; 1-[3-[6-[N-(cyclopropylmethyl)anilino]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(4-fluorophenoxy)phenyl]azetidine-1-yl]-[(3R)-3-(1H-tetrazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-(4-fluorophenoxy)phenyl]azetidine-1-yl]-[(3S)-3-(1H-tetrazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1,2,4-triazole-4-yl)pyrrolidine-1-yl]-[3-[4-[4-(trifluoromethyl)pyrimidine-2-yl]oxyphenyl]azetidine-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[3-(1H-tetrazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1,2,4-triazole-4-yl)pyrroridine-1-yl]-[6-[6-(trifluoromethyl)pyrazine-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1,2,4-triazole-4-yl)pyrroridine-1-yl]-[6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-2-azaspiro[3.3]heptan-2-yl]methanone; (3S)-1-[3-[6-[N-(cyclopropylmethyl)anilino]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3R)-1-[3-[6-[N-(cyclopropylmethyl)anilino]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [6-[[4-fluoro-2-(trifluoromethyl)phenyl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]-[3-[4-[3-(trifluoromethyl)azetidine-1-yl]phenyl]azetidine-1-yl]methanone; 1-[3-[4-(benzenesulfonyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [2-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonan-7-yl]-[3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; 1-[3-[4-[3-(2,2,2-trifluoroethoxy)azetidine-1-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [2-[(2-chloro-4-fluorophenyl)methyl]-2,7-diazaspiro[3.5]nonan-7-yl]-[3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [3-[(2-fluoro-4-methylsulfonylphenyl)methoxy]azetidine-1-yl]-[3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; 1-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; 1-[3-[4-[3-(trifluoromethyl)azetidine-1-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[(3R)-3-(1H-tetrazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[(3S)-3-(1H-tetrazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[(3S)-3-(1,2,4-triazole-4-yl)pyrrolidine-1-yl]methanone; [6-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[3-[[6-(trifluoromethyl)-3-pyridyl]methoxy]azetidine-1-yl]methanone; [3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[3-[[5-(trifluoromethyl)-3-pyridyl]methoxy]azetidine-1-yl]methanone; [3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[6-[[5-(trifluoromethyl)-3-pyridyl]oxy]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-chloro-3-pyridyl)oxy]-2-azaspiro[3.3]heptan-2-yl]-[3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [6-[(6-chloro-3-pyridyl)oxy]-2-azaspiro[3.3]heptan-2-yl]-[3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; (3S)-1-[3-[4-[3-(2,2,2-trifluoroethoxy)azetidine-1-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3R)-1-[3-[4-[3-(2,2,2-trifluoroethoxy)azetidine-1-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-(benzenesulfonyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3R)-1-[3-[4-(benzenesulfonyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[(2-fluoro-4-methylsulfonylphenyl)methoxy]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; 2-Cyclopropyl-6-[1-[(3S)-3-(1,2,4-triazole-4-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]oxy-benzonitrile; (3S)-1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[2-[2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3,3]heptane-6-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[[[3-(trifluoromethyl)phenyl]sulfonylamino]methyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[[[4-(trifluoromethyl)phenyl]sulfonylamino]methyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[6-(trifluoromethyl)-3-pyridyl]oxy]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2,6-diazaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[[6-(trifluoromethyl)-3-pyridyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[[5-(trifluoromethyl)-3-pyridyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[[1-(trifluoromethyl)cyclopropyl]amino]methyl]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(3-chloropyridazine-4-yl)oxyphenyl]azetidine-1-yl]-[(3R)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [3-[(2-fluoro-4-methylsulfonylphenyl)methoxy]azetidine-1-yl]-[(3S)-3-(1,2,4-triazole-4-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1,2,4-triazole-4-yl)pyrroridine-1-yl]-[2-[2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; 1-[4-[1-[(3S)-3-(1,2,4-triazole-4-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]phenyl]cyclopropanecarbonitric; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[(3S)-3-(1,2,4-triazole-4-yl)pyrrolidine-1-yl]methanone; N-[2-[(3S)-3-(1,2,4-triazole-4-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptan-6-yl]-1-(trifluoromethyl)cyclopropanecarboxamide; [(3S)-3-(1,2,4-triazole-4-yl)pyrrolidine-1-yl]-[3-[4-[[1-(trifluoromethyl)cyclopropyl]methylamino]phenyl]azetidine-1-yl]methanone; (3S)-1-[3-[2-[1-(trifluoromethyl)cyclopropyl]pyrimidine-5-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[6-[1-(trifluoromethyl)cyclopropyl]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[3-[[2-(trifluoromethyl)pyrimidine-5-yl]methoxy]azetidine-1-yl]methanone; 1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-N-methyl-pyrrolidine-3-carboxamide; 1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-N-ethyl-pyrrolidine-3-carboxamide; (3S)-1-[3-[4-[[1-(trifluoromethyl)cyclopropyl]amino]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-[[1-(trifluoromethyl)cyclopropyl]methylamino]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[(2-fluoro-4-methylsulfonyl-phenyl)methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[2-(2,4-difluorophenyl)sulfonyl-2,6-diazaspiro[3,3]heptane-6-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[2-[3-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptane-6-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[2-[3-(trifluoromethoxy)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptane-6-carbonyl]pyrrolidine-3-carboxamide; rac-(3S)-1-[3-[5-[3-(trifluoromethyl)pyrrolidine-1-yl]-2-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-N-methyl-pyrrolidine-3-carboxamide; (3R)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-N-methyl-pyrrolidine-3-carboxamide; (3S)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-N-ethyl-pyrrolidine-3-carboxamide; (3R)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-N-ethyl-pyrrolidine-3-carboxamide; [3-[6-(2-chlorophenoxy)-3-pyridyl]azetidine-1-yl]-[(3R)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [3-[4-(4-fluorophenoxy)phenyl]azetidine-1-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [3-[5-(2-chlorophenoxy)pyrazine-2-yl]azetidine-1-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [(3R)-3-(tetrazole-1-yl)pyrroridine-1-yl]-[6-[6-(trifluoromethyl)pyrazine-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; 2-Cyclopropyl-6-[1-[(3R)-3-(tetrazole-1-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]oxybenzonitrile; [3-[5-(2-chlorophenoxy)pyrazine-2-yl]azetidine-1-yl]-[(3R)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(tetrazole-1-yl)pyrroridine-1-yl]-[6-[6-(trifluoromethyl)pyrazine-2-yl]oxy-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[4-[3-(2,2-dimethylpropyl)triazole-4-yl]phenyl]azetidine-1-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [3-[4-(4-fluorophenoxy)phenyl]azetidine-1-yl]-[(3R)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [3-[5-(2,4-dichlorophenoxy)pyrazine-2-yl]azetidine-1-yl]-[(3R)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; 2-Cyclopropyl-6-[1-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]oxy-benzonitrile; Methyl 2,2-dimethyl-3-[3-[1-[(3R)-3-(tetrazole-1-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]oxyphenyl]propanoate; [3-[6-(2-chlorophenoxy)-3-pyridyl]azetidine-1-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [3-[4-(4-cyclopropylpyrimidine-2-yl)oxyphenyl]azetidine-1-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [3-[5-(2,4-dichlorophenoxy)pyrazine-2-yl]azetidine-1-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; 1-[4-[1-[(3R)-3-(tetrazole-1-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]phenyl]cyclopropanecarbonitric; [3-[4-(4-cyclopropylpyrimidine-2-yl)oxyphenyl]azetidine-1-yl]-[(3R)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; 1-[4-[1-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]phenyl]cyclopropanecarbonitric; Methyl 2,2-dimethyl-3-[3-[1-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]oxyphenyl]propanoate; [3-[4-[3-(2,2-dimethylpropyl)triazole-4-yl]phenyl]azetidine-1-yl]-[(3R)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[(3R)-3-hydroxypyrrolidine-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[(3R)-3-(hydroxymethyl)pyrrolidine-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[(3S)-3-(hydroxymethyl)pyrrolidine-1-yl]methanone; (3S)-1-[6-[[5-(trifluoromethyl)pyrazine-2-yl]methyl]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; [7-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]-[3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [7-[2-fluoro-4-(trifluoromethyl)phenoxy]-2-azaspiro[3.5]nonan-2-yl]-[3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [6-[2-fluoro-4-(trifluoromethyl)anilino]-2-azaspiro[3.3]heptan-2-yl]-[3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [6-[[2-fluoro-4-(trifluoromethyl)phenyl]methylamino]-2-azaspiro[3.3]heptan-2-yl]-[3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; (3S)-1-[3-[4-[3-(methylsulfonylmethyl)azetidine-1-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; rac-(3S)-1-[3-[5-[3-(trifluoromethyl)pyrrolidine-1-yl]pyrazine-2-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [(3S)-3-(1,2,4-triazole-4-yl)pyrrolidine-1-yl]-[3-[4-[3-(trifluoromethyl)azetidine-1-yl]phenyl]azetidine-1-yl]methanone; [6-[[2-fluoro-4-(trifluoromethyl)phenyl]methylamino]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1,2,4-triazole-4-yl)pyrrolidine-1-yl]methanone; [6-[(4,4-difluoro-1-piperidyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [3-[(4,4-difluorocyclohexyl)methoxy]azetidine-1-yl]-[3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; N-[2-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3,3]heptan-6-yl]-1-(trifluoromethyl)cyclopropanecarboxamide; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[3-[4-[[1-(trifluoromethyl)cyclopropyl]amino]phenyl]azetidine-1-yl]methanone; 1-[4-[1-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]phenyl]cyclopropanecarbonitric; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[3-[6-[1-(trifluoromethyl)cyclopropyl]-3-pyridyl]azetidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[3-[2-[1-(trifluoromethyl)cyclopropyl]pyrimidine-5-yl]azetidine-1-yl]methanone; [3-[(2-fluoro-4-methylsulfonylphenyl)methoxy]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[6-[[6-(trifluoromethyl)-3-pyridyl]oxy]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[2-[2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[2-[3-(trifluoromethoxy)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; N-methyl-2-[[2-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-2,6-diazaspiro[3.3]heptan-6-yl]methyl]benzamide; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[2-[3-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [(3S)-3-(1,2,4-triazole-4-yl)pyrroridine-1-yl]-[3-[2-[1-(trifluoromethyl)cyclopropyl]pyrimidine-5-yl]azetidine-1-yl]methanone; N-[[1-[(3S)-3-(1,2,4-triazole-4-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]methyl]-3-(trifluoromethyl)benzenesulfonamide; [3-[4-(3-dimethylphosphorylphenyl)phenyl]azetidine-1-yl]-[(3S)-3-(1,2,4-triazole-4-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]-[3-[6-(trifluoromethyl)pyridazine-3-yl]oxyazetidine-1-yl]methanone; 1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-sulfonamide; tert-butyl N-[(3S)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-yl]carbamate; (3S)-1-[3-[5-(2-chloro-4-methylsulfonylphenyl)-2-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; N-[[1-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]methyl]-3-(trifluoromethyl)benzenesulfonamide; N-[[1-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]methyl]-4-(trifluoromethyl)benzenesulfonamide; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[2-[4-(trifluoromethoxy)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]methanone; [3-[5-(2,4-difluorophenyl)-4H-1,2,4-triazole-3-yl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (3S)-1-[3-[5-(4-chloro-2-methylsulfonylphenyl)-2-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[5-(2-chloro-4-methylsulfonylphenyl)pyrazine-2-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3R)-1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3R)-1-[6-[[6-(trifluoromethyl)-3-pyridyl]oxy]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[(3R)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; 2-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-N-[[1-(trifluoromethyl)cyclopropyl]methyl]-2-azaspiro[3.3]heptan-6-carboxamide; [(3S)-3-(1,2,4-triazole-4-yl)pyrroridine-1-yl]-[6-[[[1-(trifluoromethyl)cyclopropyl]amino]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[(3R)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [3-[4-(benzenesulfonyl)phenyl]azetidine-1-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]-[3-[4-[4-(trifluoromethyl)pyrimidine-2-yl]oxyphenyl]azetidine-1-yl]methanone; [3-[6-(2-chlorophenoxy)pyridazine-3-yl]azetidine-1-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; Methyl 2-methyl-2-[3-[1-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]oxyphenyl]propanoate; [2-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; Methyl 2-methyl-2-[3-[1-[(3R)-3-(tetrazole-1-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]oxyphenyl]propanoate; [(3R)-3-(tetrazole-1-yl)pyrrolidine-1-yl]-[3-[4-[4-(trifluoromethyl)pyrimidine-2-yl]oxyphenyl]azetidine-1-yl]methanone; [2-[4-fluoro-3-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [3-[(2-fluoro-4-methylsulfonylphenyl)methoxy]azetidine-1-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [2-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptan-6-yl]-[(3R)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [3-[4-(dimethylphosphorylmethyl)phenyl]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [7-[2-fluoro-4-(trifluoromethyl)phenoxy]-2-azaspiro[3.5]nonan-2-yl]-[(3S)-3-(1,2,4-triazole-4-yl)pyrrolidine-1-yl]methanone; (3S)-1-[3-[4-(2-chloro-4-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(2-chloro-4-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[(3S)-3-hydroxypyrrolidine-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[(3S)-3-hydroxypyrrolidine-1-yl]methanone; (3S)-1-[3-[4-(6-chloro-4-methylsulfonyl-3-pyridyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (3-pyrrolidine-1-ylsulfonylpyrrolidine-1-yl)-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-yl]methanone; Morpholino-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-yl]methanone; [3-[5-(4-chloro-2-fluorophenoxy)pyrazine-2-yl]azetidine-1-yl]morpholino-methanone; [3-[[rac-(1S,5R)-6,6-difluoro-3-bicyclo[3.1.0]hexanyl]methoxy]azetidine-1-yl]-[3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [6-[[2-fluoro-4-(trifluoromethyl)phenyl]methylamino]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [7-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [7-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]-[(3R)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [7-[2-fluoro-4-(trifluoromethyl)phenoxy]-2-azaspiro[3.5]nonan-2-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [7-[2-fluoro-4-(trifluoromethyl)phenoxy]-2-azaspiro[3.5]nonan-2-yl]-[(3R)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; (3S)-1-[3-[5-(4-chloro-2-fluorophenyl)pyrimidine-2-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[5-(4-chloro-2-fluorophenyl)-2-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[5-(2,4-dichlorophenyl)-2-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-(5-chloro-3-methylsulfonyl-2-pyridyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[6-(2-chloro-4-methylsulfonylphenyl)-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[6-(4-chloro-2-methylsulfonylphenyl)-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(6-chloro-4-methylsulfonyl-3-pyridyl)phenyl]azetidine-1-yl]-[(3S)-3-hydroxypyrrolidine-1-yl]methanone; (3S)-1-[3-[4-[5-(trifluoromethyl)pyrazine-2-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [(3S)-3-aminopyrrolidine-1-yl]-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]methanone; [2-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonan-7-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [2-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonan-7-yl]-[(3R)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; (3S)-1-[7-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3R)-1-[7-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[2-fluoro-4-(trifluoromethyl)phenoxy]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3R)-1-[7-[2-fluoro-4-(trifluoromethyl)phenoxy]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[2-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonane-7-carbonyl]pyrrolidine-3-carboxamide; (3R)-1-[2-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonane-7-carbonyl]pyrrolidine-3-carboxamide; [7-[2-fluoro-4-(trifluoromethyl)phenyl]sulfonyl-2,7-diazaspiro[3.5]nonan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (3S)-1-[7-[2-fluoro-4-(trifluoromethyl)phenyl]sulfonyl-2,7-diazaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; [6-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(tetrazole-1-yl)pyrroridine-1-yl]-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-fluoro-3-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [6-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3R)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [(3R)-3-(tetrazole-1-yl)pyrroridine-1-yl]-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-fluoro-3-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3R)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[7-[2-(trifluoromethyl)pyrimidine-4-yl]oxy-2-azapiro[3.5]nonan-2-yl]methanone; N-[2-[3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.5]nonane-7-yl]-3-(trifluoromethoxy)benzenesulfonamide; (3S)-1-[3-[4-(4-chloro-2-fluoro-phenyl)-3-methylsulfonyl-phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; N-[2-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptan-6-yl]-2-(trifluoromethyl)benzenesulfonamide; N-[2-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3,3]heptan-6-yl]-3-(trifluoromethyl)benzenesulfonamide; N-[2-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3,3]heptan-6-yl]-4-(trifluoromethyl)benzenesulfonamide; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[5-(trifluoromethyl)pyrazine-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; (3S)-1-[6-[[2-(trifluoromethyl)phenyl]sulfonylamino]-2-azaspiro[3,3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[3-(trifluoromethyl)phenyl]sulfonylamino]-2-azaspiro[3,3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[4-(trifluoromethyl)phenyl]sulfonylamino]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-(2,2-dimethylpropylsulfonylamino)-2-azaspiro[3,3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[5-(2-chloro-4-methylsulfonylphenyl)pyrimidine-2-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[2-(2-chloro-4-methylsulfonyl-phenyl)pyrimidine-5-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[6-(1,1-dioxo-1,4-thiadinan-4-yl)-3-pyridyl]azetidine-1-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[5-(4-chloro-2-methylsulfonylphenyl)-2-pyridyl]azetidine-1-yl]-[(3R)-3-hydroxypyrrolidine-1-yl]methanone; [3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3,3]heptan-2-yl]methanone; 1-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-sulfonamide; 1-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3,3]heptan-2-carbonyl]piperidine-3-carboxamide; [3-[5-(4-chlorophenoxy)pyrazine-2-yl]azetidine-1-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]-[6-[4-(trifluoromethyl)phenyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(tetrazole-1-yl)pyrroridine-1-yl]-[6-[2-(trifluoromethyl)pyrimidine-5-yl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[7-[6-(trifluoromethyl)pyrazine-2-yl]oxy-2-azaspiro[3.5]nonan-2-yl]methanone; [7-(4-fluoro-2-methylsulfonylphenoxy)-2-azaspiro[3.5]nonan-2-yl]-[3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1,2,4-triazole-4-yl)pyrroridine-1-yl]-[3-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-3-pyridyl]azetidine-1-yl]methanone; [3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[7-[6-(trifluoromethyl)pyridazin-3-yl]oxy-2-azapiro[3.5]nonan-2-yl]methanone; [3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[7-[5-(trifluoromethyl)pyrazine-2-yl]oxy-2-azaspiro[3.5]nonan-2-yl]methanone; [(3S)-3-(1,2,4-triazole-4-yl)pyrroridine-1-yl]-[7-[5-(trifluoromethyl)pyrazine-2-yl]oxy-2-azaspiro[3.5]nonan-2-yl]methanone; (3R)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-sulfonamide; (3S)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-sulfonamide; 3-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-4,5-dihydroisoxazole-5-carboxamide; 1-[7-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonane-2-carbonyl]piperidine-3-carboxamide; 1-[7-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-sulfonamide; [6-[(3-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [6-[(4-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (3S)-1-[6-[(3-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[(4-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[3-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-3-pyridyl]azetidine-1-yl]methanone; (3S)-1-[3-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; 4-Fluoro-N-[1-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-4-piperidyl]benzenesulfonamide; N-[1-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-4-piperidyl]-4-(trifluoromethyl)benzenesulfonamide; (3S)-1-[4-[[4-(trifluoromethyl)phenyl]sulfonylamino]piperidine-1-carbonyl]pyrrolidine-3-carboxamide; 4-Chloro-N-[[1-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-4-piperidyl]methyl]benzenesulfonamide; (3S)-1-[7-(4-fluoro-2-methylsulfonyl-phenoxy)-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[6-(trifluoromethyl)pyridazin-3-yl]oxy-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[2-(trifluoromethyl)pyrimidine-4-yl]oxy-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[[3-(trifluoromethoxy)phenyl]sulfonylamino]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; N-[2-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.5]nonane-7-yl]-3-(trifluoromethoxy)benzenesulfonamide; (5S)-3-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-4,5-dihydroisoxazole-5-carboxamide; (5R)-3-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-4,5-dihydroisoxazole-5-carboxamide; 1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]azetidine-3-sulfonamide; 1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]piperidine-4-sulfonamide; N-[[1-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-4-piperidyl]methyl]-4-(trifluoromethyl)benzenesulfonamide; (3S)-1-[4-[[[4-(trifluoromethyl)phenyl]sulfonylamino]methyl]piperidine-1-carbonyl]pyrrolidine-3-carboxamide; N-[[1-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-4-piperidyl]methyl]-4-(trifluoromethoxy)benzenesulfonamide; (3S)-1-[4-[[[4-(trifluoromethoxy)phenyl]sulfonylamino]methyl]piperidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-(6,6-difluoro-2-azaspiro[3,3]heptan-2-yl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-[3-(trifluoromethyl)cyclobutyl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-(2-azaspiro[3,4]octan-2-yl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(4-fluoro-2-methylsulfonyl-phenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[6-(3-hydroxy-3-methylazetidine-1-yl)-3-pyridyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[6-[3-hydroxy-3-(trifluoromethyl)azetidine-1-yl]-3-pyridyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[6-[3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-yl]-[rac-(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-[1-(1H-tetrazole-5-yl)cyclopropyl]phenyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-[1-(2-tert-butyltetrazol-5-yl)cyclopropyl]phenyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (3S)-1-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[(4-fluoro-2-methylsulfonyl-phenyl)methyl]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[6-[3-hydroxy-3-(trifluoromethyl)azetidine-1-yl]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; rac-(3S)-1-[3-[6-[3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-[1-(2-tert-butyltetrazol-5-yl)cyclopropyl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[1-(trifluoromethyl)cyclopropyl]amino]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[1-(trifluoromethyl)cyclopropyl]amino]-2-azaspiro[3.3]heptan-2-yl]methanone; (3S)-1-[3-[6-[(3R)-3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[6-[(3S)-3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(4-fluorophenoxy)phenyl]azetidine-1-yl]-[(3R)-3-(tetrazole-2-yl)pyrrolidine-1-yl]methanone; [(3R)-3-(tetrazole-2-yl)pyrrolidine-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-yl]methanone; [3-[6-[(3R)-3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[6-[(3S)-3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[6-(4-chloro-2-methylsulfonylphenoxy)-3-pyridyl]azetidine-1-yl]-[(3S)-3-(1,2,4-triazole-4-yl)pyrrolidine-1-yl]methanone; 1-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-sulfonamide; 1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-sulfonamide; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[3-[[4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[3-[[3-(trifluoromethylsulfonyl)phenyl]methoxy]azetidine-1-yl]methanone; Methyl 2-[4-[1-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]phenyl]benzoate; 1-[4-[1-[rac-(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]phenyl]piperidine-2-carboxamide; [3-[[2-fluoro-5-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[3-[[4-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]methanone; [(3S)-3-(tetrazole-1-yl)pyrroridine-1-yl]-[3-[2-[1-(trifluoromethyl)cyclopropyl]pyrimidine-5-yl]azetidine-1-yl]methanone; (3S)-1-[7-[[5-(trifluoromethyl)pyrazine-2-yl]amino]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3R)-1-[7-[[5-(trifluoromethyl)pyrazine-2-yl]amino]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[5-(trifluoromethyl)pyrimidine-2-yl]oxy-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(4-fluorophenoxy)phenyl]azetidine-1-yl]-[(3S)-3-(tetrazole-2-yl)pyrrolidine-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[(3S)-3-(tetrazole-2-yl)pyrrolidine-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[(3R)-3-(tetrazole-2-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]-[3-[4-[[1-(trifluoromethyl)cyclopropyl]methoxy]phenyl]azetidine-1-yl]methanone; [(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]-[3-[4-[5-(trifluoromethyl)pyrazine-2-yl]oxyphenyl]azetidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[3-[6-[[1-(trifluoromethyl)cyclopropyl]amino]-3-pyridyl]azetidine-1-yl]methanone; 4,4-difluoro-1-[4-[1-[rac-(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]phenyl]piperidine-2-carboxamide; (3S)-1-[7-[5-(trifluoromethyl)pyrazine-2-yl]oxy-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; [3-[[5-chloro-2-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[3-chloro-5-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethoxy)phenyl]methylamino]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[3-fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-chloro-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; 2-[4-[1-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]phenyl]benzoic acid; (3S)-1-[3-[4-(3,5-dimethylpyrazole-1-yl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [6-[(3-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [3-[[2-chloro-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [3-[[3-fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethoxy)phenyl]methylamino]azetidine-1-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [3-[[5-chloro-2-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [3-[[3-chloro-5-(trifluoromethyl)phenyl]methylamino]azetidine-1-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-2-pyridyl]azetidine-1-yl]methanone; (3S)-1-[3-[6-(2-azaspiro[3.4]octan-2-yl)-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; 1-[3-[6-(2-azaspiro[3,4]octan-2-yl)-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-sulfonamide; 1-[4-[1-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]phenyl]piperidine-2-carboxamide; (3S)-1-[7-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; 2-[4-[1-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]phenyl]benzamide; (3S)-1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl-methyl-amino]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[[4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[[3-(trifluoromethylsulfonyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[5-[6-(trifluoromethyl)-3-pyridyl]-1,2,4-oxadiazole-3-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[5-[3-(trifluoromethyl)-1-bicyclo[1.1.1]pentanyl]-1,2,4-oxadiazole-3-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; rac-(3S)-1-[3-[6-[3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; N-ethyl-2-[4-[1-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]phenyl]benzamide; [3-[cyclopropylmethyl-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]amino]azetidine-1-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-(3-hydroxyazetidine-1-yl)methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-(3-hydroxy-3-methylazetidine-1-yl)methanone; 1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]azetidine-3-carboxamide; 1-[3-[4-[5-(trifluoromethyl)pyrimidine-2-yl]oxyphenyl]azetidine-1-carbonyl]azetidine-3-carboxamide; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl-methyl-amino]azetidine-1-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; (3S)-1-[3-(5-spiro[3,3]heptan-2-ylpyrazine-2-yl)azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-[4-methyl-2-(pyrrolidine-1-carbonyl)phenyl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[3-(methylsulfonimidoyl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl-methyl-amino]azetidine-1-yl]-[(3S)-3-(1,2,4-triazole-4-yl)pyrrolidine-1-yl]methanone; N-[1-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-carbonyl]azetidine-3-yl]methanesulfonamide; N-[1-[3-[4-[[1-(trifluoromethyl)cyclopropyl]methoxy]phenyl]azetidine-1-carbonyl]azetidine-3-yl]methanesulfonamide; N-[1-[3-[4-[5-(trifluoromethyl)pyrazine-2-yl]oxyphenyl]azetidine-1-carbonyl]azetidine-3-yl]methanesulfonamide; N-[1-[3-[6-[3-(trifluoromethyl)azetidine-1-yl]-3-pyridyl]azetidine-1-carbonyl]azetidine-3-yl]methanesulfonamide; (3S)-1-[3-[3-[5-(2,2-dimethylpropyl)-1,3,4-oxadiazole-2-yl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[3-[5-(2,2-dimethylpropyl)-1,3,4-oxadiazole-2-yl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (3S)-1-[3-[4-[3-(2,2-dimethylpropyl)triazole-4-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; rac-(3S)-1-[3-[6-(2,2-difluoro-5-azaspiro[2,4]heptan-5-yl)-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [(3S)-3-(tetrazole-1-yl)pyrroridine-1-yl]-[6-[[6-(trifluoromethyl)pyridazin-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; tert-butyl 2-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl-methyl-amino]azetidine-1-carbonyl]-2,8-diazaspiro[3.5]nonane-8-carboxylate; N-[1-[2-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonane-7-carbonyl]azetidine-3-yl]methanesulfonamide; (3S)-1-[3-[6-(6-oxa-2-azaspiro[3.4]octan-2-yl)-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[6-(5-oxa-2-azaspiro[3,4]octan-2-yl)-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [7-[[6-(difluoromethoxy)-3-pyridyl]methyl]-2-azaspiro[3.5]nonan-2-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [6-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [6-[[4-fluoro-2-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; N-[1-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-carbonyl]azetidine-3-yl]acetamide; N-[1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]azetidine-3-yl]acetamide; N-[1-[7-[[1-(trifluoromethyl)cyclopropyl]methoxy]-2-azaspiro[3.5]nonane-2-carbonyl]azetidine-3-yl]acetamide; N-[1-[3-[4-[5-(trifluoromethyl)pyrazine-2-yl]oxyphenyl]azetidine-1-carbonyl]azetidine-3-yl]acetamide; (3S)-1-[3-[6-[(3R)-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[6-[(3S)-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-[5-(trifluoromethyl)pyrazine-2-yl]oxyphenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[5-[[1-(trifluoromethyl)cyclopropyl]methylamino]-2-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[5-[[1-(trifluoromethyl)cyclopropyl]methylamino]pyrazine-2-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[6-[3-(trifluoromethyl)azetidine-1-yl]-3-pyridyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[2-[3-(trifluoromethyl)azetidine-1-yl]pyrimidine-5-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[(5-chloro-2-pyridyl)methyl]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[[5-(trifluoromethyl)pyrazine-2-yl]methyl]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[[6-(difluoromethoxy)-3-pyridyl]methyl]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[6-(trifluoromethyl)pyridazin-3-yl]methyl]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[2-(trifluoromethyl)pyrimidine-5-yl]methyl]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[(6S)-6-[5-(trifluoromethyl)pyrazine-2-yl]oxy-2-azaspiro[3.4]octan-2-carbonyl]pyrrolidine-3-carboxamide; [6-(4-fluorophenyl)-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(tetrazole-1-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(tetrazole-1-yl)pyrroridine-1-yl]-[6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone; (3S)-1-[3-[4-(5-cyclobutyl-4H-1,2,4-triazole-3-yl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-(3-cyclopropyl-1,2,4-triazole-1-yl)-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(triazole-1-yl)pyrrolidine-1-yl]methanone; [3-[6-(2-chlorophenoxy)-3-pyridyl]azetidine-1-yl]-[(3R)-3-(triazole-1-yl)pyrrolidine-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[(3R)-3-(triazole-1-yl)pyrrolidine-1-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3R)-3-(triazole-1-yl)pyrrolidine-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[(3R)-3-(triazole-2-yl)pyrrolidine-1-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3R)-3-(triazole-2-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl-methyl-amino]azetidine-1-yl]-[(3R)-3-(triazole-2-yl)pyrrolidine-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[(3S)-3-(triazole-1-yl)pyrrolidine-1-yl]methanone; [7-[[6-(difluoromethoxy)-3-pyridyl]methyl]-2-azaspiro[3.5]nonan-2-yl]-[(3R)-3-(triazole-1-yl)pyrrolidine-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[(3S)-3-(triazole-2-yl)pyrrolidine-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[6-(triazole-2-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[6-(triazole-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone; (3S)-1-[3-[4-(3-cyclopropyl-5-methyl-pyrazole-1-yl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-(4-chloro-2-methylsulfonylphenyl)-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (3S)-1-[3-[4-(5-cyclopropyl-4H-1,2,4-triazole-3-yl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-[5-[1-(trifluoromethyl)cyclopropyl]-4H-1,2,4-triazole-3-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[5-(trifluoromethyl)pyrimidine-2-yl]methyl]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[5-(trifluoromethyl)pyrimidine-2-yl]methyl]-2-azapiro[3.3]heptan-2-yl]methanone; (3S)-1-[6-[[5-(trifluoromethoxy)-2-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[5-(trifluoromethoxy)-2-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; rac-(3S)-1-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.4]octane-2-carbonyl]pyrrolidine-3-carboxamide; [rac-(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[6-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; (3S)-1-[7-(4-chloro-2-fluorophenyl)-2,7-diazaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-(5-chloro-3-fluoro-2-pyridyl)-2,7-diazaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; 1-[4-[1-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]phenyl]-4-(trifluoromethyl)pyridine-2-one; [3-[4-(3-cyclopropyl-5-methylpyrazole-1-yl)phenyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[3-[6-[(3R)-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[3-[6-[(3S)-3-(trifluoromethyl)pyrrolidine-1-yl]-3-pyridyl]azetidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[3-[6-[3-(trifluoromethyl)azetidine-1-yl]-3-pyridyl]azetidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[3-[2-[3-(trifluoromethyl)azetidine-1-yl]pyrimidine-5-yl]azetidine-1-yl]methanone; [3-[4-(2-chloro-4-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[5-(4-chloro-2-methylsulfonylphenyl)-2-pyridyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [7-[(5-fluoro-2-pyridyl)methyl]-2-azaspiro[3.5]nonan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[3-[5-[[1-(trifluoromethyl)cyclopropyl]methylamino]pyrazine-2-yl]azetidine-1-yl]methanone; [7-[(5-chloro-2-pyridyl)methyl]-2-azaspiro[3.5]nonan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[7-[[5-(trifluoromethyl)pyrazine-2-yl]methyl]-2-azaspiro[3.5]nonan-2-yl]methanone; [7-[[6-(difluoromethoxy)-3-pyridyl]methyl]-2-azaspiro[3.5]nonan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[7-[[1-(trifluoromethyl)cyclopropyl]methoxy]-2-azaspiro[3.5]nonane-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[7-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[7-[[3-(trifluoromethylsulfonyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonan-2-yl]methanone; [6-[[3-fluoro-5-(trifluoromethyl)-2-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[6-(trifluoromethyl)pyridazin-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[2-(trifluoromethyl)pyrimidine-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[4-fluoro-2-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [6-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [6-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[(6S)-6-[[5-(trifluoromethyl)pyrazine-2-yl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[(6R)-6-[[5-(trifluoromethyl)pyrazine-2-yl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [6-[(4-methylsulfonylphenyl)methyl]-2-azaspiro[3.4]octan-2-yl]-[rac-(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[(6S)-6-[5-(trifluoromethyl)pyrazine-2-yl]oxy-2-azaspiro[3.4]octan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[3-[1-[[4-(trifluoromethyl)phenyl]methyl]azetidine-3-yl]azetidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[5-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[4-(trifluoromethyl)-2-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[7-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2,7-diazaspiro[3.4]octan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[3-[3-[[1-(trifluoromethyl)cyclopropyl]methylamino]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[3-[3-[[[1-(trifluoromethyl)cyclopropyl]amino]methyl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; [3-[3-(5-cyclopropyl-1,3,4-oxadiazole-2-yl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[3-[3-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazole-2-yl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; (4S)-1-[4-[1-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]phenyl]-4-(trifluoromethyl)piperidine-2-one; (4R)-1-[4-[1-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]phenyl]-4-(trifluoromethyl)piperidine-2-one; [3-[4-[3-(difluoromethyl)-5-methylpyrazole-1-yl]phenyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-[5-methyl-3-(trifluoromethyl)pyrazole-1-yl]phenyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-(3-tert-butyl-5-methylpyrazole-1-yl)phenyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (3S)-1-[6-[[3-fluoro-5-(trifluoromethyl)-2-pyridyl]methyl]-2-azaspiro[3,3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2,7-diazaspiro[3.4]octane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[3-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazole-2-yl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [6-[[4-methylsulfonyl-3-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [6-[[2-methylsulfonyl-4-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [6-[[3-methylsulfonyl-4-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [rac-(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[3-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [rac-(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[4-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[4-(trifluoromethyl)pyrazole-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[3-[4-[5-[1-(trifluoromethyl)cyclopropyl]-4H-1,2,4-triazole-3-yl]phenyl]azetidine-1-yl]methanone; (3S)-1-[3-[3-[[1-(trifluoromethyl)cyclopropyl]methylamino]-1-bicyclo[1.1.1]pentanyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[3-[[[1-(trifluoromethyl)cyclopropyl]amino]methyl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; rac-(1S,4R,5R)-2-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-2-azabicyclo[2.1.1]hexane-5-carboxamide; (3S)-1-[3-[3-(5-cyclopropyl-1,3,4-oxadiazole-2-yl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-(4-chloro-2-methylsulfonylphenyl)-2,7-diazaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; [6-[(5-methylsulfonyl-2-pyridyl)methyl]-2-azapiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-[3-(2,2-dimethylpropyl)triazole-4-yl]phenyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[3-(trifluoromethyl)-1,2,4-triazole-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[4-(trifluoromethyl)oxazole-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[3-(trifluoromethyl)-1,2,4-thiadiazole-5-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[3-[3-[5-(trifluoromethyl)pyrazine-2-yl]oxy-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[4-(trifluoromethyl)imidazole-1-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [3-[4-(3,5-diisopropylpyrazole-1-yl)phenyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-(3,5-dimethyl-1,2,4-triazole-1-yl)phenyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[7-[[5-(trifluoromethyl)-2-pyridyl]amino]-2-azaspiro[3.5]nonan-2-yl]methanone; [6-[(3-fluoro-5-methylsulfonyl-phenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [6-[[4-methylsulfonyl-3-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.4]octan-2-yl]-[rac-(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidine-1-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[7-[[6-(trifluoromethyl)-3-pyridyl]methyl]-2-azaspiro[3.5]nonan-2-yl]methanone; [3-[6-(2-chlorophenoxy)-3-pyridyl]azetidine-1-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [6-[(3,5-difluoro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [7-[methyl-[5-(trifluoromethyl)pyrazine-2-yl]amino]-2-azaspiro[3.5]nonan-2-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [6-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]-[3-[[4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidine-1-yl]methanone; [6-(4-methylsulfonylphenyl)-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[6-[4-(trifluoromethylsulfonyl)phenyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[3-[4-[2-(trifluoromethyl)pyrimidine-5-yl]oxyphenyl]azetidine-1-yl]methanone; [(3S)-3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[7-[[5-(trifluoromethyl)pyrazine-2-yl]amino]-2-azaspiro[3.5]nonan-2-yl]methanone; [7-(5-chloro-2-methylsulfonylphenoxy)-2-azaspiro[3.5]nonan-2-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [3-[4-(3,5-dimethylpyrazole-1-yl)phenyl]azetidine-1-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [3-[6-(N-methylanilino)-3-pyridyl]azetidine-1-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; 2-Methoxy-4-[[2-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]benzonitrile; [3-[4-[1-methyl-3-(trifluoromethyl)pyrazole-4-yl]phenyl]azetidine-1-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [3-[6-(4-fluorophenoxy)-3-pyridyl]azetidine-1-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [3-(4-cyclopropyl-2-fluorophenoxy)azetidine-1-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [3-(4-chloro-3-cyclopropyl-phenoxy)azetidine-1-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [3-[4-[5-[(1-methylcyclopropyl)methyl]-4H-1,2,4-triazole-3-yl]phenyl]azetidine-1-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[4-(trifluoromethyl)thiazole-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; (3S)-1-[6-[[4-(trifluoromethyl)pyrazole-1-yl]methyl]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[4-(trifluoromethyl)imidazole-1-yl]methyl]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[3-(trifluoromethyl)-1,2,4-triazole-1-yl]methyl]-2-azaspiro[3,3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[4-(trifluoromethyl)oxazole-2-yl]methyl]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[3-(trifluoromethyl)-1,2,4-thiadiazole-5-yl]methyl]-2-azaspiro[3,3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[4-(trifluoromethyl)thiazole-2-yl]methyl]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; [6-[(5-fluoro-3-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [6-[(2-fluoro-4-methylsulfonyl-phenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [6-([1,2,4]triazolo[1,5-a]pyridine-7-ylmethyl)-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-yl]methanone; (3S)-1-[6-([1,2,4]triazolo[1,5-a]pyridine-6-ylmethyl)-2-azaspiro[3,3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; [6-(1H-pyrazolo[4,3-b]pyridine-5-ylmethyl)-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[1-(trifluoromethyl)pyrazole-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; 3-[[2-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3,3]heptan-6-yl]methyl]-5-(trifluoromethyl)benzonitrile; 4-[[2-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3,3]heptan-6-yl]methyl]-2-(trifluoromethyl)benzonitrile; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[6-(trifluoromethoxy)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[3-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(4-cyclopropylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[3-[3-[[6-(trifluoromethyl)-3-pyridyl]methyl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; [6-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[3-(1H-1,2,4-triazole-5-yl)azetidine-1-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[3-(1H-1,2,4-triazole-5-yl)azetidine-1-yl]methanone; [6-[[4-fluoro-2-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[3-(1H-1,2,4-triazole-5-yl)azetidine-1-yl]methanone; [6-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[3-(1H-1,2,4-triazole-5-yl)azetidine-1-yl]methanone; [6-[(3-chloro-5-fluoro-2-pyridyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[3-(1H-1,2,4-triazole-5-yl)azetidine-1-yl]methanone; [3-(1H-1,2,4-triazole-5-yl)azetidine-1-yl]-[6-[[5-(trifluoromethoxy)-2-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-fluoro-5-(trifluoromethyl)-2-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[3-(1H-1,2,4-triazole-5-yl)azetidine-1-yl]methanone; [3-(1H-1,2,4-triazole-5-yl)azetidine-1-yl]-[7-[[5-(trifluoromethyl)-2-pyridyl]methyl]-2,7-diazaspiro[3.4]octan-2-yl]methanone; [7-[(5-chloro-2-pyridyl)methyl]-2-azaspiro[3.5]nonan-2-yl]-[3-(1H-1,2,4-triazole-5-yl)azetidine-1-yl]methanone; [7-[[6-(difluoromethoxy)-3-pyridyl]methyl]-2-azaspiro[3.5]nonan-2-yl]-[3-(1H-1,2,4-triazole-5-yl)azetidine-1-yl]methanone; [3-(1H-1,2,4-triazole-5-yl)azetidine-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-yl]methanone; [3-(1H-1,2,4-triazole-5-yl)azetidine-1-yl]-[3-[4-[3-(trifluoromethyl)azetidine-1-yl]phenyl]azetidine-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[3-(1H-1,2,4-triazole-5-yl)azetidine-1-yl]methanone; [3-[4-[5-[(1-methylcyclopropyl)methyl]-4H-1,2,4-triazole-3-yl]phenyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[3-(5-cyclopropyl-1H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; (3S)-1-[3-[4-[5-methyl-3-(trifluoromethyl)pyrazole-1-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [4-[(2-chloro-4-methylsulfonylphenyl)methoxy]-1-piperidyl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (3S)-1-[4-[(2-chloro-4-methylsulfonyl-phenyl)methoxy]piperidine-1-carbonyl]pyrrolidine-3-carboxamide; [4-[[4-methylsulfonyl-3-(trifluoromethyl)phenoxy]methyl]-1-piperidyl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (3S)-1-[4-[[4-methylsulfonyl-3-(trifluoromethyl)phenoxy]methyl]piperidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[3-(5-cyclopropyl-3-methylpyrazole-1-yl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[3-(3,5-dimethylpyrazole-1-yl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [4-[[2-fluoro-4-(trifluoromethoxy)phenyl]methoxy]-1-piperidyl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [4-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]-1-piperidyl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (3S)-1-[4-[[2-fluoro-4-(trifluoromethoxy)phenyl]methoxy]piperidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[4-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]piperidine-1-carbonyl]pyrrolidine-3-carboxamide; Methyl 5-[[2-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3,3]heptan-6-yl]methyl]-2-(trifluoromethoxy)benzoate; [4-[[2-methylsulfonyl-4-(trifluoromethyl)phenoxy]methyl]-1-piperidyl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-yl]-[4-(5-cyclopropyl-1H-1,2,4-triazole-3-yl)piperazine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[5-(trifluoromethylsulfonyl)-2-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [4-(5-chlorooxazolo[4,5-b]pyridine-2-yl)piperazine-1-yl]-[3-[[2-fluoro-4-(trifluoromethoxy)phenyl]methoxy]azetidine-1-yl]methanone; 4-[[2-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3,3]heptan-6-yl]methyl]benzenesulfonamide; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[5-[3-(trifluoromethyl)azetidine-1-yl]pyrazine-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[6-[[5-[[1-(trifluoromethyl)cyclopropyl]methylamino]pyrazine-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[6-[[4-[3-(trifluoromethyl)azetidine-1-yl]sulfonylphenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[(6S)-6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[(6R)-6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[(6S)-6-[[3-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[(6R)-6-[[3-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone; [6-[[1-methyl-3-(trifluoromethyl)pyrazole-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [6-[[2-methyl-5-(trifluoromethyl)pyrazole-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [6-[[1-methyl-5-(trifluoromethyl)pyrazole-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [6-[[2-methyl-4-(trifluoromethyl)pyrazole-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[1-(2,2,2-trifluoroethyl)pyrazole-4-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; 4-[[2-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3,3]heptan-6-yl]methyl]-2-(trifluoromethoxy)benzamide; [(3S)-3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-2-pyridyl]azetidine-1-yl]methanone; [(3S)-3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[3-[[6-(trifluoromethyl)-3-pyridyl]methoxymethyl]azetidine-1-yl]methanone; [3-[4-(1-methylsulfonylcyclopropyl)phenyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [4-[(3-chloro-5-methylsulfonyl-phenoxy)methyl]-1-piperidyl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; 5-[[2-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3,3]heptan-6-yl]methyl]-2-(trifluoromethoxy)benzamide; [rac-(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[3-[4-(trifluoromethylsulfonimidoyl)phenyl]azetidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[3-[3-[[5-(trifluoromethyl)pyrazine-2-yl]amino]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; Methyl 4-[[2-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3,3]heptan-6-yl]methyl]-2-(trifluoromethoxy)benzoate; [4-[[2-methylsulfonyl-4-(trifluoromethoxy)phenoxy]methyl]-1-piperidyl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[4-[[6-(trifluoromethyl)-3-pyridyl]methoxymethyl]-1-piperidyl]methanone; [(3S)-3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[4-[[6-(trifluoromethyl)-3-pyridyl]oxymethyl]-1-piperidyl]methanone; [(3S)-3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[4-[[6-(trifluoromethyl)-3-pyridyl]methoxy]-1-piperidyl]methanone; [4-[[4-fluoro-3-(trifluoromethyl)phenoxy]methyl]-1-piperidyl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [4-[[3-fluoro-5-(trifluoromethyl)phenoxy]methyl]-1-piperidyl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [3-(3-isobutyl-1H-pyrazole-5-yl)pyrrolidine-1-yl]-[6-[[5-(trifluoromethyl)pyrazine-2-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[6-[[5-(trifluoromethylsulfonyl)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-fluoro-5-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3,3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; N'-[2-[3-[1-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]-1-bicyclo[1.1.1]pentanyl]acetyl]cyclopropanecarbozide; [4-[[2-methylsulfonyl-4-(trifluoromethoxy)phenyl]methoxy]-1-piperidyl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (3S)-1-[4-[[2-methylsulfonyl-4-(trifluoromethoxy)phenyl]methoxy]piperidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[3-(4-chloro-2-methylsulfonylphenyl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; 2-Methoxy-4-[[1-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-4-piperidyl]oxymethyl]benzonitrile; (3S)-1-[2-(4-chloro-2-methylsulfonylphenyl)-6-azaspiro[3,4]octane-6-carbonyl]pyrrolidine-3-carboxamide; 2-Methoxy-4-[[1-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-4-piperidyl]oxymethyl]benzamide; (3S)-1-[3-[3-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[2-[(4-chloro-2-methylsulfonyl-phenyl)methyl]-6-azaspiro[3.4]octane-6-carbonyl]pyrrolidine-3-carboxamide; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[3-(trifluoromethoxy)phenyl]sulfonyl-2-azapiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[7-[3-(trifluoromethyl)phenyl]sulfonyl-2-azapiro[3.5]nonan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[7-[4-(trifluoromethyl)phenyl]sulfonyl-2-azapiro[3.5]nonan-2-yl]methanone; [3-[3-(4-fluorophenyl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[3-(4-methylsulfonylphenyl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[4-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[3-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-(methylsulfonimidoyl)-5-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[rac-(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethylsulfonimidoyl)phenyl]methoxy]azetidine-1-yl]-[rac-(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[4-[[5-(trifluoromethyl)pyrazine-2-yl]amino]cuban-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [rac-(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[6-[[3-(trifluoromethoxy)phenyl]sulfonimidoyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-fluoro-5-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[rac-(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [rac-(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[7-[[4-(trifluoromethyl)phenyl]sulfonimidoyl]-2-azaspiro[3.5]nonan-2-yl]methanone; [rac-(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[7-[[3-(trifluoromethyl)phenyl]sulfonimidoyl]-2-azaspiro[3.5]nonan-2-yl]methanone; [3-[4-[2-(methylsulfonimidoyl)phenyl]phenyl]azetidine-1-yl]-[rac-(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[(8R)-8-methyl-8-oxo-8-lambda6-thia-9-azatricyclo[8.4.0.02,7]tetradeca-1(10),2(7),3,5,8,11,13-heptaen-12-yl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[(8S)-8-methyl-8-oxo-8-lambda6-thia-9-azatricyclo[8.4.0.02,7]tetradeca-1(10),2(7),3,5,8,11,13-heptaen-12-yl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[3-(4-fluoro-2-methylsulfonylphenyl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[3-[3-[3-(trifluoromethoxy)phenyl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; [(3S)-3-(4H-1,2,4-triazole-3-yl)pyrroridine-1-yl]-[4-[[5-(trifluoromethyl)-2-pyridyl]methyl]piperazine-1-yl]methanone; [4-[(2-methyloxazole-4-yl)methyl]piperazine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [4-[(4-methylthiazole-5-yl)methyl]piperazine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [4-[(5-chloro-1,3-dimethylpyrazole-4-yl)methyl]piperazine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; 4-[[2-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3,3]heptan-6-yl]oxy]-2-(trifluoromethyl)benzonitrile; 5-Fluoro-2-[3-[1-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]azetidine-3-yl]-1-bicyclo[1.1.1]pentanyl]benzonitrile; [3-[3-(3-methyl-1H-pyrazole-5-yl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [6-[[1-methyl-4-(trifluoromethyl)pyrazole-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[3-[3-[4-(trifluoromethylsulfonyl)phenyl]-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]methanone; [3-[3-(4-chloro-2-methylsulfonylphenyl)-1-bicyclo[1.1.1]pentanyl]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [6-[(5-chloro-1,3-dimethylpyrazole-4-yl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; 5-[[2-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3,3]heptan-6-yl]oxy]-2-(trifluoromethyl)benzonitrile; [6-[(5-fluoro-2-pyridyl)oxy]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [6-[1-methyl-3-(trifluoromethyl)pyrazole-4-yl]oxy-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazole-5-yl)pyrroridine-1-yl]-[3-[[5-(trifluoromethyl)pyrazine-2-yl]amino]-1-bicyclo[1.1.1]pentanyl]methanone; (3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]-[6-[4-(trifluoromethylsulfonimidoyl)phenoxy]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-triazole-5-yl)pyrroridine-1-yl]-[6-[[3-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-triazole-5-yl)pyrroridine-1-yl]-[6-[[3-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-triazole-5-yl)pyrroridine-1-yl]-[6-[[3-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; 5-[[2-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptan-6-yl]methyl]-2-(trifluoromethyl)benzonitrile; (3S)-1-[6-[[1-methyl-5-(trifluoromethyl)pyrazole-3-yl]methyl]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[1-methyl-5-(trifluoromethyl)pyrazole-4-yl]methyl]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[3-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3,3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[4-cyano-3-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3,3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[6-(trifluoromethoxy)-3-pyridyl]methyl]-2-azaspiro[3.3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; 5-[[2-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3,3]heptan-6-yl]methyl]-2-(trifluoromethyl)benzonitrile; [(3S)-3-(1H-triazole-5-yl)pyrroridine-1-yl]-[6-[[4-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [(3S)-3-(1H-triazole-5-yl)pyrroridine-1-yl]-[6-[[4-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; rac-(3S)-1-[6-[[2-fluoro-4-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3,3]heptan-2-carbonyl]pyrrolidine-3-carboxamide; [6-[[2-fluoro-4-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[rac-(3S)-3-(1H-triazole-4-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-triazole-4-yl)pyrroridine-1-yl]-[6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-fluoro-5-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-triazole-4-yl)pyrrolidine-1-yl]methanone; [(3S)-3-(1H-triazole-4-yl)pyrroridine-1-yl]-[6-[[5-(trifluoromethyl)-1H-pyrazole-3-yl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; and [6-[[2-fluoro-4-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3,3]heptan-2-yl]-[rac-(3S)-3-(1H-1,2,4-triazole-3-yl)pyrrolidine-1-yl]methanone A compound according to claim 1, or a pharmaceutically acceptable salt thereof, selected from the above.

13. A compound of formula (I) [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[(3S)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; 1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; (+)- or (-)-[2-(2-chloro-4-fluorophenoxy)-7-azaspiro[3.5]nonan-7-yl]-[(3R)-3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-imidazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[(3S)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[(3R)-3-(1H-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[3-chloro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; [3-[[2-chloro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (-)- or (+)-[3-[[2,4-bis(trifluoromethyl)phenyl]methoxy]azetidine-1-yl]-[3-(1H-1,2,4-triazole-5-yl)pyrrolidine-1-yl]methanone; (+)- or (-)-1-[3-[4-(2,4-difluorophenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (+)- or (-)-[3-(1H-triazole-5-yl)pyrrolidine-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-yl]methanone; (-)- or (+)-[3-(1H-triazole-5-yl)pyrrolidine-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-yl]methanone; and 4-[1-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-yl]oxazolidine-2-one A compound according to claim 12, or a pharmaceutically acceptable salt thereof, selected from the above.

14. A method for producing the compound described in any one of claims 1 to 13, (a) Formula 2 【Chemistry 44】 The amine of (wherein p, q and R 4 are as defined in any one of claims 1 to 11) is carboxylic acid 3a 【Chemistry 45】 (wherein L, A, B, and R1 to R3 are as defined in any one of claims 1 to 11) and CDI, DCC, HATU, HBTU, HOBT, TBTU, T ３ The reaction is carried out in the presence of a coupling reagent selected from P and Mukaiyama reagents, and optionally in the presence of a base selected from TEA, DIPEA (Huenig base), and DMAP, to form formula (IB). 【Chemistry 46】 To form a compound of (wherein A, B, L, p, q, and R1 to R4 as defined in any one of claims 1 to 11); or (b) Formula 2 【Chemistry 47】 The amine (wherein p, q and R 4 are as defined in any one of claims 1 to 11) is used as carboxylic acid chloride 3b 【Chemistry 48】 (wherein L, A, B, and R1 to R3 are as defined in any one of claims 1 to 11) are reacted in the presence of a base selected from TEA, Huenig base, pyridine, DMAP, and lithium bis(trimethylsilyl)amide to obtain a compound of formula (IB) (wherein A, B, L, p, q, and R1 to R3 are as defined in any one of claims 1 to 11). １ ~R ４ (as defined in any one of claims 1 to 13); or (c) Formula 1 【Chemistry 49】 A first amine of formula 2 (wherein A, B, L, and R1 to R3 are as defined in any one of claims 1 to 11) [Transformation 50] A second amine of formula (wherein X, Y, and Z are as defined in any one of claims 1 to 11) is reacted with sodium bicarbonate and a urea-forming reagent selected from bis(trichloromethyl) carbonate, phosgene, trichloromethyl chloroformate, (4-nitrophenyl) carbonate, and 1,1'-carbonyldiimidazole to form formula (IA). 【Chemistry 51】 To form a compound of the form (wherein A, B, L, p, q, and R1 to R4 are as defined in any one of claims 1 to 11), Methods that include...

15. A compound according to any one of claims 1 to 13 or a pharmaceutically acceptable salt thereof, for use as a therapeutically active substance.

16. A compound according to any one of claims 1 to 13 or a pharmaceutically acceptable salt thereof for treating or preventing neuroinflammation, neurodegenerative diseases, pain, cancer, mental disorders, and / or inflammatory bowel disease.

17. A compound according to any one of claims 1 to 13 or a pharmaceutically acceptable salt thereof for treating or preventing multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, anxiety, migraine, depression, hepatocellular carcinoma, colon carcinogenesis, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, pain-related spasticity, abdominal pain, abdominal pain associated with irritable bowel syndrome, and / or visceral pain.

18. A pharmaceutical composition comprising a compound according to any one of claims 1 to 13 or a pharmaceutically acceptable salt thereof.

19. The pharmaceutical composition according to claim 18 for treating or preventing neuroinflammation, neurodegenerative diseases, pain, cancer, mental disorders, and / or inflammatory bowel disease.

20. The pharmaceutical composition according to claim 18 for treating or preventing multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, anxiety, migraine, depression, hepatocellular carcinoma, colon carcinogenesis, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, pain-related spasticity, abdominal pain, abdominal pain associated with irritable bowel syndrome, and / or visceral pain.

21. Use of a compound according to any one of claims 1 to 13 or a pharmaceutically acceptable salt thereof for preparing a medicament for the treatment or prevention of neuroinflammation, neurodegenerative diseases, pain, cancer, mental disorders, and / or inflammatory bowel disease.

22. Use of a compound according to any one of claims 1 to 13 or a pharmaceutically acceptable salt thereof for preparing a medicament for the treatment or prevention of multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, anxiety, migraine, depression, hepatocellular carcinoma, colon carcinogenesis, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, pain-related spasticity, abdominal pain, abdominal pain associated with irritable bowel syndrome, and / or visceral pain.

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