Novel heterocyclic carbonyl cyclic compounds as MAGL inhibitors

Abstract

The present invention provides compounds of Formula (I) CB (I) or a pharmaceutically acceptable salt thereof, wherein R3 to R5, R4a, B and C are as described herein; comprising the compound; methods of making the compounds; and methods of using the compounds. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to organic compounds useful for treating or preventing mammals, and in particular to monoacylglycerol lipase (MAGL) inhibitors useful for treating or preventing 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 Art

[0002] Endocannabinoids (EC) are lipid signals that exert their biological effects by interacting with cannabinoid receptors (CBR), CB1 and CB2. They regulate a variety of physiological processes, including neuroinflammation, neurodegenerative diseases 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 can hydrolyze 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 microglia (Chanda, PK et al., Molecular pharmacology 2010, 78, 996; Viader, A. et al., Cell reports 2015, 12, 798.). 2-AG is hydrolyzed to form arachidonic acid (AA), a precursor of prostaglandins (PG) and leukotrienes (LT). AA oxidation metabolism is increased in inflamed tissues. The inflammatory process involves two major enzyme reaction pathways for arachidonic acid oxidation, namely cyclooxygenases that produce PG and 5-lipoxygenases that produce LT. Among the various cyclooxygenase products formed during the inflammatory process, PGE2 is one of the most important products. These products have been detected at sites of inflammation (e.g., in the cerebrospinal fluid of patients with neurodegenerative diseases) and are believed to contribute to inflammatory responses and disease progression. The 2-AG hydrolase activity in the nervous system of mice lacking MAGL (Mgll- / -) was significantly reduced, while the levels of 2-AG were increased, while other arachidonic acid-containing phospholipids and neutral lipids (including anandamide (AEA) and other free fatty acids) remained unchanged. In contrast, the levels of AA-derived and AA-derived prostaglandins and other eicosanoids (including prostaglandin E2 (PGE2), D2 (PGD2), F2 (PGF2), and thromboxane B2 (TXB2)) were greatly reduced. Phospholipase A 2 (PLA 2 ) has been considered as the main source of AA, but cPLA 2 The AA levels in the brains of deficient mice remained unchanged, thus reinforcing the key role of MAGL in the brain in regulating AA production and brain inflammatory processes.

[0003] Neuroinflammation is a common pathological change characteristic of brain diseases, including but not limited to neurodegenerative diseases (e.g., multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy and mental disorders such as anxiety and migraine). In the brain, the production of eicosanoids and prostaglandins controls the neuroinflammatory process. The proinflammatory agent lipopolysaccharide (LPS) causes a stable time-dependent increase in brain eicosanoid production, which is significantly reduced in Mgll- / - mice. LPS treatment also causes a general increase in proinflammatory cytokines (including interleukin-1-a (IL-1-a), IL-1b, IL-6) and tumor necrosis factor-a (TNF-a) (suppressed in Mgll- / - mice).

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

[0005] In addition, in animal models of various neurodegenerative diseases (including but not limited to Alzheimer's disease, Parkinson's disease and multiple sclerosis), it has been demonstrated that genetic and / or pharmacological disruption of MAGL activity has a protective effect. For example, irreversible MAGL inhibitors have been widely used in preclinical models of neuroinflammation and neurodegenerative diseases (Long, JZ et al., Nature chemical biology 2009, 5, 37.). Systemic injection of such inhibitors can reproduce the phenotype of Mgll- / - mice in the brain, including increased 2-AG levels, decreased AA levels and related eicosanoid production, and prevent cytokine production and microglial activation after LPS-induced neuroinflammation (Nomura, DK et al., Science 2011, 334, 809.), fully confirming that MAGL is a drug target.

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

[0007] In addition, oligodendrocytes (OL), myelinating cells of the central nervous system and their precursors (OPC) express cannabinoid receptor 2 (CB2) on their membranes. 2-AG is an endogenous ligand for CB1 and CB2 receptors. It is reported that the pharmacological inhibition of cannabinoids and MAGL weakens the excitotoxicity of OL and OPC, and therefore may have a neuroprotective effect (Bernal-Chico, A. et al., Glia 2015, 63, 163.). In addition, the pharmacological inhibition of MAGL increases the number of myelinating OLs in the mouse brain, indicating that MAGL inhibition can promote the differentiation of OPCs in myelinating OLs in vivo (Alpar, A. et al., Nature communications 2014, 5, 4421.). In a mouse model of progressive multiple sclerosis, the inhibition of MAGL can also promote myelin regeneration and functional recovery (Feliu A. et al., Journal of Neuroscience 2017, 37 (35), 8385.).

[0008] In addition, in recent years, metabolism, especially lipid metabolism, has received great attention in cancer research. Researchers believe that de novo fatty acid synthesis plays an important role in tumor development. Many studies have shown that endocannabinoids have anti-tumor effects, including anti-proliferation, induction of apoptosis, and anti-metastasis. MAGL, as an important degrading enzyme in lipid metabolism and endocannabinoid systems, and as a component of gene expression characteristics, affects different aspects of tumor occurrence (including glioblastoma) (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 physiological and pathological effects (Marquez L. et al., PLoS One 2009, 4, e6893). All these effects are mainly driven by cannabinoid receptors (CBR), CB1 and CB2. CB1 receptors are present in the entire GI tract of animals and healthy humans, especially in the enteric nervous system (ENS) and epithelial lining and smooth muscle cells of blood vessels in the colon wall (Wright K. et al., Gastroenterology 2005, 129, 437; Duncan, M. et al., Aliment. Pharmacol. Ther. 2005, 22, 667). CB1 activation produces antiemetic, antiperistaltic 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) in the GI tract propria (Wright K. et al., Gastroenterology 2005, 129, 437), and mainly act on the human colonic tissue epithelium associated with inflammatory bowel disease (IBD). Activation of CB2 exerts anti-inflammatory effects by reducing proinflammatory cytokines. MAGL expression in colonic tissue of UC patients increases (Marquez L. et al., PLoS One 2009, 4, e6893), and 2-AG levels in plasma of IBD patients increase (Grill, M. et al., Sci. Rep. 2019, 9, 2358). Several animal studies have confirmed the potential of MAGL inhibitors for symptomatic treatment of IBD. MAGL inhibition prevents TNBS-induced colitis in mice via CB1 / CB2 MoA and reduces local circulating inflammatory markers (Marquez L. et al., PLoS One 2009, 4, e6893). In addition, MAGL inhibits MoA driven by CB1 to improve intestinal wall integrity and intestinal permeability (Wang, J. et al., Biochem. Biophys. Res. Commun. 2020, 525, 962).

[0010] In summary, inhibition of 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. In addition, inhibition of the action and / or activation of MAGL is a promising new therapeutic strategy for providing neuroprotection and remyelination. Therefore, there is an urgent unmet medical need for new MAGL inhibitors. Summary of the invention

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

[0012]

[0013] or a pharmaceutically acceptable salt thereof, wherein R 3 To R 5 , R 4a , B and C are as described herein.

[0014] In one aspect, the present invention provides a method of making a compound of formula (IA) or (IB) as described herein, the method comprising:

[0015] (a) an amine of formula 2, wherein p, q and R 4 As stated in this article,

[0016]

[0017] with carboxylic acid 3a, where L, A, B and R 1 To R 3 As described in this article

[0018]

[0019] In coupling reagents such as CDI, DCC, HATU, HBTU, HOBT, TBTU, T 3 P or the presence of a reagent, and optionally in the presence of a base such as TEA, DIPEA (Huenig's base) or DMAP, to form the compound of formula (IB), wherein A, B, L, p, q and R 1 To R 4 As defined in this article

[0020] or

[0021] (b) an amine of formula 2, wherein p, q and R 4 As stated in this article,

[0022]

[0023] With carboxylic acid chloride 3b, where L, A, B and R 1 To R 3 As described in this article

[0024]

[0025] In the presence of a base such as TEA, Huenig's base, pyridine, DMAP or lithium bis(trimethylsilyl)amide, to form the compound of formula (IB), wherein A, B, L, p, q and R 1 To R 4 as defined herein; or

[0026] (c) making a first amine of formula 1, wherein A, B, L and R 1 To R 3 As stated in this article,

[0027]

[0028] and a second amine 2, wherein X, Y and Z are as described herein,

[0029]

[0030] In the presence of a base such as sodium bicarbonate and a urea-forming agent such as bis(trichloromethyl) carbonate, phosgene, trichloromethyl chloroformate, (4-nitrophenyl) carbonate or 1,1'-carbonyldiimidazole, to form the compound of formula (IA), wherein A, B, L, p, q and R 1 To R 4 As this article

[0031] Defined

[0032]

[0033] In another aspect, the present invention provides a compound of formula (I) as described herein, manufactured according to a method described herein.

[0034] In another aspect, the present invention provides a compound of formula (I) as described herein for use as a therapeutically active substance.

[0035] In another aspect, the present invention provides a pharmaceutical composition comprising a compound of formula (I) as described herein and a therapeutically inert carrier.

[0036] In another 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.

[0037] In another aspect, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, or a pharmaceutical composition as described herein for treating or preventing neuroinflammation, neurodegenerative diseases, pain, cancer, mental disorders and / or inflammatory bowel disease in mammals.

[0038] In another aspect, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein 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 spasms, abdominal pain, abdominal pain associated with irritable bowel syndrome and / or visceral pain in a mammal. DETAILED DESCRIPTION

[0039] definition

[0040] Features, integers, characteristics, compounds, chemical moieties or groups described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein unless incompatible therewith. All features disclosed in this specification (including any accompanying claims, abstract and drawings) and / or all steps of any method or process disclosed thereby may be combined in any combination, except for combinations in which at least some of these features and / or steps are mutually exclusive. The invention is not limited to the details of any foregoing embodiments. The invention extends to any novel feature or any novel combination of features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel step or any novel combination of steps of any method or process disclosed thereby.

[0041] The term "alkyl" refers to a monovalent or polyvalent (e.g., monovalent or divalent) straight or branched chain saturated hydrocarbon group containing 1 to 12 carbon atoms. In some preferred embodiments, the alkyl group contains 1 to 6 carbon atoms ("C 1-6 -alkyl"), such as 1, 2, 3, 4, 5, or 6 carbon atoms. In other embodiments, the alkyl group contains 1 to 3 carbon atoms, such as 1, 2, or 3 carbon atoms. Some non-limiting examples of alkyl include methyl, ethyl, propyl, 2-propyl (isopropyl), n-butyl, isobutyl, sec-butyl, tert-butyl, and 2,2-dimethylpropyl. A particularly preferred but non-limiting example of an alkyl is methyl.

[0042] The term "alkoxy" refers to an alkyl group as defined above attached to the parent molecular moiety via an oxygen atom. Unless otherwise specified, an alkoxy group contains 1 to 12 carbon atoms. In some preferred embodiments, an alkoxy group contains 1 to 6 carbon atoms ("C 1-6-alkoxy"). In other embodiments, the alkoxy group contains 1 to 4 carbon atoms. In other embodiments, the alkoxy group contains 1 to 3 carbon atoms. Some non-limiting examples of alkoxy groups include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, and tert-butoxy. A particularly preferred but non-limiting example of alkoxy is methoxy.

[0043] The term "halogen" or "halo" refers to fluorine (F), chlorine (Cl), bromine (Br) or iodine (I). Preferably, the term "halogen" or "halo" refers to fluorine (F), chlorine (Cl) or bromine (Br). Particularly preferred but non-limiting examples of "halogen" or "halo" are fluorine (F) and chlorine (Cl).

[0044] As used herein, the term "cycloalkyl" refers to a ring of 3 to 10 carbon atoms ("C 3-10 In some preferred embodiments, the cycloalkyl group is a monocyclic hydrocarbon group of 3 to 8 ring carbon atoms. "Bicyclic cycloalkyl" refers to a cycloalkyl portion consisting of two saturated carbon rings with two common carbon atoms (i.e., the bridge separating the two rings is a single bond or a chain of one or two ring atoms) and a spirocyclic portion (i.e., the two rings are connected via a 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]heptane-2-yl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. Preferred but non-limiting examples of cycloalkyl include spiro[3.3]heptane-2-yl and cyclopropyl.

[0045] As used herein, 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 a heterocyclic moiety consisting of two rings with two common ring atoms (i.e., the bridge separating the two rings is a single bond or a chain of one or two ring atoms) and a spirocyclic moiety (i.e., the two rings are connected via 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-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 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.

[0046] 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 of 6 to 12 ring members and more preferably 6 to 10 ring members, and wherein at least one ring in the system is aromatic. Some non-limiting examples of aryl include phenyl and 9H-fluorenyl (e.g., 9H-fluoren-9-yl). A particularly preferred but non-limiting example of aryl is phenyl.

[0047] 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 in the system is aromatic, and at least one ring in the system contains one or more heteroatoms. Preferably, "heteroaryl" refers to a 5- to 10-membered heteroaryl containing 1, 2, 3 or 4 heteroatoms independently selected from O, S and N. More preferably, "heteroaryl" refers to a 5- to 10-membered heteroaryl containing 1 to 2 heteroatoms independently selected from O, S and N, such as a 5-, 6-, 7-, 8-, 9- or 10-membered heteroaryl. 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; pyridinyl (e.g., 2-pyridinyl); pyrazolyl (e.g., pyrazol-1-yl); triazolyl; tetrazolyl; pyrazinyl; imidazolyl (e.g., imidazolyl); benzoxazolyl (e.g., benzoxazolyl-2-yl), 2,3-dihydrobenzofuranyl; and oxazolo[5,4-c]pyridin-2-yl. Some particularly preferred but non-limiting examples of heteroaryl include oxadiazolyl; pyridinyl; triazolyl; tetrazolyl; pyrazinyl and imidazolyl.

[0048] The heterocyclic or heteroaryl ring may be attached to its pendant group at any heteroatom or carbon atom that results in the creation of a stable structure.

[0049] The term "hydroxyl" refers to an -OH group.

[0050] The term "amino" refers to the -NH 2 Group.

[0051] The term "cyano" refers to a -CN (nitrile) group.

[0052] The term "carbamyl" refers to the group -C(O)-NH 2 .

[0053] The term "oxo" refers to the group =0.

[0054] The term "carbonyl" refers to the group C=O.

[0055] The term "haloalkyl" refers to an alkyl group in which at least one hydrogen atom of the alkyl group has been replaced by a halogen atom, preferably fluorine. Preferably, "haloalkyl" refers to an alkyl group in which 1, 2 or 3 hydrogen atoms of the alkyl group have been replaced by a halogen atom, most preferably fluorine. 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.

[0056] The term "haloalkoxy" refers to an alkoxy group in which at least one hydrogen atom of the alkoxy group has been replaced by a halogen atom, preferably fluorine. Preferably, "haloalkoxy" refers to an alkoxy group in which 1, 2 or 3 hydrogen atoms of the alkoxy group have been replaced by a halogen atom, most preferably fluorine. Preferred but non-limiting examples of haloalkoxy are 2,2,2-trifluoro-1,1-dimethyl-ethoxy, 2,2,2-trifluoroethoxy and trifluoromethoxy.

[0057] The term "haloaryl" refers to an aryl group in which at least one hydrogen atom of the aryl group has been replaced by a halogen atom (preferably fluorine or chlorine). Preferably, "haloaryl" refers to an aryl group in which 1, 2 or 3 hydrogen atoms of the aryl group have been replaced by a halogen atom (most preferably fluorine). Preferred but non-limiting examples of haloaryl are 4-fluorophenyl, 2-chloro-4-fluorophenyl, 2,6-difluorophenyl and 3,5-difluorophenyl.

[0058] The term "aryloxy" means 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.

[0059] The term "cycloalkoxy" means a cycloalkyl group as defined above attached to the parent molecular moiety through an oxygen atom. A preferred but non-limiting example of a cycloalkoxy group is cyclopropyloxy.

[0060] 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 (eg 2-pyridyloxy, 3-pyridyloxy or 4-pyridyloxy).

[0061] The term "heterocyclyloxy" means a heterocyclyl group as defined above attached to the parent molecular moiety through an oxygen atom. A preferred but non-limiting example of aminoalkyl is azetidinyloxy.

[0062] The term "pharmaceutical salt" refers to those salts that retain the biological effect and properties of free alkali or free acid, which are not undesirable in biology or other aspects. These salts are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc. (particularly 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, methylsulfonic acid, ethylsulfonic acid, p-toluenesulfonic acid, salicylic acid, N-acetylcysteine, etc. In addition, these salts can be prepared by adding inorganic bases or organic bases to free acids. Salts derived from inorganic bases include but are not limited to sodium, potassium, lithium, ammonium, calcium, magnesium salts, etc. Salts derived from organic bases include, but are not limited to, salts of primary, secondary and tertiary amines, substituted amines (including naturally occurring substituted amines), cyclic amines and basic ion exchange resins (such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, lysine, arginine, N-ethylpiperidine, piperidine, polyimine resins, and the like). A particular pharmaceutically acceptable salt of the compound of formula (I) is the hydrochloride salt.

[0063] As used herein, the term "protecting group" (PG) represents a group that selectively blocks a reactive site in a multifunctional compound so that a chemical reaction selectively occurs on another unprotected reactive site that is usually associated therewith in synthetic chemistry. The protecting group can be removed at an appropriate point. Exemplary protecting groups are amino protecting groups, carboxyl protecting groups, or hydroxy protecting groups. Specific protecting groups are tert-butyloxycarbonyl (Boc), benzyloxycarbonyl (Cbz), fluorenylmethoxycarbonyl (Fmoc), and benzyl (Bn). Further specific protecting groups are tert-butyloxycarbonyl (Boc) and fluorenylmethoxycarbonyl (Fmoc). A more specific protecting group is tert-butyloxycarbonyl (Boc). Exemplary protecting groups and their use in organic synthesis are described in, for example, TW Greene and PGM Wutts, Protective Groups in Organic Chemistry, 5th edition, 2014, John Wiley & Sons, NY.

[0064] The term "urea forming agent" refers to a compound capable of converting a first amine into a substance that will react with a second amine to form a urea derivative. Non-limiting examples of urea forming agents include bis(trichloromethyl) carbonate, phosgene, trichloromethyl chloroformate, (4-nitrophenyl) carbonate, and 1,1'-carbonyldiimidazole. Urea forming agents are described by G. Sartori et al. (Green Chemistry 2000, 2, 140), which is incorporated herein by reference.

[0065] 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 diastereomers, mixtures of diastereomers, 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) as described herein, respectively.

[0066] According to the Cahn-Ingold-Prelog Convention, an asymmetric carbon atom can be in either the "R" or "S" configuration.

[0067] The abbreviation "MAGL" refers to monoacylglycerol lipase. The terms "MAGL" and "monoacylglycerol lipase" are used interchangeably herein.

[0068] As used herein, the term "treating" includes: (1) inhibiting a state, disorder or condition of at least one clinical or subclinical symptom of a disease (e.g., in the case of maintenance therapy, preventing, alleviating or delaying the development of a disease or its recurrence); and / or (2) relieving a condition (i.e., causing a state, disorder or condition of a disease or at least one clinical or subclinical symptom to subside). The benefit to the patient being treated is statistically significant or at least perceptible to the patient or physician. However, it should be understood that when a drug is administered to a patient to treat a disease, the result may not always be an effective treatment.

[0069] As used herein, the term "preventing" or "treatment" includes preventing or delaying the appearance of clinical symptoms of a state, disorder or condition that develops in a mammal, especially a human, that may have or is susceptible to the state, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disorder or condition.

[0070] As used herein, the term "neuroinflammation" refers to acute and chronic inflammation of nervous tissue, which is the main tissue component of two parts of the nervous system; the brain and spinal cord of the central nervous system (CNS) and the peripheral nerves of the peripheral nervous system (PNS). Chronic neuroinflammation is associated with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and multiple sclerosis. Acute neuroinflammation usually occurs immediately after injury to the central nervous system, for example, caused by traumatic brain injury (TBI).

[0071] As used herein, the term "traumatic brain injury" ("TBI", also referred to as "intracranial injury") refers to damage to the brain caused by external mechanical forces such as rapid acceleration or deceleration, impact, shock waves, or projectile penetration.

[0072] As used herein, the term "neurodegenerative disease" relates to diseases associated with progressive loss of structure or function of neurons, including neuronal death. Examples of neurodegenerative diseases include, but are not limited to, multiple sclerosis, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.

[0073] As used herein, the term "mental disorder" (also referred to as psychosis or mental illness) refers to a pattern of behavior or mind that may cause distress or poor functioning. Such features may be persistent, recurring, or remitted, or may be a single event. Examples of mental disorders include, but are not limited to, anxiety disorders and depression.

[0074] As used herein, the term "pain" refers to unpleasant sensory and emotional experiences associated with actual or potential tissue damage. Examples of pain include, but are not limited to, nociceptive pain, chronic pain (including idiopathic pain), neuropathic pain (including chemotherapy-induced neuropathy), phantom pain, and psychogenic pain. A specific example of pain is neuropathic pain, which is caused by damage or disease affecting any part of the nervous system involved in body sensation (i.e., the somatosensory system). In one embodiment, "pain" is neuropathic pain due to amputation or thoracotomy. In one embodiment, "pain" is chemotherapy-induced neuropathy.

[0075] As used herein, the term "neurotoxicity" refers to toxicity to the nervous system. This occurs when exposed to natural or artificial toxic substances (neurotoxins) that alter the normal activity of the nervous system, thereby causing damage to neural tissue. Examples of neurotoxicity include, but are not limited to, neurotoxicity caused by exposure to substances used in chemotherapy, radiation therapy, drug therapy, drug abuse, and organ transplantation, as well as exposure to heavy metals, certain foods and food additives, pesticides, industrial and / or cleaning solvents, cosmetics, and some natural substances.

[0076] As used herein, the term "cancer" refers to a disease characterized by the presence of a neoplasm or tumor due to abnormal, uncontrolled growth of cells (such cells are "cancer cells"). As used herein, the term cancer specifically includes, but is not limited to, hepatocellular carcinoma, colon carcinoma, and ovarian cancer.

[0077] As used herein, the term "mammal" includes humans and non-humans, and includes, but is not limited to, humans, non-human primates, dogs, cats, mice, cows, horses, and pigs. In particularly preferred embodiments, the term "mammal" refers to humans.

[0078] Compounds of the present invention

[0079] In a first aspect, the present invention provides a compound of formula (I)

[0080]

[0081] or a pharmaceutically acceptable salt thereof, wherein:

[0082] R 5 Selected from group 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 NH–;

[0083] R 1 Selected from hydrogen, halogen, SF 5 , Group Aminosulfonyl, (C 1-6 -alkyl) 2 PO-C 1-6 -alkyl-, group 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

[0084] R 2 Selected from 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

[0085] R 1 and R 2 Together with the atoms to which they are attached, they form 1-6 - a 3- to 14-membered heterocyclic ring substituted with an alkyl substituent;

[0086] R 2a is selected from hydrogen and halogen;

[0087] R 3 Selected from hydrogen and C 1-6 -alkyl;

[0088] R 4 Selected from hydrogen, hydroxyl, amino, group Group Aminosulfonyl, carboxyl, 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 -alkoxy-C(O)–;

[0089] R 4a Selected from hydrogen and C 1-6 -alkyl;

[0090] R 6 Selected from hydrogen, C 6-14 -Aryl and halo-C 6-14 - aryl;

[0091] R 7 Selected from C 1-6 -alkyl, cyano-C 1-6 -alkyl and halo-C 1-6 -alkyl;

[0092] R 8 Selected from hydrogen, halogen, cyano, hydroxyl, oxo, carboxyl, C 1-6 -Alkoxycarbonyl, C 1-6 -Alkyl, group Group Group 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 -alkyl-NHC(O)–;

[0093] R 9 Selected from hydrogen, halogen, hydroxyl, C 1-6 -alkyl and halo-C 1-6 -alkyl;

[0094] R 10 is selected from hydrogen and halogen;

[0095] R 11 is selected from the group consisting of hydrogen, methyl, cyclopropylmethyl and phenyl;

[0096] R 12 Selected from hydrogen, halogen, oxo, C 1-6 -alkyl, C 1-6 -alkoxycarbonyl and C 3-10 - cycloalkyl;

[0097] R 13 Selected from hydrogen, C 1-6 -alkyl and halo-C 1-6 -alkyl;

[0098] A is selected from C 6-14 -Aryl, C 3-10 - cycloalkyl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl;

[0099] B is selected from the group consisting of azetidinyl, piperidinyl, piperazinyl, 2-azaspiro[3.3]heptyl, 2,6-diazaspiro[3.3]heptyl, 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]heptyl;

[0100] C is selected from phenyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, 4,5-dihydroisoxazolyl, 2-azabicyclo[2.1.1]hexanyl, 2-azaspiro[3.3]heptanyl and 2,8-diazaspiro[3.5]nonanyl;

[0101] D is selected from C 6-14 -Aryl, C 3-10 - cycloalkyl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl;

[0102] E is selected from 5- to 14-membered heteroaryl, 3- to 14-membered heterocyclyl and C 3-10 - cycloalkyl;

[0103] F is selected from C 3-10 - cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 14-membered heteroaryl;

[0104] L is selected from a covalent bond, a carbonyl group, –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–, –NHC(O)–, –CH 2 NHC(O)– and

[0105] L 1 Selected from covalent bond, carbonyl, –CH 2 –, –CH 2 O–, –OCH 2 –, –NHCH 2 –, CH 2 NH–, –NR 11 –, –C(O)-NH-NH-C(O)-CH 2 –, –SO 2 – and –O–;

[0106] L 2 Select from covalent bonds and –SO 2 –

[0107] L 3 Select from covalent bonds, carbonyl groups and –CH 2 -;and

[0108] X is selected from O and NH.

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

[0110] R 5 Selected from group C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkyl, halo-C1-6 -alkoxy, C 1-6 -Alkyl-SO 2 –, C 1-6 -Alkyl-SO 2 NH–;

[0111] R 1 Selected from hydrogen, halogen, SF 5 , Group Aminosulfonyl, (C 1-6 -alkyl) 2 PO-C 1-6 -alkyl-, group 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

[0112] R 2 Selected from 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

[0113] R 1 and R 2 Together with the atoms to which they are attached, they form 1-6 - a 3- to 14-membered heterocyclic ring substituted with an alkyl substituent;

[0114] R 2a is selected from hydrogen and halogen;

[0115] R 3 Selected from hydrogen and C 1-6 -alkyl;

[0116] R 4 Selected from hydrogen, hydroxyl, amino, group Group Aminosulfonyl, carboxyl, hydroxy-C 1-6 -alkyl, C 1-6 -Alkyl-SO 2 NH–, carbamoyl, C 1-6 -alkyl-NHC(O)–, (C1-6 -alkyl) 2 NC(O)–, C 1-6 -alkyl-C(O)NH–, C 1-6 -alkoxy-C(O)NH– and C 1-6 -alkoxy-C(O)–;

[0117] R 4a Selected from hydrogen and C 1-6 -alkyl;

[0118] R 6 Selected from hydrogen, C 6-14 -Aryl and halo-C 6-14 - aryl;

[0119] R 7 Selected from C 1-6 -alkyl, cyano-C 1-6 -alkyl and halo-C 1-6 -alkyl;

[0120] R 8 is selected from hydrogen, halogen, cyano, hydroxyl, oxo, carboxyl, C 1-6 -Alkoxycarbonyl, C 1-6 -Alkyl, group Group Group 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 -alkyl-NHC(O)–;

[0121] R 9 Selected from hydrogen, halogen, hydroxyl, C 1-6 -alkyl and halo-C 1-6 -alkyl;

[0122] R 10 is selected from hydrogen and halogen;

[0123] R 11 is selected from hydrogen, methyl, cyclopropylmethyl and phenyl;

[0124] R 12 Selected from hydrogen, halogen, oxo, C 1-6 -alkyl, C1-6 -alkoxycarbonyl and C 3-10 - cycloalkyl;

[0125] R 13 Selected from hydrogen, C 1-6 -alkyl and halo-C 1-6 -alkyl;

[0126] A is selected from C 6-14 -Aryl, C 3-10 - cycloalkyl, 5- to 6-membered heteroaryl, and 3- to 14-membered heterocyclyl;

[0127] B is selected from the group consisting of azetidinyl, piperidinyl, piperazinyl, 2-azaspiro[3.3]heptyl, 2,6-diazaspiro[3.3]heptyl, 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]heptyl, the group and Group

[0128] C is selected from phenyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, 4,5-dihydroisoxazolyl, 2-azabicyclo[2.1.1]hexanyl, 2-azaspiro[3.3]heptanyl and 2,8-diazaspiro[3.5]nonanyl;

[0129] D is selected from C 6-14 -Aryl, C 3-10 - cycloalkyl, 5- to 6-membered heteroaryl, and 3- to 14-membered heterocyclyl;

[0130] E is selected from 5- to 14-membered heteroaryl, 3- to 14-membered heterocyclyl and C 3-10 - cycloalkyl;

[0131] F is selected from C 3-10 - cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 14-membered heteroaryl;

[0132] L is selected from a covalent bond, a carbonyl group, –CHR 6 –, –O–, –NR 11 –, –NHCH 2 –, –CH 2 NR 11 –、–N(CH 3 )CH 2 –, –OCH 2 –, –CH 2 O–, –CH2 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–, –NHC(O)–, –CH 2 NHC(O)– and

[0133] L 1 Selected from covalent bond, carbonyl, –CH 2 –, –CH 2 O–, –OCH 2 –, –NHCH 2 –, CH 2 NH–, –NR 11 –, –C(O)-NH-NH-C(O)-CH 2 –, –SO 2 – and –O–;

[0134] L 2 Select from covalent bonds and –SO 2 –

[0135] L 3 Select from covalent bonds, carbonyl groups and –CH 2 –

[0136] X is selected from O and NH;

[0137] Provided that when B is 2-azaspiro[3.3]heptyl or 2,6-diazaspiro[3.3]heptyl, L is not a covalent bond.

[0138] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein the compound of formula (I) is a compound of formula (II),

[0139]

[0140] Where R 1 To R 4 , R 2a , R 4a , A, B and L are as defined herein; and

[0141] p and q are each independently selected from 0 and 1.

[0142] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein the compound of formula (I) is a compound of formula (I-II),

[0143]

[0144] Where R 1 To R 4 , R 2a , R 4a , A, B and L are as defined herein.

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

[0146] R 5 Selected from group C 1-6 -Alkyl-SO 2 –, C 1-6 -Alkyl-SO 2 NH– and halo-C 1-6 - alkoxy;

[0147] R 1 Selected from hydrogen, halogen, SF 5 , Group Aminosulfonyl, (C 1-6 -alkyl) 2 PO-C 1-6 -alkyl-, group 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

[0148] R 2 Selected from 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

[0149] R 1 and R 2 Together with the atoms to which they are attached, they form a 1-6- a 3- to 14-membered heterocyclic ring substituted with an alkyl substituent;

[0150] R 2a is selected from hydrogen and halogen;

[0151] R 6 Selected from hydrogen, C 6-14 -Aryl and halo-C 6-14 - aryl;

[0152] R 7 Selected from C 1-6 -alkyl, cyano-C 1-6 -alkyl and halo-C 1-6 -alkyl;

[0153] R 8 Selected from hydrogen, halogen, cyano, hydroxyl, oxo, carboxyl, C 1-6 -Alkoxycarbonyl, C 1-6 -Alkyl, group Group Group 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 -alkyl-NHC(O)–;

[0154] R 9 Selected from hydrogen, halogen, hydroxyl, C 1-6 -alkyl and halo-C 1-6 -alkyl;

[0155] R 10 is selected from hydrogen and halogen;

[0156] R 11 is selected from the group consisting of hydrogen, methyl, cyclopropylmethyl and phenyl;

[0157] R 13 Selected from hydrogen, C 1-6 -alkyl and halo-C 1-6 -alkyl;

[0158] A is selected from C 6-14 -Aryl, C 3-10 - cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 14-membered heteroaryl;

[0159] D is selected from C 6-14 -Aryl, C 3-10 - cycloalkyl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl;

[0160] F is selected from C 3-10 - cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 14-membered heteroaryl;

[0161] L is selected from a covalent bond, –CHR 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 NHCH 2 –, –C(O)NH–, –NHC(O)–, –CH 2 NHC(O)– and

[0162] L 1 Selected from covalent bond, carbonyl, –CH 2 –, –CH 2 O–, –NHCH 2 –, CH 2 NH–, –NR 11 –, –C(O)-NH-NH-C(O)-CH 2 –, –SO 2 – and –O–;

[0163] L 3 Select from covalent bonds, carbonyl groups and –CH 2 -;and

[0164] X is selected from O and NH.

[0165] In one embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof, wherein:

[0166] R 5 Selected from group C 1-6 -Alkyl-SO 2 –, C 1-6 -Alkyl-SO 2 NH– and halo-C 1-6 - alkoxy;

[0167] R 1 Selected from hydrogen, halogen, SF 5 , Group Aminosulfonyl, (C 1-6 -alkyl) 2 PO-C 1-6 -alkyl-, group 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

[0168] R 2 Selected from 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

[0169] R 1 and R 2 Together with the atoms to which they are attached, they form a 1-6 - a 3- to 14-membered heterocyclic ring substituted with an alkyl substituent;

[0170] R 2a is selected from hydrogen and halogen;

[0171] R 6 Selected from hydrogen, C 6-14 -Aryl and halo-C 6-14 - aryl;

[0172] R 7 Selected from C 1-6 -alkyl, cyano-C 1-6 -alkyl and halo-C 1-6 -alkyl;

[0173] R 8 Selected from hydrogen, halogen, cyano, hydroxyl, oxo, carboxyl, C 1-6 -Alkoxycarbonyl, C1-6 -Alkyl, group Group Group 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 -alkyl-NHC(O)–;

[0174] R 9 Selected from hydrogen, halogen, hydroxyl, C 1-6 -alkyl and halo-C 1-6 -alkyl;

[0175] R 10 is selected from hydrogen and halogen;

[0176] R 11 is selected from hydrogen, methyl, cyclopropylmethyl and phenyl;

[0177] R 13 Selected from hydrogen, C 1-6 -alkyl and halo-C 1-6 -alkyl;

[0178] A is selected from C 6-14 -Aryl, C 3-10 - cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 6-membered heteroaryl;

[0179] D is selected from C 6-14 -Aryl, C 3-10 - cycloalkyl, 5- to 6-membered heteroaryl, and 3- to 14-membered heterocyclyl;

[0180] F is selected from C 3-10 - cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 14-membered heteroaryl;

[0181] L is selected from a covalent bond, –CHR 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 NHCH 2 –, –C(O)NH–, –NHC(O)–, –CH 2 NHC(O)– and

[0182] L 1 Selected from covalent bond, carbonyl, –CH 2 –, –CH 2 O–, –NHCH 2 –, CH 2 NH–, –NR 11 –, –C(O)-NH-NH-C(O)-CH 2 –, –SO 2 – and –O–;

[0183] L 3 Select from covalent bonds, carbonyl groups and –CH 2 -;and

[0184] X is selected from O and NH.

[0185] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein:

[0186] R 5 For group

[0187] R 1 Selected from halogen, C 1-6 -alkyl, halo-C 1-6 -Alkyl and group

[0188] R 2 is selected from hydrogen, halogen and halo-C 1-6 -alkyl;

[0189] R 2a is hydrogen;

[0190] R 8 and R 9 are each independently selected from halogen and halo-C 1-6 -alkyl;

[0191] R10 is hydrogen;

[0192] A is selected from C 6-14 -Aryl and C 3-10 - cycloalkyl;

[0193] D is selected from C 6-14 -Aryl and C 3-10 - cycloalkyl;

[0194] L is selected from a covalent bond, –O– and –CH 2 O–; and

[0195] L 1 It is a covalent bond.

[0196] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein:

[0197] R 5 For group

[0198] R 1 Selected from fluorine, chlorine, tert-butyl, CHF 2 CF 3 and Group

[0199] R 2 Selected from hydrogen, fluorine, chlorine and CF 3 ;

[0200] R 2a is hydrogen;

[0201] R 8 and R 9 Each independently selected from fluorine, chlorine and CF 3 ;

[0202] R 10 is hydrogen;

[0203] A is selected from phenyl and cyclopropyl;

[0204] D is selected from phenyl and cyclopropyl;

[0205] L is selected from a covalent bond, –O– and –CH 2 O–; and

[0206] L 1 It is a covalent bond.

[0207] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein:

[0208] B is selected from spiro[3.3]heptane-2-yl, azetidinyl and 7-azaspiro[3.5]nonan-7-yl; and

[0209] R 3 For hydrogen.

[0210] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein:

[0211] R 4 Selected from group and carbamoyl;

[0212] R 4a is hydrogen;

[0213] R 12 is selected from hydrogen and oxo;

[0214] C is pyrrolidinyl;

[0215] E is selected from 5-membered heteroaryl and 5-membered heterocyclyl; and

[0216] L 2 It is a covalent bond.

[0217] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein:

[0218] R 4 Selected from group and carbamoyl;

[0219] R 4a is hydrogen;

[0220] R 12 is selected from hydrogen and oxo;

[0221] C is pyrrolidinyl;

[0222] E is selected from the group consisting of imidazolyl, pyrazolyl, triazolyl and oxazolidinyl; and

[0223] L 2 It is a covalent bond.

[0224] In one embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof, wherein:

[0225] R 5 Selected from group C 1-6 -Alkyl-SO 2 –、C 1-6 -Alkyl-SO 2 NH– and halo-C 1-6 - alkoxy;

[0226] R 1 Selected from hydrogen, halogen, SF 5 , Group Aminosulfonyl, (C 1-6 -alkyl) 2 PO-C 1-6 -alkyl-, group 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

[0227] R 2 Selected from 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

[0228] R 1 and R 2 Together with the atoms to which they are attached, they form a 1-6 - a 3- to 14-membered heterocyclic ring substituted with an alkyl substituent;

[0229] R 2a is selected from hydrogen and halogen;

[0230] R 3 Selected from hydrogen and C 1-6 -alkyl;

[0231] R 4 Selected from hydrogen, hydroxyl, amino, group Group Aminosulfonyl, carboxyl, 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 -alkoxy-C(O)–;

[0232] R 4a Selected from hydrogen and C 1-6 -alkyl;

[0233] R 6 Selected from hydrogen, C 6-14 -Aryl and halo-C 6-14 - aryl;

[0234] R 7 Selected from C 1-6 -alkyl, cyano-C 1-6 -alkyl and halo-C 1-6 -alkyl;

[0235] R 8 is selected from hydrogen, halogen, cyano, hydroxyl, oxo, carboxyl, C 1-6 -Alkoxycarbonyl, C 1-6 -Alkyl, group Group Group 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 -alkyl-NHC(O)–;

[0236] R 9 Selected from hydrogen, halogen, hydroxyl, C 1-6 -alkyl and halo-C 1-6 -alkyl;

[0237] R 10 is selected from hydrogen and halogen;

[0238] R 11 is selected from hydrogen, methyl, cyclopropylmethyl and phenyl;

[0239] R 12 Selected from hydrogen, halogen, oxo, C 1-6 -alkyl, C 1-6 -alkoxycarbonyl and C 3-10 - cycloalkyl;

[0240] R 13 Selected from hydrogen, C 1-6 -alkyl and halo-C 1-6 -alkyl;

[0241] A is selected from C 6-14 -Aryl, C 3-10 - cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 14-membered heteroaryl;

[0242] B is selected from the group consisting of azetidinyl, piperidinyl, piperazinyl, 2-azaspiro[3.3]heptyl, 2,6-diazaspiro[3.3]heptyl, 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]heptyl;

[0243] C is selected from phenyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, 4,5-dihydroisoxazolyl, 2-azabicyclo[2.1.1]hexanyl, 2-azaspiro[3.3]heptanyl and 2,8-diazaspiro[3.5]nonanyl;

[0244] D is selected from C 6-14 -Aryl, C 3-10 - cycloalkyl, 5- to 14-membered heteroaryl, and 3- to 14-membered heterocyclyl;

[0245] E is selected from 5- to 14-membered heteroaryl, 3- to 14-membered heterocyclyl and C 3-10 - cycloalkyl;

[0246] F is selected from C 3-10 - cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 14-membered heteroaryl;

[0247] L is selected from a covalent bond, –CHR 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 2NH–, –SO 2 NHCH 2 –, –C(O)NH–, –NHC(O)–, –CH 2 NHC(O)– and

[0248] L 1 Selected from covalent bond, carbonyl, –CH 2 –, –CH 2 O–, –NHCH 2 –, CH 2 NH–, –NR 11 –, –C(O)-NH-NH-C(O)-CH 2 –, –SO 2 – and –O–;

[0249] L 2 Select from covalent bonds and –SO 2 –

[0250] L 3 Select from covalent bonds, carbonyl groups and –CH 2 -;and

[0251] X is selected from O and NH.

[0252] In one embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof, wherein:

[0253] R 5 Selected from group C 1-6 -Alkyl-SO 2 –、C 1-6 -Alkyl-SO 2 NH– and halo-C 1-6 - alkoxy;

[0254] R 1 Selected from hydrogen, halogen, SF 5 , Group Aminosulfonyl, (C 1-6 -alkyl) 2 PO-C 1-6 -alkyl-, group 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

[0255] R 2 Selected from 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

[0256] R 1 and R 2 Together with the atoms to which they are attached, they form a 1-6 - a 3- to 14-membered heterocyclic ring substituted with an alkyl substituent;

[0257] R 2a is selected from hydrogen and halogen;

[0258] R 3 Selected from hydrogen and C 1-6 -alkyl;

[0259] R 4 Selected from hydrogen, hydroxyl, amino, group Group Aminosulfonyl, carboxyl, 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 -alkoxy-C(O)–;

[0260] R 4a Selected from hydrogen and C 1-6 -alkyl;

[0261] R 6 Selected from hydrogen, C 6-14 -Aryl and halo-C 6-14 - aryl;

[0262] R 7 Selected from C 1-6 -alkyl, cyano-C 1-6 -alkyl and halo-C 1-6 -alkyl;

[0263] R 8 is selected from hydrogen, halogen, cyano, hydroxyl, oxo, carboxyl, C 1-6-Alkoxycarbonyl, C 1-6 -Alkyl, group Group Group 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 -alkyl-NHC(O)–;

[0264] R 9 Selected from hydrogen, halogen, hydroxyl, C 1-6 -alkyl and halo-C 1-6 -alkyl;

[0265] R 10 is selected from hydrogen and halogen;

[0266] R 11 is selected from the group consisting of hydrogen, methyl, cyclopropylmethyl and phenyl;

[0267] R 12 Selected from hydrogen, halogen, oxo, C 1-6 -alkyl, C 1-6 -alkoxycarbonyl and C 3-10 - cycloalkyl;

[0268] R 13 Selected from hydrogen, C 1-6 -alkyl and halo-C 1-6 -alkyl;

[0269] A is selected from C 6-14 -Aryl, C 3-10 - cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 6-membered heteroaryl;

[0270] B is selected from the group consisting of azetidinyl, piperidinyl, piperazinyl, 2-azaspiro[3.3]heptyl, 2,6-diazaspiro[3.3]heptyl, 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]heptyl, the group and Group

[0271] C is selected from phenyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, 4,5-dihydroisoxazolyl, 2-azabicyclo[2.1.1]hexanyl, 2-azaspiro[3.3]heptanyl and 2,8-diazaspiro[3.5]nonanyl;

[0272] D is selected from C 6-14 -Aryl, C 3-10 - cycloalkyl, 5- to 6-membered heteroaryl, and 3- to 14-membered heterocyclyl;

[0273] E is selected from 5- to 14-membered heteroaryl, 3- to 14-membered heterocyclyl and C 3-10 - cycloalkyl;

[0274] F is selected from C 3-10 - cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 14-membered heteroaryl;

[0275] L is selected from a covalent bond, –CHR 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 NHCH 2 –, –C(O)NH–, –NHC(O)–, –CH 2 NHC(O)– and

[0276] L 1 Selected from covalent bond, carbonyl, –CH 2 –, –CH 2 O–, –NHCH 2 –, CH 2 NH–, –NR 11 –, –C(O)-NH-NH-C(O)-CH 2 –, –SO 2 – and –O–;

[0277] L 2 Select from covalent bonds and –SO 2 –

[0278] L 3 Select from covalent bonds, carbonyl groups and –CH 2 -;and

[0279] X is selected from O and NH.

[0280] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein:

[0281] R 5 For group

[0282] R 1 Selected from halogen, C 1-6 -alkyl, halo-C 1-6 -Alkyl and group

[0283]

[0284] R 2 is selected from hydrogen, halogen and halo-C 1-6 -alkyl;

[0285] R 2a is hydrogen;

[0286] R 3 is hydrogen;

[0287] R 4 Selected from group and carbamoyl;

[0288] R 4a is hydrogen;

[0289] R 8 and R 9 are each independently selected from halogen and halo-C 1-6 -alkyl;

[0290] R 10 is hydrogen;

[0291] R 12 is selected from hydrogen and oxo;

[0292] A is selected from C 6-14 -Aryl and C 3-10 - cycloalkyl;

[0293] B is selected from spiro[3.3]heptan-2-yl, azetidinyl and 7-azaspiro[3.5]nonan-7-yl;

[0294] C is pyrrolidinyl;

[0295] D is selected from C 6-14 -Aryl and C 3-10 - cycloalkyl;

[0296] E is selected from 5-membered heteroaryl and 5-membered heterocyclyl;

[0297] L is selected from a covalent bond, –O– and –CH 2 O–;

[0298] L 1 is a covalent bond; and

[0299] L 2 It is a covalent bond.

[0300] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein:

[0301] R 5 For group

[0302] R 1 Selected from fluorine, chlorine, tert-butyl, CHF 2 CF 3 and Group

[0303] R 2 Selected from hydrogen, fluorine, chlorine and CF 3 ;

[0304] R 2a is hydrogen;

[0305] R 3 is hydrogen;

[0306] R 4 Selected from group and carbamoyl;

[0307] R 4a is hydrogen;

[0308] R 8 and R 9 Each independently selected from fluorine, chlorine and CF 3 ;

[0309] R 10 is hydrogen;

[0310] R 12 is selected from hydrogen and oxo;

[0311] A is selected from phenyl and cyclopropyl;

[0312] B is selected from spiro[3.3]heptan-2-yl, azetidinyl and 7-azaspiro[3.5]nonan-7-yl;

[0313] C is pyrrolidinyl;

[0314] D is selected from phenyl and cyclopropyl;

[0315] E is selected from the group consisting of imidazolyl, pyrazolyl, triazolyl and oxazolidinyl;

[0316] L is selected from a covalent bond, –O– and –CH 2 O–;

[0317] L 1 is a covalent bond; and

[0318] L 2 It is a covalent bond.

[0319] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 5 Selected from group C 1-6 -Alkyl-SO 2 –, C 1-6 -Alkyl-SO 2 NH– and halo-C 1-6 -alkoxy; wherein R 1 , R 2 , A and L are as described herein.

[0320] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 1 Selected from hydrogen, halogen, SF 5 , Group Aminosulfonyl, (C 1-6 -alkyl) 2 PO-C 1-6 -alkyl-, group 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-; where R 7 To R 10 , X, D and L 1 As defined herein.

[0321] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 1 and R 2 Together with the atoms to which they are attached, they form 1-6 - a 3- to 14-membered heterocyclic ring substituted with an alkyl substituent.

[0322] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein L is selected from a covalent bond, -CHR 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 NHCH 2 –, –C(O)NH–, –NHC(O)–, –CH 2 NHC(O)– and Where R 6 and R 11 As defined herein.

[0323] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is azetidinyl.

[0324] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is piperidinyl.

[0325] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is piperazinyl.

[0326] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is 2-azaspiro[3.3]heptyl.

[0327] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is 2,6-diazaspiro[3.3]heptyl.

[0328] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is 2-azaspiro[3.4]octanyl.

[0329] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is 6-azaspiro[3.4]octanyl.

[0330] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is 2,7-diazaspiro[3.4]octanyl.

[0331] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is 8-azabicyclo[3.2.1]octanyl.

[0332] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is 2,7-diazaspiro[3.5]nonanyl.

[0333] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is 2-azaspiro[3.5]nonanyl.

[0334] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is 7-azaspiro[3.5]nonanyl.

[0335] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is 1,2,3,3a,4,5,6,6a-octahydrocyclopenta[c]pyrrolyl.

[0336] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is cyclobutyl.

[0337] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is a cubic alkyl group.

[0338] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is bicyclo[1.1.1]pentanyl.

[0339] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is spiro[3.3]heptyl.

[0340] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein C is phenyl.

[0341] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein C is azetidinyl.

[0342] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein C is pyrrolidinyl.

[0343] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein C is piperidinyl.

[0344] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein C is piperazinyl.

[0345] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein C is morpholinyl.

[0346] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein C is 4,5-dihydroisoxazolyl.

[0347] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein C is 2-azabicyclo[2.1.1]hexanyl.

[0348] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein C is 2-azaspiro[3.3]heptyl.

[0349] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein C is 2,8-diazaspiro[3.5]nonanyl.

[0350] 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.

[0351] 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]heptyl and C is pyrrolidinyl.

[0352] 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]heptyl and C is pyrrolidinyl.

[0353] 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.

[0354] 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.

[0355] 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.

[0356] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein B is 2-azaspiro[3.4]octanyl and C is pyrrolidinyl.

[0357] 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.

[0358] In one embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof, wherein B is piperidinyl and C is pyrrolidinyl.

[0359] In one embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof, wherein both B and C are azetidinyl.

[0360] 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.

[0361] 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.

[0362] 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 piperidinyl.

[0363] 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.

[0364] 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]heptyl and C is piperidinyl.

[0365] 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.

[0366] 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 piperidinyl.

[0367] 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.

[0368] In one embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof, wherein B is cubic alkyl and C is pyrrolidinyl.

[0369] 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.

[0370] 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.

[0371] 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.

[0372] 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.

[0373] 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.

[0374] 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.

[0375] 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.

[0376] In one embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein L 1 Selected from covalent bond, carbonyl, –CH 2 –, –CH 2 O–, –NHCH 2 –, CH 2 NH–, –NR 11 –, –C(O)-NH-NH-C(O)-CH 2 –, –SO 2 – and –O–.

[0377] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 5 For the group Where R 1 , R 2 , A and L are as defined herein.

[0378] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 1 Selected from halogen, C 1-6 -alkyl, halo-C 1-6 -Alkyl and group Where R 8 To R 10 , D and L 1 As defined herein.

[0379] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 2 is selected from hydrogen, halogen and halo-C 1-6 -alkyl.

[0380] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 2a For hydrogen.

[0381] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 3 For hydrogen.

[0382] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 4 Selected from group and carbamoyl.

[0383] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 4a For hydrogen.

[0384] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 8 and R 9 are each independently selected from halogen and halo-C 1-6 -alkyl.

[0385] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 10 For hydrogen.

[0386] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 12 is selected from hydrogen and oxo.

[0387] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein A is selected from C 6-14 -Aryl and C 3-10 -cycloalkyl.

[0388] 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]heptane-2-yl, azetidinyl and 7-azaspiro[3.5]nonan-7-yl.

[0389] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein D is selected from C 6-14 -Aryl and C 3-10 -cycloalkyl.

[0390] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein E is selected from a 5-membered heteroaryl group and a 5-membered heterocyclic group.

[0391] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein L is selected from a covalent bond, -O- and -CH 2 O–.

[0392] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein L 1 It is a covalent bond.

[0393] In a preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein L 2 It is a covalent bond.

[0394] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 1 Selected from fluorine, chlorine, tert-butyl, CHF 2 CF 3 and Group

[0395] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 2 Selected from hydrogen, fluorine, chlorine and CF 3 .

[0396] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein R 8 and R 9 Each independently selected from fluorine, chlorine and CF 3 .

[0397] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein A is selected from phenyl and cyclopropyl.

[0398] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein A is phenyl.

[0399] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein A is cyclopropyl.

[0400] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein D is selected from phenyl and cyclopropyl.

[0401] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein D is phenyl.

[0402] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein D is cyclopropyl.

[0403] In a particularly preferred embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof, wherein E is selected from imidazolyl, pyrazolyl, triazolyl and oxazolidinyl.

[0404] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein E is imidazolyl.

[0405] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein E is pyrazolyl.

[0406] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein E is triazolyl.

[0407] In a particularly preferred embodiment, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein, wherein E is oxazolidinyl.

[0408] In one embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof, which is selected from:

[0409] [3-[[2-Fluoro-6-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0410] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0411] 4-[1-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidin-3-yl]oxazolidin-2-one;

[0412] (+)- or (-)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0413] (-)- or (+)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0414] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(4-methyl-1H-pyrazol-5-yl)azetidin-1-yl]methanone;

[0415] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)azetidin-1-yl]methanone;

[0416] [4-[(2-chloro-4-fluoro-phenyl)methoxy]-1-piperidinyl]-[3-(4-methyl-1H-pyrazol-5-yl)azetidin-1-yl]methanone;

[0417] [4-[(4-chloro-2-fluoro-phenoxy)methyl]-1-piperidinyl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0418] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)-1-piperidinyl]methanone;

[0419] [6-(2-Chloro-4-fluoro-phenoxy)-2-azaspiro[3.3]heptane-2-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0420] [3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]-[4-[[4-(trifluoromethyl)phenyl]methyl]-1-piperidinyl]methanone;

[0421] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(2-methylpyrazol-3-yl)pyrrolidin-1-yl]methanone;

[0422] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)phenyl]methanone;

[0423] [3-[[2-Fluoro-4-(pentafluoro-λ 6 -thio)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0424] (+)- or (-)-[3-[[2-fluoro-6-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0425] (-)- or (+)-[3-[[2-fluoro-6-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0426] [3-[4-(2,4-dichlorophenyl)phenyl]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0427] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0428] 6-[1-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidin-3-yl]-1H-pyridin-2-one;

[0429] 6-[1-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidin-3-yl]-1H-pyrazin-2-one;

[0430] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(4-isopropyl-1H-pyrazol-3-yl)pyrrolidin-1-yl]methanone;

[0431] 4-[1-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidin-3-yl]oxazolidin-2-one;

[0432] 5-[1-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidin-3-yl]-1H-pyrazole-4-carboxylic acid ethyl ester;

[0433] 5-[1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidin-3-yl]pyrrolidin-2-one;

[0434] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3R)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0435] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0436] 1-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0437] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0438] [3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone;

[0439] [3-(4-tert-Butylphenyl)azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0440] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1,2,4-triazol-1-yl)pyrrolidin-1-yl]methanone;

[0441] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-(3-imidazol-1-ylpyrrolidin-1-yl)methanone;

[0442] [3-[[2,4-bis(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0443] (+)- 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;

[0444] (-)- 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;

[0445] (+)- or (-)-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]-[3-(4-tetrahydropyran-4-ylphenyl)azetidin-1-yl]methanone;

[0446] (-)- or (+)-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]-[3-(4-tetrahydropyran-4-ylphenyl)azetidin-1-yl]methanone;

[0447] (+)- or (-)-[3-(4-isopropoxyphenyl)azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0448] (-)- or (+)-[3-(4-isopropoxyphenyl)azetidin-1-yl]-[(3S)-3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0449] (+)- 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;

[0450] (-)- 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;

[0451] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-imidazol-5-yl)pyrrolidin-1-yl]methanone;

[0452] (+)- 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;

[0453] (-)- 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;

[0454] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-imidazol-2-yl)pyrrolidin-1-yl]methanone;

[0455] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0456] Sodium [3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[rac-(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0457] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0458] (+)- or (-)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-imidazol-1-ylpyrrolidin-1-yl]methanone;

[0459] (-)- or (+)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-imidazol-1-ylpyrrolidin-1-yl]methanone;

[0460] [3-[[3-Chloro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0461] [3-[[2-Chloro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0462] (+)- or (-)-[3-[2-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0463] (-)- or (+)-[3-[2-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0464] (+)- or (-)-[3-(4-propoxyphenyl)azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0465] (-)- or (+)-[3-(4-propoxyphenyl)azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0466] (+)- or (-)-[3-[[2,4-bis(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0467] (-)- or (+)-[3-[[2,4-bis(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0468] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-tetrazol-5-yl)pyrrolidin-1-yl]methanone;

[0469] (+)- or (-)-1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]-N-methyl-pyrrolidine-3-carboxamide;

[0470] (-)- or (+)-1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]-N-methyl-pyrrolidine-3-carboxamide;

[0471] (+)- or (-)-1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]-N,N-dimethyl-pyrrolidine-3-carboxamide;

[0472] (-)- or (+)-1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]-N,N-dimethyl-pyrrolidine-3-carboxamide;

[0473] (+)- or (-)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-pyrazol-1-ylpyrrolidin-1-yl]methanone;

[0474] (-)- or (+)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-pyrazol-1-ylpyrrolidin-1-yl]methanone;

[0475] (+)- or (-)-1-[3-[4-(2,4-difluorophenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0476] (-)- or (+)-1-[3-[4-(2,4-difluorophenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0477] [3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]-[3-(4-THF-3-ylphenyl)azetidin-1-yl]methanone;

[0478] [3-(4-tert-Butylphenyl)azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0479] [3-[2-[2-Fluoro-4-(trifluoromethyl)phenyl]ethyl]azetidin-1-yl]-[(3S)-3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0480] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(triazol-1-yl)pyrrolidin-1-yl]methanone;

[0481] [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptane-2-yl]-[(3S)-3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0482] [3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]-[3-(4-tetrahydropyran-3-ylphenyl)azetidin-1-yl]methanone;

[0483] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-(3-pyrrol-1-ylpyrrolidin-1-yl)methanone;

[0484] trans-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]cyclobutyl]-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0485] (+)- 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;

[0486] (-)- 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;

[0487] (-)- or (+)-[3-[4-(2,4-difluorophenyl)phenyl]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0488] (+)- or (-)-[3-[4-(2,4-difluorophenyl)phenyl]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0489] [3-[4-(2,4-difluorophenyl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0490] [4-[Bis(4-fluorophenyl)methyl]-1-piperidinyl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0491] 4-[1-[3-[3-chloro-4-(trifluoromethoxy)phenyl]azetidine-1-carbonyl]pyrrolidin-3-yl]oxazolidin-2-one;

[0492] [3-[4-(2-methylazetidin-1-yl)phenyl]azetidin-1-yl]-[(3S or 3R)-3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0493] [3-[4-(2-methylazetidin-1-yl)phenyl]azetidin-1-yl]-[(3R or 3S)-3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0494] [3-[4-(3-fluoropyrrolidin-1-yl)phenyl]azetidin-1-yl]-[(3R or 3S)-3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0495] (+)- or (-)-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone;

[0496] (-)- or (+)-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone;

[0497] (+)- or (-)-[3-[[2-chloro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0498] (-)- or (+)-[3-[[2-chloro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0499] [3-[4-(3-fluoropyrrolidin-1-yl)phenyl]azetidin-1-yl]-[(3S or 3R)-3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0500] 4-[1-[3-[4-(2,2,2-trifluoroethyl)phenyl]azetidine-1-carbonyl]pyrrolidin-3-yl]oxazolidin-2-one;

[0501] [3-[4-(Oxetane-3-yl)phenyl]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0502] (+)- or (-)-[3-[4-(oxetan-3-yl)phenyl]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0503] (-)- or (+)-[3-[4-(oxetan-3-yl)phenyl]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0504] 4-[1-[3-[4-(2,4-difluorophenyl)phenyl]azetidine-1-carbonyl]pyrrolidin-3-yl]oxazolidin-2-one;

[0505] [3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone;

[0506] [4-[Bis(4-fluorophenyl)methyl]-1-piperidinyl]-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0507] 4-[1-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-carbonyl]pyrrolidin-3-yl]oxazolidin-2-one;

[0508] (+)- or (-)-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone;

[0509] (-)- or (+)-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone;

[0510] (+)- or (-)-[3-(3,3-dimethyl-2H-benzofuran-6-yl)azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0511] (-)- or (+)-[3-(3,3-dimethyl-2H-benzofuran-6-yl)azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone;

[0512] (+)- or (-)-[4-[bis(4-fluorophenyl)methyl]-1-piperidinyl]-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0513] (-)- or (+)-[4-[bis(4-fluorophenyl)methyl]-1-piperidinyl]-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0514] [3-[[2-Chloro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0515] [(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-(2,2,2-trifluoro-1,1-dimethyl-ethoxy)phenyl]azetidin-1-yl]methanone;

[0516] [3-[[2-Fluoro-4-(pentafluoro-λ 6 -thio)phenyl]methoxy]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0517] [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0518] (+)-[4-[(2-chloro-4-fluoro-phenoxy)methyl]-1-piperidinyl]-[(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0519] (-)-[4-[(2-chloro-4-fluoro-phenoxy)methyl]-1-piperidinyl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0520] (+)- 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;

[0521] (-)- 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;

[0522] (+)- or (-)-[4-[[2-chloro-4-(trifluoromethyl)phenyl]methoxy]-1-piperidinyl]-[(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0523] (-)- or (+)-[4-[[2-chloro-4-(trifluoromethyl)phenyl]methoxy]-1-piperidinyl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0524] [(3R or 3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[[4-(trifluoromethyl)phenyl]methyl]pyrrolidin-1-yl]methanone;

[0525] [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;

[0526] [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;

[0527] [(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;

[0528] [(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;

[0529] (-)-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3R or 3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0530] (+)-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3R or 3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0531] (-)-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3R or 3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0532] (+)-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3S or 3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0533] (-)-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3S or 3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0534] (+)-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3S or 3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0535] [3-[6-(2-chlorophenoxy)-3-pyridinyl]azetidin-1-yl]-[3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0536] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]methanone;

[0537] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3R)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]methanone;

[0538] [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;

[0539] [6-(2-Chloro-4-fluoro-phenoxy)-2-azaspiro[3.3]heptane-2-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[0540] [3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridinyl]azetidin-1-yl]methanone;

[0541] [(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;

[0542] [(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;

[0543] [6-(2-Chloro-4-fluoro-phenoxy)-2-azaspiro[3.3]heptane-2-yl]-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]methanone;

[0544] [(3R)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[6-[6-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.3]heptane-2-yl]methanone;

[0545] [(3R)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridinyl]azetidin-1-yl]methanone;

[0546] [3-[4-(4-fluorophenoxy)phenyl]azetidin-1-yl]-[3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0547] [3-(Tetrazol-1-yl)pyrrolidin-1-yl]-[6-[6-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.3]heptane-2-yl]methanone;

[0548] [3-(Tetrazol-1-yl)pyrrolidin-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridinyl]azetidin-1-yl]methanone;

[0549] (+)- 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;

[0550] (-)- 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;

[0551] (+)- 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;

[0552] (-)- 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;

[0553] (+)- or (-)-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridinyl]azetidin-1-yl]methanone;

[0554] (-)- or (+)-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridinyl]azetidin-1-yl]methanone;

[0555] (+)- or (-)-[3-[4-(4-fluorophenoxy)phenyl]azetidin-1-yl]-[3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0556] (-)- or (+)-[3-[4-(4-fluorophenoxy)phenyl]azetidin-1-yl]-[3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0557] (+)- or (-)-[3-(tetrazolyl-1-yl)pyrrolidin-1-yl]-[6-[6-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.3]heptane-2-yl]methanone;

[0558] (-)- or (+)-[3-(tetrazolyl-1-yl)pyrrolidin-1-yl]-[6-[6-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.3]heptane-2-yl]methanone;

[0559] (+)- or (-)-[3-(tetrazol-1-yl)pyrrolidin-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridinyl]azetidin-1-yl]methanone;

[0560] (-)- or (+)-[3-(tetrazol-1-yl)pyrrolidin-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridinyl]azetidin-1-yl]methanone;

[0561] [(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[2-(3,3,3-trifluoropropoxy)spiro[3.3]heptane-6-yl]methanone;

[0562] [(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone;

[0563] [3-[4-(4-Fluorophenoxy)phenyl]azetidin-1-yl]-[(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0564] [(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-[3-(2,2,2-trifluoroethoxy)azetidin-1-yl]phenyl]azetidin-1-yl]methanone;

[0565] [6-(2-Chloro-4-fluoro-phenoxy)-2-azaspiro[3.3]heptane-2-yl]-[(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0566] [(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridinyl]azetidin-1-yl]methanone;

[0567] [(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[6-[3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridinyl]azetidin-1-yl]methanone;

[0568] [3-[2-(3-chlorophenyl)ethynyl]azetidin-1-yl]-[(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0569] [3-[2-[2-(Difluoromethyl)phenyl]ethynyl]azetidin-1-yl]-[(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0570] [4-(3-Cyclopropyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]-[rac-(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0571] [(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;

[0572] [(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;

[0573] [(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;

[0574] [(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;

[0575] [(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[2-(3,3,3-trifluoropropoxy)spiro[3.3]heptane-6-yl]methanone;

[0576] [2-[[1-(Difluoromethyl)cyclopropyl]methoxy]spiro[3.3]heptane-6-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0577] [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;

[0578] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[3-(triazol-1-yl)pyrrolidin-1-yl]methanone;

[0579] [3-[4-[3-(2,2-dimethylpropyl)triazol-4-yl]phenyl]azetidin-1-yl]-[3-(triazol-1-yl)pyrrolidin-1-yl]methanone;

[0580] [3-(Triazol-1-yl)pyrrolidin-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone;

[0581] [3-(2-Chloro-4-isopropylsulfonyl-phenyl)azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0582] [3-(4-tert-Butylsulfonyl-2-chloro-phenyl)azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0583] [3-[5-(2-chlorophenoxy)pyrazin-2-yl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0584] [(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[6-[6-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.3]heptane-2-yl]methanone;

[0585] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0586] [(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone;

[0587] [3-[6-(2,4-dichlorophenoxy)-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0588] [3-[4-(4-Fluorophenoxy)phenyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0589] [3-(2-Chloro-4-isobutylsulfonyl-phenyl)azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0590] [3-[4-(Benzenesulfonyl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0591] [3-(2-Chloro-4-propylsulfonyl-phenyl)azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0592] [3-[4-(2-chloro-4-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0593] [3-(4-tert-Butylphenyl)azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0594] 1-[3-[4-(2-chloro-4-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0595] [3-(5-tert-Butyl-2-pyridyl)azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0596] 1-[3-[4-(2-chloro-4-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxylic acid;

[0597] 1-[3-[4-(2,4-difluorophenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxylic acid;

[0598] 2-[4-[1-[(3S)-3-(1H-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]sulfonylacetonitrile;

[0599] [3-[4-(N-methylanilino)phenyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0600] [(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-(trifluoromethylsulfonyl)phenyl]azetidin-1-yl]methanone;

[0601] [3-(4-cyclohexylsulfonylphenyl)azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0602] 1-[5-[1-[(3S)-3-(1H-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]-2-pyridinyl]cyclobutanecarbonitrile;

[0603] [6-[(2,4-difluorophenyl)methyl]-2,6-diazaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0604] [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;

[0605] [3-[4-[N-(Cyclopropylmethyl)anilino]phenyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0606] 1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0607] [3-[4-(N-phenylanilino)phenyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0608] [3-(6-tert-butyl-3-pyridyl)azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0609] [3-[6-[(5-methoxy-2-pyridinyl)-methyl-amino]-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0610] [3-[6-[(5-ethyl-2-pyridinyl)-methyl-amino]-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0611] [3-[6-[(5-Cyclopropyl-2-pyridinyl)-methyl-amino]-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0612] [3-[4-(N-methylanilino)phenyl]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0613] [3-[6-(N-methylanilino)-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0614] [3-[6-(4-isopropyl-N-methyl-anilino)-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0615] [3-[6-[(3-ethyl-2-pyridinyl)-methyl-amino]-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0616] [3-[6-[N-(Cyclopropylmethyl)anilino]-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0617] (3S)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0618] (3R)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0619] [3-[6-[N-(cyclopropylmethyl)anilino]-3-pyridinyl]azetidin-1-yl]-[3-(1H-tetrazolyl-5-yl)pyrrolidin-1-yl]methanone;

[0620] [3-(1H-tetrazolyl-5-yl)pyrrolidin-1-yl]-[3-[4-(2,2,2-trifluoro-1,1-dimethyl-ethoxy)phenyl]azetidin-1-yl]methanone;

[0621] [2-(2-methoxyphenyl)sulfonyl-2,6-diazaspiro[3.3]heptane-6-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0622] [2-[4-Fluoro-2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptane-6-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0623] [2-(2,2-dimethylpropylsulfonyl)-2,6-diazaspiro[3.3]heptane-6-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0624] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[0625] [2-[4-Fluoro-2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptane-6-yl]-[(3R)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[0626] [2-[4-Fluoro-2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptane-6-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[0627] [3-[6-[N-(Cyclopropylmethyl)anilino]-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(1H-tetrazolyl-5-yl)pyrrolidin-1-yl]methanone;

[0628] [3-[6-[N-(Cyclopropylmethyl)anilino]-3-pyridinyl]azetidin-1-yl]-[(3R)-3-(1H-tetrazolyl-5-yl)pyrrolidin-1-yl]methanone;

[0629] [3-[4-(4-fluorophenoxy)phenyl]azetidin-1-yl]-[3-(1H-tetrazol-5-yl)pyrrolidin-1-yl]methanone;

[0630] 1-[3-[6-[N-(cyclopropylmethyl)anilino]-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0631] [3-[4-(4-fluorophenoxy)phenyl]azetidin-1-yl]-[(3R)-3-(1H-tetrazolyl-5-yl)pyrrolidin-1-yl]methanone;

[0632] [3-[4-(4-Fluorophenoxy)phenyl]azetidin-1-yl]-[(3S)-3-(1H-tetrazol-5-yl)pyrrolidin-1-yl]methanone;

[0633] [(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[3-[4-[4-(trifluoromethyl)pyrimidin-2-yl]oxyphenyl]azetidin-1-yl]methanone;

[0634] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[3-(1H-tetrazolyl-5-yl)pyrrolidin-1-yl]methanone;

[0635] [(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[6-[6-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.3]heptane-2-yl]methanone;

[0636] [(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-2-azaspiro[3.3]heptane-2-yl]methanone;

[0637] (3S)-1-[3-[6-[N-(cyclopropylmethyl)anilino]-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0638] (3R)-1-[3-[6-[N-(cyclopropylmethyl)anilino]-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0639] [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;

[0640] [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[4-[3-(trifluoromethyl)azetidin-1-yl]phenyl]azetidin-1-yl]methanone;

[0641] 1-[3-[4-(Benzenesulfonyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0642] [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;

[0643] 1-[3-[4-[3-(2,2,2-trifluoroethoxy)azetidin-1-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0644] [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;

[0645] [3-[(2-Fluoro-4-methylsulfonyl-phenyl)methoxy]azetidin-1-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[0646] 1-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0647] 1-[3-[4-[3-(trifluoromethyl)azetidin-1-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0648] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3R)-3-(1H-tetrazolyl-5-yl)pyrrolidin-1-yl]methanone;

[0649] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-tetrazolyl-5-yl)pyrrolidin-1-yl]methanone;

[0650] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]methanone;

[0651] [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;

[0652] [3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]azetidin-1-yl]methanone;

[0653] [3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[[5-(trifluoromethyl)-3-pyridinyl]methoxy]azetidin-1-yl]methanone;

[0654] [3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[6-[[5-(trifluoromethyl)-3-pyridinyl]oxy]-2-azaspiro[3.3]heptan-2-yl]methanone;

[0655] [6-[(5-chloro-3-pyridinyl)oxy]-2-azaspiro[3.3]heptan-2-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[0656] [6-[(6-chloro-3-pyridinyl)oxy]-2-azaspiro[3.3]heptan-2-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[0657] (3S)-1-[3-[4-[3-(2,2,2-trifluoroethoxy)azetidin-1-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0658] (3R)-1-[3-[4-[3-(2,2,2-trifluoroethoxy)azetidin-1-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0659] (3S)-1-[3-[4-(phenylsulfonyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0660] (3R)-1-[3-[4-(phenylsulfonyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0661] [3-[(2-Fluoro-4-methylsulfonyl-phenyl)methoxy]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0662] 2-Cyclopropyl-6-[1-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]oxy-benzonitrile;

[0663] (3S)-1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0664] (3S)-1-[2-[2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptane-6-carbonyl]pyrrolidine-3-carboxamide;

[0665] (3S)-1-[3-[[[3-(Trifluoromethyl)phenyl]sulfonylamino]methyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0666] (3S)-1-[3-[[[4-(Trifluoromethyl)phenyl]sulfonylamino]methyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0667] (3S)-1-[6-[[1-(Trifluoromethyl)cyclopropyl]methoxy]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[0668] (3S)-1-[6-[[6-(trifluoromethyl)-3-pyridinyl]oxy]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[0669] (3S)-1-[6-[[5-(trifluoromethyl)-2-pyridinyl]methyl]-2,6-diazaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[0670] (3S)-1-[3-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0671] (3S)-1-[3-[[5-(trifluoromethyl)-3-pyridinyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0672] (3S)-1-[6-[[[1-(Trifluoromethyl)cyclopropyl]amino]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[0673] [3-[4-(3-chloropyridazin-4-yl)oxyphenyl]azetidin-1-yl]-[(3R)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0674] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0675] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[0676] [3-[(2-Fluoro-4-methylsulfonyl-phenyl)methoxy]azetidin-1-yl]-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]methanone;

[0677] [(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[2-[2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptane-6-yl]methanone;

[0678] 1-[4-[1-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]cyclopropanecarbonitrile;

[0679] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]methanone;

[0680] N-[2-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptane-6-yl]-1-(trifluoromethyl)cyclopropanecarboxamide;

[0681] [(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[3-[4-[[1-(trifluoromethyl)cyclopropyl]methylamino]phenyl]azetidin-1-yl]methanone;

[0682] (3S)-1-[3-[2-[1-(trifluoromethyl)cyclopropyl]pyrimidin-5-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0683] (3S)-1-[3-[6-[1-(trifluoromethyl)cyclopropyl]-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0684] [3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[[2-(trifluoromethyl)pyrimidin-5-yl]methoxy]azetidin-1-yl]methanone;

[0685] 1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-N-methyl-pyrrolidine-3-carboxamide;

[0686] 1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-N-ethyl-pyrrolidine-3-carboxamide;

[0687] (3S)-1-[3-[4-[[1-(trifluoromethyl)cyclopropyl]amino]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0688] (3S)-1-[3-[4-[[1-(trifluoromethyl)cyclopropyl]methylamino]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0689] (3S)-1-[3-[(2-Fluoro-4-methylsulfonyl-phenyl)methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0690] (3S)-1-[2-(2,4-difluorophenyl)sulfonyl-2,6-diazaspiro[3.3]heptane-6-carbonyl]pyrrolidine-3-carboxamide;

[0691] (3S)-1-[2-[3-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptane-6-carbonyl]pyrrolidine-3-carboxamide;

[0692] (3S)-1-[2-[3-(trifluoromethoxy)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptane-6-carbonyl]pyrrolidine-3-carboxamide;

[0693] rac-(3S)-1-[3-[5-[3-(trifluoromethyl)pyrrolidin-1-yl]-2-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0694] (3S)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-N-methyl-pyrrolidine-3-carboxamide;

[0695] (3R)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-N-methyl-pyrrolidine-3-carboxamide;

[0696] (3S)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-N-ethyl-pyrrolidine-3-carboxamide;

[0697] (3R)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-N-ethyl-pyrrolidine-3-carboxamide;

[0698] [3-[6-(2-chlorophenoxy)-3-pyridinyl]azetidin-1-yl]-[(3R)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0699] [3-[4-(4-fluorophenoxy)phenyl]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0700] [3-[5-(2-chlorophenoxy)pyrazin-2-yl]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0701] [(3R)-3-(Tetrazol-1-yl)pyrrolidin-1-yl]-[6-[6-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.3]heptane-2-yl]methanone;

[0702] 2-Cyclopropyl-6-[1-[(3R)-3-(tetrazol-1-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]oxy-benzonitrile;

[0703] [3-[5-(2-chlorophenoxy)pyrazin-2-yl]azetidin-1-yl]-[(3R)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0704] [(3S)-3-(Tetrazol-1-yl)pyrrolidin-1-yl]-[6-[6-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.3]heptane-2-yl]methanone;

[0705] [3-[4-[3-(2,2-dimethylpropyl)triazol-4-yl]phenyl]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0706] [3-[4-(4-fluorophenoxy)phenyl]azetidin-1-yl]-[(3R)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0707] [3-[5-(2,4-dichlorophenoxy)pyrazin-2-yl]azetidin-1-yl]-[(3R)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0708] 2-Cyclopropyl-6-[1-[(3S)-3-(tetrazol-1-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]oxy-benzonitrile;

[0709] 2,2-dimethyl-3-[3-[1-[(3R)-3-(tetrazol-1-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]oxyphenyl]propanoic acid methyl ester;

[0710] [3-[6-(2-chlorophenoxy)-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0711] [3-[4-(4-cyclopropylpyrimidin-2-yl)oxyphenyl]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0712] [3-[5-(2,4-dichlorophenoxy)pyrazin-2-yl]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0713] 1-[4-[1-[(3R)-3-(tetrazolyl-1-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]cyclopropanecarbonitrile;

[0714] [3-[4-(4-cyclopropylpyrimidin-2-yl)oxyphenyl]azetidin-1-yl]-[(3R)-3-(tetrazolyl-1-yl)pyrrolidin-1-yl]methanone;

[0715] 1-[4-[1-[(3S)-3-(tetrazolyl-1-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]cyclopropanecarbonitrile;

[0716] 2,2-dimethyl-3-[3-[1-[(3S)-3-(tetrazol-1-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]oxyphenyl]propanoic acid methyl ester;

[0717] [3-[4-[3-(2,2-dimethylpropyl)triazol-4-yl]phenyl]azetidin-1-yl]-[(3R)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0718] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3R)-3-hydroxypyrrolidin-1-yl]methanone;

[0719] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3R)-3-(hydroxymethyl)pyrrolidin-1-yl]methanone;

[0720] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(hydroxymethyl)pyrrolidin-1-yl]methanone;

[0721] (3S)-1-[6-[[5-(Trifluoromethyl)pyrazin-2-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[0722] [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;

[0723] [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;

[0724] [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;

[0725] [6-[[2-Fluoro-4-(trifluoromethyl)phenyl]methylamino]-2-azaspiro[3.3]heptane-2-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[0726] (3S)-1-[3-[4-[3-(methylsulfonylmethyl)azetidin-1-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0727] rac-(3S)-1-[3-[5-[3-(trifluoromethyl)pyrrolidin-1-yl]pyrazin-2-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0728] [(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[3-[4-[3-(trifluoromethyl)azetidin-1-yl]phenyl]azetidin-1-yl]methanone;

[0729] [6-[[2-Fluoro-4-(trifluoromethyl)phenyl]methylamino]-2-azaspiro[3.3]heptane-2-yl]-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]methanone;

[0730] [6-[(4,4-difluoro-1-piperidinyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[0731] [3-[(4,4-difluorocyclohexyl)methoxy]azetidin-1-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[0732] N-[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptane-6-yl]-1-(trifluoromethyl)cyclopropanecarboxamide;

[0733] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-[[1-(trifluoromethyl)cyclopropyl]amino]phenyl]azetidin-1-yl]methanone;

[0734] 1-[4-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]cyclopropanecarbonitrile;

[0735] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[6-[1-(trifluoromethyl)cyclopropyl]-3-pyridinyl]azetidin-1-yl]methanone;

[0736] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[2-[1-(trifluoromethyl)cyclopropyl]pyrimidin-5-yl]azetidin-1-yl]methanone;

[0737] [3-[(2-Fluoro-4-methylsulfonyl-phenyl)methoxy]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0738] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[6-(trifluoromethyl)-3-pyridinyl]oxy]-2-azaspiro[3.3]heptan-2-yl]methanone;

[0739] [(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;

[0740] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[2-[2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptane-6-yl]methanone;

[0741] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[2-[3-(trifluoromethoxy)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptane-6-yl]methanone;

[0742] N-methyl-2-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2,6-diazaspiro[3.3]heptane-6-yl]methyl]benzamide;

[0743] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[2-[3-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptane-6-yl]methanone;

[0744] [(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[3-[2-[1-(trifluoromethyl)cyclopropyl]pyrimidin-5-yl]azetidin-1-yl]methanone;

[0745] N-[[1-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]methyl]-3-(trifluoromethyl)benzenesulfonamide;

[0746] [3-[4-(3-dimethylphosphorylphenyl)phenyl]azetidin-1-yl]-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]methanone;

[0747] [(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[6-(trifluoromethyl)pyridazin-3-yl]oxyazetidin-1-yl]methanone;

[0748] 1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-sulfonamide;

[0749] tert-Butyl N-[(3S)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidin-3-yl]carbamate;

[0750] (3S)-1-[3-[5-(2-chloro-4-methylsulfonyl-phenyl)-2-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0751] N-[[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]methyl]-3-(trifluoromethyl)benzenesulfonamide;

[0752] N-[[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]methyl]-4-(trifluoromethyl)benzenesulfonamide;

[0753] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[2-[4-(trifluoromethoxy)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptane-6-yl]methanone;

[0754] [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;

[0755] (3S)-1-[3-[5-(4-chloro-2-methylsulfonyl-phenyl)-2-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0756] (3S)-1-[3-[5-(2-chloro-4-methylsulfonyl-phenyl)pyrazin-2-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0757] (3R)-1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0758] (3R)-1-[6-[[6-(trifluoromethyl)-3-pyridinyl]oxy]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[0759] (3S)-1-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0760] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0761] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3R)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0762] 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;

[0763] [(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[6-[[[1-(trifluoromethyl)cyclopropyl]amino]methyl]-2-azaspiro[3.3]heptane-2-yl]methanone;

[0764] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3R)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0765] [3-[4-(Benzenesulfonyl)phenyl]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0766] [(3S)-3-(Tetrazol-1-yl)pyrrolidin-1-yl]-[3-[4-[4-(trifluoromethyl)pyrimidin-2-yl]oxyphenyl]azetidin-1-yl]methanone;

[0767] [3-[6-(2-chlorophenoxy)pyridazin-3-yl]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0768] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0769] 2-methyl-2-[3-[1-[(3S)-3-(tetrazol-1-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]oxyphenyl]propanoic acid methyl ester;

[0770] [2-[4-Fluoro-2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptane-6-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0771] 2-methyl-2-[3-[1-[(3R)-3-(tetrazol-1-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]oxyphenyl]propanoic acid methyl ester;

[0772] [(3R)-3-(Tetrazol-1-yl)pyrrolidin-1-yl]-[3-[4-[4-(trifluoromethyl)pyrimidin-2-yl]oxyphenyl]azetidin-1-yl]methanone;

[0773] [2-[4-Fluoro-3-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptane-6-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0774] [3-[(2-Fluoro-4-methylsulfonyl-phenyl)methoxy]azetidin-1-yl]-[(3S)-3-(tetrazolyl-1-yl)pyrrolidin-1-yl]methanone;

[0775] [2-[4-Fluoro-2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptane-6-yl]-[(3R)-3-(tetrazolyl-1-yl)pyrrolidin-1-yl]methanone;

[0776] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0777] [3-[4-(Dimethylphosphorylmethyl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0778] [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;

[0779] (3S)-1-[3-[4-(2-chloro-4-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0780] [3-[4-(2-chloro-4-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-hydroxypyrrolidin-1-yl]methanone;

[0781] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-hydroxypyrrolidin-1-yl]methanone;

[0782] (3S)-1-[3-[4-(6-chloro-4-methylsulfonyl-3-pyridinyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0783] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0784] (3-pyrrolidin-1-ylsulfonylpyrrolidin-1-yl)-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone;

[0785] Morpholino-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone;

[0786] [3-[5-(4-Chloro-2-fluoro-phenoxy)pyrazin-2-yl]azetidin-1-yl]-morpholino-methanone;

[0787] [3-[[rac-(1S,5R)-6,6-difluoro-3-bicyclo[3.1.0]hexyl]methoxy]azetidin-1-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[0788] [6-[[2-Fluoro-4-(trifluoromethyl)phenyl]methylamino]-2-azaspiro[3.3]heptane-2-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[0789] [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;

[0790] [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;

[0791] [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;

[0792] [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;

[0793] (3S)-1-[3-[5-(4-chloro-2-fluoro-phenyl)pyrimidin-2-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0794] (3S)-1-[3-[5-(4-chloro-2-fluoro-phenyl)-2-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0795] (3S)-1-[3-[5-(2,4-dichlorophenyl)-2-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0796] (3S)-1-[3-[4-(5-chloro-3-methylsulfonyl-2-pyridinyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0797] (3S)-1-[3-[6-(2-chloro-4-methylsulfonyl-phenyl)-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0798] (3S)-1-[3-[6-(4-chloro-2-methylsulfonyl-phenyl)-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0799] [3-[4-(6-chloro-4-methylsulfonyl-3-pyridinyl)phenyl]azetidin-1-yl]-[(3S)-3-hydroxypyrrolidin-1-yl]methanone;

[0800] (3S)-1-[3-[4-[5-(trifluoromethyl)pyrazin-2-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0801] [(3S)-3-Aminopyrrolidin-1-yl]-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]methanone;

[0802] [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;

[0803] [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;

[0804] (3S)-1-[7-[[2-Fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[0805] (3R)-1-[7-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[0806] (3S)-1-[7-[2-fluoro-4-(trifluoromethyl)phenoxy]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[0807] (3R)-1-[7-[2-fluoro-4-(trifluoromethyl)phenoxy]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[0808] (3S)-1-[2-[[2-Fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonane-7-carbonyl]pyrrolidine-3-carboxamide;

[0809] (3R)-1-[2-[[2-Fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonane-7-carbonyl]pyrrolidine-3-carboxamide;

[0810] [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;

[0811] (3S)-1-[7-[2-fluoro-4-(trifluoromethyl)phenyl]sulfonyl-2,7-diazaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[0812] [6-[(3,5-difluoro-2-pyridinyl)methyl]-2-azaspiro[3.3]heptane-2-yl]-[(3S)-3-(tetrazolyl-1-yl)pyrrolidin-1-yl]methanone;

[0813] [(3S)-3-(Tetrazol-1-yl)pyrrolidin-1-yl]-[6-[[6-(trifluoromethyl)-3-pyridinyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[0814] [6-[(5-fluoro-3-pyridinyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(tetrazolyl-1-yl)pyrrolidin-1-yl]methanone;

[0815] [6-[(3,5-difluoro-2-pyridinyl)methyl]-2-azaspiro[3.3]heptane-2-yl]-[(3R)-3-(tetrazolyl-1-yl)pyrrolidin-1-yl]methanone;

[0816] [(3R)-3-(Tetrazol-1-yl)pyrrolidin-1-yl]-[6-[[6-(trifluoromethyl)-3-pyridinyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[0817] [6-[(5-fluoro-3-pyridinyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3R)-3-(tetrazolyl-1-yl)pyrrolidin-1-yl]methanone;

[0818] [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;

[0819] N-[2-[3-(4H-1,2,4-triazol-3-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.5]nonan-7-yl]-3-(trifluoromethoxy)benzenesulfonamide;

[0820] (3S)-1-[3-[4-(4-chloro-2-fluoro-phenyl)-3-methylsulfonyl-phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0821] N-[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptane-6-yl]-2-(trifluoromethyl)benzenesulfonamide;

[0822] N-[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptane-6-yl]-3-(trifluoromethyl)benzenesulfonamide;

[0823] N-[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptane-6-yl]-4-(trifluoromethyl)benzenesulfonamide;

[0824] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[5-(trifluoromethyl)-2-pyridinyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[0825] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[6-(trifluoromethyl)-3-pyridinyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[0826] [(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;

[0827] (3S)-1-[6-[[2-(trifluoromethyl)phenyl]sulfonylamino]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[0828] (3S)-1-[6-[[3-(Trifluoromethyl)phenyl]sulfonylamino]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[0829] (3S)-1-[6-[[4-(Trifluoromethyl)phenyl]sulfonylamino]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[0830] (3S)-1-[6-(2,2-dimethylpropylsulfonylamino)-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[0831] (3S)-1-[3-[5-(2-chloro-4-methylsulfonyl-phenyl)pyrimidin-2-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0832] (3S)-1-[3-[2-(2-chloro-4-methylsulfonyl-phenyl)pyrimidin-5-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0833] [3-[6-(1,1-dioxo-1,4-thiazin-4-yl)-3-pyridinyl]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0834] [3-[5-(4-chloro-2-methylsulfonyl-phenyl)-2-pyridinyl]azetidin-1-yl]-[(3R)-3-hydroxypyrrolidin-1-yl]methanone;

[0835] [3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[6-[[6-(trifluoromethyl)-3-pyridinyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[0836] 1-[6-[[6-(Trifluoromethyl)-3-pyridinyl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-sulfonamide;

[0837] 1-[6-[[6-(Trifluoromethyl)-3-pyridinyl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]piperidine-3-carboxamide;

[0838] [3-[5-(4-chlorophenoxy)pyrazin-2-yl]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0839] [(3S)-3-(Tetrazol-1-yl)pyrrolidin-1-yl]-[6-[4-(trifluoromethyl)phenyl]-2-azaspiro[3.3]heptane-2-yl]methanone;

[0840] [(3S)-3-(Tetrazol-1-yl)pyrrolidin-1-yl]-[6-[2-(trifluoromethyl)pyrimidin-5-yl]-2-azaspiro[3.3]heptane-2-yl]methanone;

[0841] [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;

[0842] [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;

[0843] [(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[3-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-3-pyridinyl]azetidin-1-yl]methanone;

[0844] [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;

[0845] [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;

[0846] [(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;

[0847] (3R)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-sulfonamide;

[0848] (3S)-1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-sulfonamide;

[0849] 3-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-4,5-dihydroisoxazole-5-carboxamide;

[0850] 1-[7-[[2-Fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonane-2-carbonyl]piperidine-3-carboxamide;

[0851] 1-[7-[[2-Fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-sulfonamide;

[0852] [6-[(3-Methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0853] [6-[(4-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptane-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0854] (3S)-1-[6-[(3-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[0855] (3S)-1-[6-[(4-methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[0856] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-3-pyridinyl]azetidin-1-yl]methanone;

[0857] (3S)-1-[3-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0858] 4-Fluoro-N-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-4-piperidinyl]benzenesulfonamide;

[0859] N-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-4-piperidinyl]-4-(trifluoromethyl)benzenesulfonamide;

[0860] (3S)-1-[4-[[4-(trifluoromethyl)phenyl]sulfonylamino]piperidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0861] 4-Chloro-N-[[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-4-piperidinyl]methyl]benzenesulfonamide;

[0862] (3S)-1-[7-(4-Fluoro-2-methylsulfonyl-phenoxy)-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[0863] (3S)-1-[7-[6-(trifluoromethyl)pyridazin-3-yl]oxy-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[0864] (3S)-1-[7-[2-(trifluoromethyl)pyrimidin-4-yl]oxy-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[0865] (3S)-1-[7-[[3-(trifluoromethoxy)phenyl]sulfonylamino]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[0866] N-[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.5]nonan-7-yl]-3-(trifluoromethoxy)benzenesulfonamide;

[0867] (5S)-3-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-4,5-dihydroisoxazole-5-carboxamide;

[0868] (5R)-3-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-4,5-dihydroisoxazole-5-carboxamide;

[0869] 1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]azetidine-3-sulfonamide;

[0870] 1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]piperidine-4-sulfonamide;

[0871] N-[[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-4-piperidinyl]methyl]-4-(trifluoromethyl)benzenesulfonamide;

[0872] (3S)-1-[4-[[[4-(Trifluoromethyl)phenyl]sulfonylamino]methyl]piperidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0873] N-[[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-4-piperidinyl]methyl]-4-(trifluoromethoxy)benzenesulfonamide;

[0874] (3S)-1-[4-[[[4-(trifluoromethoxy)phenyl]sulfonylamino]methyl]piperidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0875] (3S)-1-[3-[4-(6,6-difluoro-2-azaspiro[3.3]heptan-2-yl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0876] (3S)-1-[3-[4-[3-(trifluoromethyl)cyclobutyl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0877] (3S)-1-[3-[4-(2-azaspiro[3.4]octan-2-yl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0878] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-2-azaspiro[3.3]heptane-2-yl]methanone;

[0879] [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;

[0880] [3-[6-(3-Hydroxy-3-methyl-azetidin-1-yl)-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0881] [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;

[0882] [3-[6-[3-Hydroxy-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridinyl]azetidin-1-yl]-[rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0883] [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;

[0884] [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;

[0885] (3S)-1-[6-[[1-(Trifluoromethyl)cyclopropyl]methylamino]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[0886] (3S)-1-[6-[(4-Fluoro-2-methylsulfonyl-phenyl)methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[0887] (3S)-1-[3-[6-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0888] rac-(3S)-1-[3-[6-[3-hydroxy-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0889] (3S)-1-[3-[4-[1-(2-tert-butyltetrazol-5-yl)cyclopropyl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0890] (3S)-1-[6-[[1-(Trifluoromethyl)cyclopropyl]amino]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[0891] [(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;

[0892] (3S)-1-[3-[6-[(3R)-3-hydroxy-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0893] (3S)-1-[3-[6-[(3S)-3-hydroxy-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0894] [3-[4-(4-fluorophenoxy)phenyl]azetidin-1-yl]-[(3R)-3-(tetrazol-2-yl)pyrrolidin-1-yl]methanone;

[0895] [(3R)-3-(Tetrazol-2-yl)pyrrolidin-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone;

[0896] [3-[6-[(3R)-3-hydroxy-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0897] [3-[6-[(3S)-3-hydroxy-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0898] [3-[6-(4-chloro-2-methylsulfonyl-phenoxy)-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]methanone;

[0899] 1-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-sulfonamide;

[0900] 1-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-sulfonamide;

[0901] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[[4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidin-1-yl]methanone;

[0902] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[[3-(trifluoromethylsulfonyl)phenyl]methoxy]azetidin-1-yl]methanone;

[0903] Methyl 2-[4-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]benzoate;

[0904] 1-[4-[1-[rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]piperidine-2-carboxamide;

[0905] [3-[[2-Fluoro-5-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0906] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[[4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]methanone;

[0907] [(3S)-3-(Tetrazol-1-yl)pyrrolidin-1-yl]-[3-[2-[1-(trifluoromethyl)cyclopropyl]pyrimidin-5-yl]azetidin-1-yl]methanone;

[0908] (3S)-1-[7-[[5-(Trifluoromethyl)pyrazin-2-yl]amino]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[0909] (3R)-1-[7-[[5-(Trifluoromethyl)pyrazin-2-yl]amino]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[0910] (3S)-1-[7-[5-(trifluoromethyl)pyrimidin-2-yl]oxy-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[0911] [3-[4-(4-Fluorophenoxy)phenyl]azetidin-1-yl]-[(3S)-3-(tetrazol-2-yl)pyrrolidin-1-yl]methanone;

[0912] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(tetrazol-2-yl)pyrrolidin-1-yl]methanone;

[0913] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3R)-3-(tetrazol-2-yl)pyrrolidin-1-yl]methanone;

[0914] [(3S)-3-(Tetrazol-1-yl)pyrrolidin-1-yl]-[3-[4-[[1-(trifluoromethyl)cyclopropyl]methoxy]phenyl]azetidin-1-yl]methanone;

[0915] [(3S)-3-(Tetrazol-1-yl)pyrrolidin-1-yl]-[3-[4-[5-(trifluoromethyl)pyrazin-2-yl]oxyphenyl]azetidin-1-yl]methanone;

[0916] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[6-[[1-(trifluoromethyl)cyclopropyl]amino]-3-pyridinyl]azetidin-1-yl]methanone;

[0917] 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;

[0918] (3S)-1-[7-[5-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[0919] [3-[[5-Chloro-2-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0920] [3-[[3-Chloro-5-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0921] [3-[[2-Fluoro-4-(trifluoromethoxy)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0922] [3-[[3-Fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0923] [3-[[2-Chloro-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0924] 2-[4-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]benzoic acid;

[0925] (3S)-1-[3-[4-(3,5-dimethylpyrazol-1-yl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0926] [6-[(3-Methylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptane-2-yl]-[(3S)-3-(tetrazolyl-1-yl)pyrrolidin-1-yl]methanone;

[0927] [3-[[2-Chloro-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0928] [3-[[3-Fluoro-4-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0929] [3-[[2-Fluoro-4-(trifluoromethoxy)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0930] [3-[[5-Chloro-2-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0931] [3-[[3-Chloro-5-(trifluoromethyl)phenyl]methylamino]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0932] [(3S)-3-(Tetrazol-1-yl)pyrrolidin-1-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-2-pyridinyl]azetidin-1-yl]methanone;

[0933] (3S)-1-[3-[6-(2-azaspiro[3.4]octan-2-yl)-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0934] 1-[3-[6-(2-azaspiro[3.4]octan-2-yl)-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-sulfonamide;

[0935] 1-[4-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]piperidine-2-carboxamide;

[0936] (3S)-1-[7-[[6-(trifluoromethyl)-3-pyridinyl]methyl]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[0937] 2-[4-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]benzamide;

[0938] (3S)-1-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methyl-methyl-amino]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0939] (3S)-1-[3-[[4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0940] (3S)-1-[3-[[3-(trifluoromethylsulfonyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0941] (3S)-1-[3-[5-[6-(trifluoromethyl)-3-pyridinyl]-1,2,4-oxadiazol-3-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0942] (3S)-1-[3-[5-[3-(trifluoromethyl)-1-bicyclo[1.1.1]pentyl]-1,2,4-oxadiazol-3-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0943] rac-(3S)-1-[3-[6-[3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0944] N-ethyl-2-[4-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]benzamide;

[0945] [3-[Cyclopropylmethyl-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]amino]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0946] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-(3-hydroxyazetidin-1-yl)methanone;

[0947] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-(3-hydroxy-3-methyl-azetidin-1-yl)methanone;

[0948] 1-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]azetidine-3-carboxamide;

[0949] 1-[3-[4-[5-(trifluoromethyl)pyrimidin-2-yl]oxyphenyl]azetidine-1-carbonyl]azetidine-3-carboxamide;

[0950] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methyl-methyl-amino]azetidin-1-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone;

[0951] (3S)-1-[3-(5-spiro[3.3]heptane-2-ylpyrazin-2-yl)azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0952] (3S)-1-[3-[4-[4-methyl-2-(pyrrolidine-1-carbonyl)phenyl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0953] (3S)-1-[6-[[6-(trifluoromethyl)-3-pyridinyl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[0954] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[3-(methylsulfonimide)pyrrolidin-1-yl]methanone;

[0955] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methyl-methyl-amino]azetidin-1-yl]-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]methanone;

[0956] N-[1-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-carbonyl]azetidin-3-yl]methanesulfonamide;

[0957] N-[1-[3-[4-[[1-(trifluoromethyl)cyclopropyl]methoxy]phenyl]azetidine-1-carbonyl]azetidin-3-yl]methanesulfonamide;

[0958] N-[1-[3-[4-[5-(trifluoromethyl)pyrazin-2-yl]oxyphenyl]azetidine-1-carbonyl]azetidin-3-yl]methanesulfonamide;

[0959] N-[1-[3-[6-[3-(trifluoromethyl)azetidin-1-yl]-3-pyridyl]azetidine-1-carbonyl]azetidin-3-yl]methanesulfonamide;

[0960] (3S)-1-[3-[3-[5-(2,2-dimethylpropyl)-1,3,4-oxadiazol-2-yl]-1-bicyclo[1.1.1]pentyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0961] [3-[3-[5-(2,2-dimethylpropyl)-1,3,4-oxadiazol-2-yl]-1-bicyclo[1.1.1]pentyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[0962] (3S)-1-[3-[4-[3-(2,2-dimethylpropyl)triazol-4-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0963] rac-(3S)-1-[3-[6-(2,2-difluoro-5-azaspiro[2.4]heptan-5-yl)-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0964] [(3S)-3-(Tetrazol-1-yl)pyrrolidin-1-yl]-[6-[[6-(trifluoromethyl)pyridazin-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone;

[0965] tert-Butyl 2-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methyl-methyl-amino]azetidine-1-carbonyl]-2,8-diazaspiro[3.5]nonane-8-carboxylate;

[0966] N-[1-[2-[[2-Fluoro-4-(trifluoromethyl)phenyl]methyl]-2,7-diazaspiro[3.5]nonane-7-carbonyl]azetidin-3-yl]methanesulfonamide;

[0967] (3S)-1-[3-[6-(6-oxa-2-azaspiro[3.4]octan-2-yl)-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0968] (3S)-1-[3-[6-(5-oxa-2-azaspiro[3.4]octan-2-yl)-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0969] [7-[[6-(Difluoromethoxy)-3-pyridinyl]methyl]-2-azaspiro[3.5]nonan-2-yl]-[(3S)-3-(tetrazolyl-1-yl)pyrrolidin-1-yl]methanone;

[0970] [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptane-2-yl]-[(3S)-3-(tetrazolyl-1-yl)pyrrolidin-1-yl]methanone;

[0971] [6-[[2-Fluoro-4-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptane-2-yl]-[(3S)-3-(tetrazolyl-1-yl)pyrrolidin-1-yl]methanone;

[0972] [6-[[4-Fluoro-2-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptane-2-yl]-[(3S)-3-(tetrazolyl-1-yl)pyrrolidin-1-yl]methanone;

[0973] N-[1-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-carbonyl]azetidin-3-yl]acetamide;

[0974] N-[1-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]azetidin-3-yl]acetamide;

[0975] N-[1-[7-[[1-(Trifluoromethyl)cyclopropyl]methoxy]-2-azaspiro[3.5]nonane-2-carbonyl]azetidin-3-yl]acetamide;

[0976] N-[1-[3-[4-[5-(trifluoromethyl)pyrazin-2-yl]oxyphenyl]azetidine-1-carbonyl]azetidin-3-yl]acetamide;

[0977] (3S)-1-[3-[6-[(3R)-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0978] (3S)-1-[3-[6-[(3S)-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0979] (3S)-1-[3-[4-[5-(trifluoromethyl)pyrazin-2-yl]oxyphenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0980] (3S)-1-[3-[5-[[1-(trifluoromethyl)cyclopropyl]methylamino]-2-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0981] (3S)-1-[3-[5-[[1-(trifluoromethyl)cyclopropyl]methylamino]pyrazin-2-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0982] (3S)-1-[3-[6-[3-(trifluoromethyl)azetidin-1-yl]-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0983] (3S)-1-[3-[2-[3-(trifluoromethyl)azetidin-1-yl]pyrimidin-5-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0984] (3S)-1-[7-[(3,5-difluoro-2-pyridinyl)methyl]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[0985] (3S)-1-[7-[(5-chloro-2-pyridinyl)methyl]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[0986] (3S)-1-[7-[[5-(Trifluoromethyl)pyrazin-2-yl]methyl]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[0987] (3S)-1-[7-[[5-(trifluoromethyl)-2-pyridinyl]methyl]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[0988] (3S)-1-[7-[[6-(difluoromethoxy)-3-pyridinyl]methyl]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[0989] (3S)-1-[6-[[6-(trifluoromethyl)pyridazin-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[0990] (3S)-1-[6-[[2-(trifluoromethyl)pyrimidin-5-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[0991] (3S)-1-[(6S)-6-[5-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.4]octane-2-carbonyl]pyrrolidine-3-carboxamide;

[0992] [6-(4-Fluorophenyl)-2-azaspiro[3.3]heptane-2-yl]-[(3S)-3-(tetrazolyl-1-yl)pyrrolidin-1-yl]methanone;

[0993] [(3S)-3-(Tetrazol-1-yl)pyrrolidin-1-yl]-[6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]methanone;

[0994] (3S)-1-[3-[4-(5-cyclobutyl-4H-1,2,4-triazol-3-yl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[0995] (3S)-1-[6-(3-cyclopropyl-1,2,4-triazol-1-yl)-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[0996] [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptane-2-yl]-[(3S)-3-(triazol-1-yl)pyrrolidin-1-yl]methanone;

[0997] [3-[6-(2-chlorophenoxy)-3-pyridinyl]azetidin-1-yl]-[(3R)-3-(triazol-1-yl)pyrrolidin-1-yl]methanone;

[0998] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3R)-3-(triazol-1-yl)pyrrolidin-1-yl]methanone;

[0999] [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptane-2-yl]-[(3R)-3-(triazol-1-yl)pyrrolidin-1-yl]methanone;

[1000] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3R)-3-(triazol-2-yl)pyrrolidin-1-yl]methanone;

[1001] [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptane-2-yl]-[(3R)-3-(triazol-2-yl)pyrrolidin-1-yl]methanone;

[1002] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methyl-methyl-amino]azetidin-1-yl]-[(3R)-3-(triazol-2-yl)pyrrolidin-1-yl]methanone;

[1003] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(triazol-1-yl)pyrrolidin-1-yl]methanone;

[1004] [7-[[6-(Difluoromethoxy)-3-pyridinyl]methyl]-2-azaspiro[3.5]nonan-2-yl]-[(3R)-3-(triazol-1-yl)pyrrolidin-1-yl]methanone;

[1005] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(triazol-2-yl)pyrrolidin-1-yl]methanone;

[1006] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[6-(triazol-2-yl)-2-azaspiro[3.3]heptan-2-yl]methanone;

[1007] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[6-(triazol-1-yl)-2-azaspiro[3.3]heptan-2-yl]methanone;

[1008] (3S)-1-[3-[4-(3-cyclopropyl-5-methyl-pyrazol-1-yl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[1009] (3S)-1-[3-[4-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[1010] (3S)-1-[7-(4-chloro-2-methylsulfonyl-phenyl)-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[1011] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1012] (3S)-1-[3-[4-(5-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[1013] (3S)-1-[3-[4-[5-[1-(trifluoromethyl)cyclopropyl]-4H-1,2,4-triazol-3-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[1014] (3S)-1-[6-[[5-(trifluoromethyl)pyrimidin-2-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[1015] [(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;

[1016] (3S)-1-[6-[[5-(trifluoromethoxy)-2-pyridinyl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[1017] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[5-(trifluoromethoxy)-2-pyridinyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[1018] rac-(3S)-1-[6-[[6-(trifluoromethyl)-3-pyridinyl]methyl]-2-azaspiro[3.4]octane-2-carbonyl]pyrrolidine-3-carboxamide;

[1019] [rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[6-(trifluoromethyl)-3-pyridinyl]methyl]-2-azaspiro[3.4]octan-2-yl]methanone;

[1020] (3S)-1-[7-(4-chloro-2-fluoro-phenyl)-2,7-diazaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[1021] (3S)-1-[7-(5-chloro-3-fluoro-2-pyridinyl)-2,7-diazaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[1022] 1-[4-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]-4-(trifluoromethyl)pyridin-2-one;

[1023] [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;

[1024] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[6-[(3R)-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridinyl]azetidin-1-yl]methanone;

[1025] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[6-[(3S)-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridinyl]azetidin-1-yl]methanone;

[1026] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[6-[3-(trifluoromethyl)azetidin-1-yl]-3-pyridinyl]azetidin-1-yl]methanone;

[1027] [(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;

[1028] [3-[4-(2-chloro-4-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1029] [3-[5-(4-chloro-2-methylsulfonyl-phenyl)-2-pyridinyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1030] [7-[(5-Fluoro-2-pyridinyl)methyl]-2-azaspiro[3.5]nonan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1031] [(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;

[1032] [7-[(5-chloro-2-pyridinyl)methyl]-2-azaspiro[3.5]nonan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1033] [(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;

[1034] [7-[[6-(Difluoromethoxy)-3-pyridinyl]methyl]-2-azaspiro[3.5]nonan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1035] [(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;

[1036] [(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;

[1037] [(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;

[1038] [6-[[3-Fluoro-5-(trifluoromethyl)-2-pyridinyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1039] [(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;

[1040] [(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;

[1041] [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;

[1042] [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;

[1043] [6-[[3-Fluoro-5-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptane-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1044] [(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;

[1045] [(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;

[1046] [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;

[1047] [(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;

[1048] [(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;

[1049] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[5-(trifluoromethyl)-3-pyridinyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[1050] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[4-(trifluoromethyl)-2-pyridinyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[1051] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[7-[[5-(trifluoromethyl)-2-pyridinyl]methyl]-2,7-diazaspiro[3.4]octan-2-yl]methanone;

[1052] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[3-[[1-(trifluoromethyl)cyclopropyl]methylamino]-1-bicyclo[1.1.1]pentyl]azetidin-1-yl]methanone;

[1053] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[3-[[[1-(trifluoromethyl)cyclopropyl]amino]methyl]-1-bicyclo[1.1.1]pentyl]azetidin-1-yl]methanone;

[1054] [3-[3-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-1-bicyclo[1.1.1]pentyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1055] [(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]pentyl]azetidin-1-yl]methanone;

[1056] (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;

[1057] (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;

[1058] [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;

[1059] [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;

[1060] [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;

[1061] (3S)-1-[6-[[3-Fluoro-5-(trifluoromethyl)-2-pyridinyl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[1062] (3S)-1-[7-[[5-(trifluoromethyl)-2-pyridinyl]methyl]-2,7-diazaspiro[3.4]octane-2-carbonyl]pyrrolidine-3-carboxamide;

[1063] (3S)-1-[3-[3-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-1-bicyclo[1.1.1]pentyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[1064] [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;

[1065] [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;

[1066] [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;

[1067] [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;

[1068] [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;

[1069] [(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;

[1070] [(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;

[1071] (3S)-1-[3-[3-[[1-(trifluoromethyl)cyclopropyl]methylamino]-1-bicyclo[1.1.1]pentyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[1072] (3S)-1-[3-[3-[[[1-(trifluoromethyl)cyclopropyl]amino]methyl]-1-bicyclo[1.1.1]pentyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[1073] rac-(1S,4R,5R)-2-[3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidine-1-carbonyl]-2-azabicyclo[2.1.1]hexane-5-carboxamide;

[1074] (3S)-1-[3-[3-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-1-bicyclo[1.1.1]pentyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[1075] (3S)-1-[7-(4-chloro-2-methylsulfonyl-phenyl)-2,7-diazaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide;

[1076] [6-[(5-methylsulfonyl-2-pyridinyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1077] [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;

[1078] [(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;

[1079] [(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;

[1080] [(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;

[1081] [(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]pentyl]azetidin-1-yl]methanone;

[1082] [(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;

[1083] [3-[4-(3,5-diisopropylpyrazol-1-yl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1084] [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;

[1085] [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[7-[[5-(trifluoromethyl)-2-pyridinyl]amino]-2-azaspiro[3.5]nonan-2-yl]methanone;

[1086] [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;

[1087] [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;

[1088] [3-[[2-Fluoro-4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidin-1-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[1089] [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[7-[[6-(trifluoromethyl)-3-pyridinyl]methyl]-2-azaspiro[3.5]nonan-2-yl]methanone;

[1090] [3-[6-(2-chlorophenoxy)-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[1091] [6-[(3,5-difluoro-2-pyridinyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[1092] [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;

[1093] [6-[2-Methylsulfonyl-4-(trifluoromethyl)phenyl]-2-azaspiro[3.3]heptane-2-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[1094] [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[[4-(trifluoromethylsulfonyl)phenyl]methoxy]azetidin-1-yl]methanone;

[1095] [6-(4-Methylsulfonylphenyl)-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[1096] [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[6-[4-(trifluoromethylsulfonyl)phenyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[1097] [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[4-[2-(trifluoromethyl)pyrimidin-5-yl]oxyphenyl]azetidin-1-yl]methanone;

[1098] [(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;

[1099] [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;

[1100] [3-[4-(3,5-dimethylpyrazol-1-yl)phenyl]azetidin-1-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[1101] [3-[6-(N-methylanilino)-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[1102] 2-Methoxy-4-[[2-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptane-6-yl]methyl]benzonitrile;

[1103] [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;

[1104] [3-[6-(4-fluorophenoxy)-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[1105] [3-(4-Cyclopropyl-2-fluoro-phenoxy)azetidin-1-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[1106] [3-(4-Chloro-3-cyclopropyl-phenoxy)azetidin-1-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[1107] [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;

[1108] [(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;

[1109] (3S)-1-[6-[[4-(Trifluoromethyl)pyrazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[1110] (3S)-1-[6-[[4-(Trifluoromethyl)imidazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[1111] (3S)-1-[6-[[3-(Trifluoromethyl)-1,2,4-triazol-1-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[1112] (3S)-1-[6-[[4-(Trifluoromethyl)oxazol-2-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[1113] (3S)-1-[6-[[3-(Trifluoromethyl)-1,2,4-thiadiazol-5-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[1114] (3S)-1-[6-[[4-(Trifluoromethyl)thiazol-2-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[1115] [6-[(5-fluoro-3-pyridinyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[1116] [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;

[1117] [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;

[1118] (3S)-1-[6-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[1119] [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;

[1120] [(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;

[1121] 3-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptane-6-yl]methyl]-5-(trifluoromethyl)benzonitrile;

[1122] 4-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptane-6-yl]methyl]-2-(trifluoromethyl)benzonitrile;

[1123] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[6-(trifluoromethoxy)-3-pyridinyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[1124] [(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;

[1125] [6-[(4-cyclopropylsulfonylphenyl)methyl]-2-azaspiro[3.3]heptane-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1126] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[3-[[6-(trifluoromethyl)-3-pyridinyl]methyl]-1-bicyclo[1.1.1]pentyl]azetidin-1-yl]methanone;

[1127] [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;

[1128] [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptane-2-yl]-[3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]methanone;

[1129] [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;

[1130] [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;

[1131] [6-[(3-chloro-5-fluoro-2-pyridinyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]methanone;

[1132] [3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]-[6-[[5-(trifluoromethoxy)-2-pyridinyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[1133] [6-[[3-Fluoro-5-(trifluoromethyl)-2-pyridinyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]methanone;

[1134] [3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]-[7-[[5-(trifluoromethyl)-2-pyridinyl]methyl]-2,7-diazaspiro[3.4]octan-2-yl]methanone;

[1135] [7-[(5-chloro-2-pyridinyl)methyl]-2-azaspiro[3.5]nonan-2-yl]-[3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]methanone;

[1136] [7-[[6-(Difluoromethoxy)-3-pyridinyl]methyl]-2-azaspiro[3.5]nonan-2-yl]-[3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]methanone;

[1137] [3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone;

[1138] [3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]-[3-[4-[3-(trifluoromethyl)azetidin-1-yl]phenyl]azetidin-1-yl]methanone;

[1139] [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]methanone;

[1140] [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;

[1141] [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;

[1142] (3S)-1-[3-[4-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[1143] [4-[(2-Chloro-4-methylsulfonyl-phenyl)methoxy]-1-piperidinyl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1144] (3S)-1-[4-[(2-chloro-4-methylsulfonyl-phenyl)methoxy]piperidine-1-carbonyl]pyrrolidine-3-carboxamide;

[1145] [4-[[4-Methylsulfonyl-3-(trifluoromethyl)phenoxy]methyl]-1-piperidinyl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1146] (3S)-1-[4-[[4-methylsulfonyl-3-(trifluoromethyl)phenoxy]methyl]piperidine-1-carbonyl]pyrrolidine-3-carboxamide;

[1147] [3-[3-(5-Cyclopropyl-3-methyl-pyrazol-1-yl)-1-bicyclo[1.1.1]pentyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1148] [3-[3-(3,5-dimethylpyrazol-1-yl)-1-bicyclo[1.1.1]pentyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1149] [4-[[2-Fluoro-4-(trifluoromethoxy)phenyl]methoxy]-1-piperidinyl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1150] [4-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-1-piperidinyl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1151] (3S)-1-[4-[[2-fluoro-4-(trifluoromethoxy)phenyl]methoxy]piperidine-1-carbonyl]pyrrolidine-3-carboxamide;

[1152] (3S)-1-[4-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]piperidine-1-carbonyl]pyrrolidine-3-carboxamide;

[1153] 5-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptane-6-yl]methyl]-2-(trifluoromethoxy)benzoic acid methyl ester;

[1154] [4-[[2-Methylsulfonyl-4-(trifluoromethyl)phenoxy]methyl]-1-piperidinyl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1155] [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;

[1156] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[5-(trifluoromethylsulfonyl)-2-pyridinyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[1157] [4-(5-chlorooxazolo[4,5-b]pyridin-2-yl)piperazin-1-yl]-[3-[[2-fluoro-4-(trifluoromethoxy)phenyl]methoxy]azetidin-1-yl]methanone;

[1158] 4-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptane-6-yl]methyl]benzenesulfonamide;

[1159] [(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;

[1160] [(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;

[1161] [(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;

[1162] [(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;

[1163] [(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;

[1164] [(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;

[1165] [(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;

[1166] [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;

[1167] [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;

[1168] [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;

[1169] [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;

[1170] [(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;

[1171] 4-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptane-6-yl]methyl]-2-(trifluoromethoxy)benzamide;

[1172] [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-2-pyridinyl]azetidin-1-yl]methanone;

[1173] [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[[6-(trifluoromethyl)-3-pyridinyl]methoxymethyl]azetidin-1-yl]methanone;

[1174] [3-[4-(1-methylsulfonylcyclopropyl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1175] [4-[(3-Chloro-5-methylsulfonyl-phenoxy)methyl]-1-piperidinyl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1176] 5-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptane-6-yl]methyl]-2-(trifluoromethoxy)benzamide;

[1177] [rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-(trifluoromethylsulfonimide)phenyl]azetidin-1-yl]methanone;

[1178] [(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]pentyl]azetidin-1-yl]methanone;

[1179] 4-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptane-6-yl]methyl]-2-(trifluoromethoxy)benzoic acid methyl ester;

[1180] [4-[[2-Methylsulfonyl-4-(trifluoromethoxy)phenoxy]methyl]-1-piperidinyl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[1181] [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[4-[[6-(trifluoromethyl)-3-pyridinyl]methoxymethyl]-1-piperidinyl]methanone;

[1182] [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[4-[[6-(trifluoromethyl)-3-pyridinyl]oxymethyl]-1-piperidinyl]methanone;

[1183] [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[4-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]-1-piperidinyl]methanone;

[1184] [4-[[4-Fluoro-3-(trifluoromethyl)phenoxy]methyl]-1-piperidinyl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[1185] [4-[[3-Fluoro-5-(trifluoromethyl)phenoxy]methyl]-1-piperidinyl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone;

[1186] [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;

[1187] [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[6-[[5-(trifluoromethylsulfonyl)-3-pyridinyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[1188] [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;

[1189] N'-[2-[3-[1-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]-1-bicyclo[1.1.1]pentyl]acetyl]cyclopropanecarboxyhydrazide;

[1190] [4-[[2-Methylsulfonyl-4-(trifluoromethoxy)phenyl]methoxy]-1-piperidinyl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1191] (3S)-1-[4-[[2-methylsulfonyl-4-(trifluoromethoxy)phenyl]methoxy]piperidine-1-carbonyl]pyrrolidine-3-carboxamide;

[1192] (3S)-1-[3-[3-(4-chloro-2-methylsulfonyl-phenyl)-1-bicyclo[1.1.1]pentyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[1193] 2-methoxy-4-[[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-4-piperidinyl]oxymethyl]benzonitrile;

[1194] (3S)-1-[2-(4-chloro-2-methylsulfonyl-phenyl)-6-azaspiro[3.4]octane-6-carbonyl]pyrrolidine-3-carboxamide;

[1195] 2-methoxy-4-[[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-4-piperidinyl]oxymethyl]benzamide;

[1196] (3S)-1-[3-[3-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-1-bicyclo[1.1.1]pentyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[1197] (3S)-1-[2-[(4-chloro-2-methylsulfonyl-phenyl)methyl]-6-azaspiro[3.4]octane-6-carbonyl]pyrrolidine-3-carboxamide;

[1198] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[3-(trifluoromethoxy)phenyl]sulfonyl-2-azaspiro[3.3]heptane-2-yl]methanone;

[1199] [(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;

[1200] [(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;

[1201] [3-[3-(4-Fluorophenyl)-1-bicyclo[1.1.1]pentyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1202] [3-[3-(4-methylsulfonylphenyl)-1-bicyclo[1.1.1]pentyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1203] [(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;

[1204] [(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;

[1205] [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;

[1206] [3-[[2-Fluoro-4-(trifluoromethylsulfonimide)phenyl]methoxy]azetidin-1-yl]-[rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1207] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[4-[[5-(trifluoromethyl)pyrazin-2-yl]amino]cuban-1-yl]methanone;

[1208] [(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;

[1209] [rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[3-(trifluoromethoxy)phenyl]sulfimidoyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[1210] [6-[[3-Fluoro-5-(trifluoromethylsulfonamidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1211] [rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[7-[[4-(trifluoromethyl)phenyl]sulfonimide]-2-azaspiro[3.5]nonan-2-yl]methanone;

[1212] [rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[7-[[3-(trifluoromethyl)phenyl]sulfonimide]-2-azaspiro[3.5]nonan-2-yl]methanone;

[1213] [3-[4-[2-(methylsulfonimidoyl)phenyl]phenyl]azetidin-1-yl]-[rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1214] [3-[(8R)-8-methyl-8-oxo-8λ6-thia-9-azatricyclo[8.4.0.02,7]tetradec-1(10),2(7),3,5,8,11,13-hepten-12-yl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1215] [3-[(8S)-8-methyl-8-oxo-8λ6-thia-9-azatricyclo[8.4.0.02,7]tetradec-1(10),2(7),3,5,8,11,13-hepten-12-yl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1216] [3-[3-(4-Fluoro-2-methylsulfonyl-phenyl)-1-bicyclo[1.1.1]pentyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1217] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[3-[3-(trifluoromethoxy)phenyl]-1-bicyclo[1.1.1]pentyl]azetidin-1-yl]methanone;

[1218] [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[4-[[5-(trifluoromethyl)-2-pyridinyl]methyl]piperazin-1-yl]methanone;

[1219] [4-[(2-methyloxazol-4-yl)methyl]piperazin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1220] [4-[(4-methylthiazol-5-yl)methyl]piperazin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1221] [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;

[1222] 4-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptane-6-yl]oxy]-2-(trifluoromethyl)benzonitrile;

[1223] 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]pentyl]benzonitrile;

[1224] [3-[3-(3-methyl-1H-pyrazol-5-yl)-1-bicyclo[1.1.1]pentyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1225] [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;

[1226] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[3-[4-(trifluoromethylsulfonyl)phenyl]-1-bicyclo[1.1.1]pentyl]azetidin-1-yl]methanone;

[1227] [3-[3-(4-chloro-2-methylsulfonyl-phenyl)-1-bicyclo[1.1.1]pentyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1228] [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;

[1229] 5-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptane-6-yl]oxy]-2-(trifluoromethyl)benzonitrile;

[1230] [6-[(5-fluoro-2-pyridinyl)oxy]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1231] [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;

[1232] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[[5-(trifluoromethyl)pyrazin-2-yl]amino]-1-bicyclo[1.1.1]pentyl]methanone;

[1233] (3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[4-(trifluoromethylsulfonimidoyl)phenoxy]-2-azaspiro[3.3]heptan-2-yl]methanone;

[1234] [(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[6-[[3-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[1235] [(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[6-[[3-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[1236] [(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[6-[[3-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[1237] 5-[[2-[(3S)-3-(1H-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptane-6-yl]methyl]-2-(trifluoromethyl)benzonitrile;

[1238] (3S)-1-[6-[[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[1239] (3S)-1-[6-[[1-methyl-5-(trifluoromethyl)pyrazol-4-yl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[1240] (3S)-1-[6-[[3-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[1241] (3S)-1-[6-[[4-Cyano-3-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[1242] (3S)-1-[6-[[6-(trifluoromethoxy)-3-pyridinyl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[1243] 5-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptane-6-yl]methyl]-2-(trifluoromethyl)benzonitrile;

[1244] [(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[6-[[4-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[1245] [(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[6-[[4-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[1246] rac-(3S)-1-[6-[[2-fluoro-4-(trifluoromethylsulfonimidoyl)phenyl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide;

[1247] [6-[[2-Fluoro-4-(trifluoromethylsulfonamidoyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[rac-(3S)-3-(1H-triazol-4-yl)pyrrolidin-1-yl]methanone;

[1248] [(3S)-3-(1H-triazol-4-yl)pyrrolidin-1-yl]-[6-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone;

[1249] [6-[[3-Fluoro-5-(trifluoromethylsulfonyl)phenyl]methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(1H-triazol-4-yl)pyrrolidin-1-yl]methanone;

[1250] [(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

[1251] [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.

[1252] In a preferred embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof, which is selected from:

[1253] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1254] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1255] 1-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[1256] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1257] (+)- 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;

[1258] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-imidazol-5-yl)pyrrolidin-1-yl]methanone;

[1259] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1260] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1261] [3-[[3-Chloro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1262] [3-[[2-Chloro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1263] (-)- or (+)-[3-[[2,4-bis(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone;

[1264] (+)- or (-)-1-[3-[4-(2,4-difluorophenyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide;

[1265] (+)- or (-)-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone;

[1266] (-)- or (+)-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidin-1-yl]methanone; and

[1267] 4-[1-[3-[4-[1-(Trifluoromethyl)cyclopropyl]phenyl]azetidine-1-carbonyl]pyrrolidin-3-yl]oxazolidin-2-one.

[1268] In a particular embodiment, the invention provides a pharmaceutically acceptable salt, especially a hydrochloride salt, of a compound of formula (I) as described herein. In another particular embodiment, the invention provides a compound of formula (I) as described herein as a free base.

[1269] In some embodiments, compounds of formula (I) are isotopically labeled by replacing one or more atoms with atoms having a different atomic mass or mass number. Such isotopically labeled (i.e., radiolabeled) compounds of formula (I) are considered to be within the scope of the present disclosure. Examples of isotopes that can be incorporated into compounds of formula (I) include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, and iodine, respectively, such as but not limited to 2 H. 3 H. 11 C. 13 C. 14 C. 13 N. 15 N. 15 O.17 O. 18 O. 31 P. 32 P. 35 S. 18 F. 36 Cl, 123 I and 125 I. Certain isotopically-labeled compounds of formula (I) (e.g., those containing a radioactive isotope) are useful in drug and / or substrate tissue distribution studies. 3 H) and carbon-14 (i.e. 14 C) are particularly useful for this purpose because they are easy to incorporate and detection means are readily available. For example, compounds of formula (I) may be enriched with 1, 2, 5, 10, 25, 50, 75, 90, 95 or 99% of a given isotope.

[1270] Using heavier isotopes such as deuterium (i.e. 2 H) substitutions may offer certain therapeutic advantages resulting from greater metabolic stability (eg, increased in vivo half-life or reduced dosage requirements).

[1271] Using positron-emitting isotopes such as 11 C. 18 F. 15 O and 13 N) substitution can be used to examine positron emission tomography (PET) studies of 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 using an appropriate isotopically labeled reagent in place of the non-labeled reagent previously used.

[1272] Preparation process

[1273] The preparation of the compound of formula (I) of the present invention can be carried out according to sequential or concurrent synthetic routes. The synthesis of the present invention is shown in the following general scheme. The skills required for performing the reaction and purifying the resulting product are known to those skilled in the art. Unless otherwise indicated, the substituents and indices used in the following method descriptions have the meanings provided herein.

[1274] If one of the starting materials, intermediates or compounds of formula (I) contains one or more functional groups that are unstable or reactive under the reaction conditions of one or more reaction steps, appropriate protecting groups may be introduced before applying key steps of methods well known in the art (such as "Protective Groups in Organic Chemistry" by TW Greene and PGM Wutts, 5th edition, 2014, John Wiley & Sons, NY). Such protecting groups may be removed at a later stage of the synthesis using standard methods described in the literature.

[1275] If the starting material or intermediate contains a stereogenic center, the compound of formula (I) can be obtained in the form of a mixture of diastereomers or enantiomers, which can be separated by methods well known in the art (e.g., chiral HPLC, chiral SFC or chiral crystallization). Racemic compounds can be separated into corresponding enantiomers, for example, by diastereomeric salts, which are crystallized with optically pure acids, or by specific chromatography separations of enantiomers using chiral adsorbents or chiral eluents. Starting materials and intermediates containing stereogenic centers can also be separated to provide starting materials and intermediates enriched in diastereomers / enantiomers. Using such diastereomer / enantiomer-enriched starting materials and intermediates in the synthesis of compounds of formula (I) will generally produce diastereomers / enantiomer-enriched compounds of the corresponding formula (I).

[1276] Those skilled in the art will recognize that in the synthesis of compounds of formula (I) (if not desired), an "orthogonal protecting group strategy" will be applied, which allows multiple protecting groups to be cleaved each time without affecting other protecting groups in the molecule. The principle of orthogonal protection is well known in the art and has also been reported in the literature (e.g., Barany and RB Merrifield, J. Am. Chem. Soc. 1977, 99, 7363; H. Waldmann et al., Angew. Chem. Int. Ed. Engl. 1996, 35, 2056).

[1277] Those skilled in the art will recognize that the order of reactions may vary depending on the reactivity and nature of the intermediates.

[1278] In more detail, the compound of formula (I) can be manufactured by the method given below, by the method given in the examples or by similar methods. The appropriate reaction conditions for each reaction step are known to those skilled in the art. Similarly, the reaction conditions affecting the reaction reported in the relevant literature are described, for example: Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 2nd Edition, Richard C. Larock. John Wiley & Sons, New York, NY. 1999. It is convenient to react in the presence or absence of a solvent. There are no particular restrictions on the nature of the solvent used, as long as it has no adverse effect on the reaction or the reagents involved and can dissolve the reagents at least to a certain extent. The described reaction can occur over a wide temperature range, and the precise reaction temperature is not critical to the present invention. The above reaction can be conveniently performed in a temperature range of -78°C to reflux. The time required for the reaction can also vary over a wide range, depending on many factors, particularly the reaction temperature and the nature of the reagents. However, it usually takes 0.5 hours to several days to obtain the intermediates and compounds. The reaction sequence is not limited to the one shown in the schemes, but, depending on the starting materials and their respective reactivity, the order of the reaction steps can be freely varied.

[1279] If starting materials or intermediates were not commercially available or their synthesis was not reported in the literature, they could be prepared by analogy to existing preparations of close analogs or as outlined in the experimental section.

[1280] The following abbreviations are used in this text:

[1281] AcOH = acetic acid, ACN = acetonitrile, Bn = benzyl, Boc = tert-butyloxycarbonyl, CAS RN = Chemical Abstracts Registry Number, Cbz = benzyloxycarbonyl, CPME = cyclopentyl methyl ether, Cs 2 CO 3= cesium carbonate, CO = carbon monoxide, CuCl = cuprous chloride (I), CuCN = cuprous cyanide (I), CuI = cuprous iodide (I), 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 = dimethoxybenzylamine = 1,2-dimethylethane, DMEDA = N,N'-dimethyl-1,2-ethylenediamine, DMF = N,N-dimethylformamide, DIPEA = N,N-diisopropylethylamine, dppf = 1,1-bis(diphenylphosphino)ferrocene, EDC.HCl = N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride, EI = electron impact, ESI = electrospray ionization, EtOAc = ethyl acetate, EtOH = ethanol, h = hour, FA = formic acid, H 2 O=water, H 2 SO 4 = sulfuric acid, HATU = 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate, HBTU = O-benzotriazole-N,N,N',N'-tetramethyl-uronium-hexafluoro-phosphate, HCl = hydrogen chloride, HOBt = 1-hydroxy-1H-benzotriazole; HPLC = high performance liquid chromatography, iPrMgCl = isopropylmagnesium chloride, I 2 = iodine, IPA = 2-propanol, ISP = ion spray positive (mode), ISN = ion spray negative (mode), K 2 CO 3 = Potassium carbonate, KHCO 3 = Potassium bicarbonate, KI = Potassium iodide, KOtBu = Potassium tert-butoxide, KOH = Potassium hydroxide, K 3 PO 4 = Tripotassium phosphate, LiAlH 4 or LAH = lithium aluminum hydride, LiHMDS = lithium bis(trimethylsilyl)amide, LiOH = lithium hydroxide, mCPBA = meta-chloroperbenzoic acid, MgSO 4 = magnesium sulfate, min = minute, mL = milliliter, MPLC = medium pressure liquid chromatography, MS = mass spectrometry, MTBE = methyl tert-butyl ether, nBuLi = n-butyl lithium, NaBH 3 CN = sodium cyanoborohydride, NaH = sodium hydride, NaHCO 3 =Sodium bicarbonate, NaNO 2 =Sodium nitrite, NaBH(OAc) 3 = sodium triacetoxyborohydride, NaOH = sodium hydroxide, Na 2 CO 3=Sodium carbonate, Na 2 SO 4 =Sodium sulfate, Na 2 S 2 O 3 = sodium thiosulfate, NBS = N-bromosuccinimide, nBuLi = n-butyllithium, NEt 3 = triethylamine (TEA), NH 4 Cl = ammonium chloride, NMP = N-methyl-2-pyrrolidone, OAc = acetoxy, T 3 P = propylphosphonic anhydride, PE = petroleum ether, PG = protecting group, Pd-C = palladium on activated carbon, PdCl 2 (dppf)-DCM = 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) chloride DCM complex, Pd 2 (dba) 3 =Tris(dibenzylideneacetone)dipalladium(0), Pd(OAc) 2 = Palladium(II) acetate, Pd(OH) 2 = Palladium hydroxide, Pd(PPh 3 ) 4 = tetrakis(triphenylphosphine)palladium(0), 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 = methyl tert-butyl ether, TEA = triethylamine, TFA = trifluoroacetic acid, THF = tetrahydrofuran, TMEDA = N,N,N',N'-tetramethylethylenediamine, ZnCl 2 =zinc chloride, Hal = halogen.

[1282] Among them, A, B, L, R 1 , R 2 , R 3 , R 4 , p and q as described herein can be prepared analogously to literature procedures and / or as for example Solution 1 Synthesized as described in.

[1283]

[1284] Solution 1

[1285] Thus, compound 1 is reacted with intermediate 2 in the presence of a urea forming agent such as bis(trichloromethyl)carbonate using a suitable base and solvent such as sodium bicarbonate in DCM to afford a compound of formula IA ( Step a). Further, urea forming agents include, but are not limited to, phosgene, trichloromethyl chloroformate, (4-nitrophenyl) carbonate, 1,1'-carbonyl-bis-(1,2,4-triazole) or 1,1'-carbonyldiimidazole. Such reactions and the use of these reagents are 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 adding reagents may be important in such reactions due to the reactivity and stability of the intermediate formed carbamoyl chloride and to avoid the formation of undesirable symmetrical urea by-products by the following means.

[1286] The compounds of formula IA can be obtained in the form of diastereomers or mixtures of enantiomers, which can be separated by methods well known in the art (e.g., chiral HPLC, chiral SFC or chiral crystallization). Racemic compounds can be separated into the corresponding enantiomers, for example, via diastereomeric salts, by crystallization with optically pure acids, or by specific chromatography using chiral adsorbents or chiral eluents to separate the enantiomers.

[1287] In R 4 In the case of a 5-membered heteroaromatic system containing a nitrogen atom that can be alkylated, compound IA can be alkylated using a base such as Na 2 CO 3 , K 2 CO 3 , NaH or KotBu) in a suitable solvent such as THF or DMF with a suitable alkylating agent such as iodomethane to give compound IA.

[1288] Among them, A, B, L, R 1 , R 2 , R 3 , R 4 , p and q as described herein can be prepared analogously to literature procedures and / or as for example Solution 2 Synthesized as described in.

[1289]

[1290] Solution 2

[1291] Thus, intermediate 2 can be coupled with an activated form of carboxylic acid 3a (G=OH) or alternatively with a carboxylic acid chloride 3b (G=Cl) to provide compound IB ( Step a). This type of amide coupling with carboxylic acids is widely described in the literature and can be accomplished by using coupling reagents such as CDI, DCC, HATU, HBTU, HOBT, TBTU, T3P or Mukaiyama reagent (Mukaiyama T. Angew. Chem., Int. Ed. Engl. 1979, 18, 707) in a suitable solvent (e.g. DMF, DMA, DCM or dioxane), optionally in the presence of a base (e.g. TEA, DIPEA (Huenig's base) or DMAP). Alternatively, the carboxylic acid 3a can be converted to its acid chloride 3b by treatment with, for example, thionyl chloride or oxalyl chloride, neat or optionally in a solvent (e.g. 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, Huenig'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 affords compound IB ( Step a ).

[1292] The compounds of formula IB can be obtained in the form of diastereomers or mixtures of enantiomers, which can be separated by methods well known in the art (e.g., chiral HPLC, chiral SFC or chiral crystallization). Racemic compounds can be separated into the corresponding enantiomers, for example, via diastereomeric salts, by crystallization with optically pure acids, or by specific chromatography using chiral adsorbents or chiral eluents to separate the enantiomers.

[1293] In R 4 In the case of a 5-membered heteroaromatic system containing a nitrogen atom that can be alkylated, compound IB is alkylated with a base such as Na 2 CO 3 , K 2 CO 3 , NaH or KotBu) with a suitable alkylating agent (such as iodomethane) to give compound IB.

[1294] Among them, A, B, R 1 , R 2 , R 3 , R 4 , p and q as described herein can be prepared analogously to literature procedures and / or as for example Solution 3 Synthesized as described in.

[1295]

[1296] Solution 3

[1297] Thus, intermediate 4 (commercially available or prepared by methods known in the art, wherein X is bromine or iodine) can be subjected to a cross-coupling reaction (such as a Suzuki, Buchwald-Hartwig, Negishi, Heck, Stille or Sonogashira coupling reaction) with intermediate 5 (commercially available or prepared by methods known in the art).

[1298] For example, intermediate 4 can be reacted with intermediate 5 (wherein FG represents an aryl or heteroaryl boronic acid (FG = B (OH) 2) or a boronic ester (FG = for example 4,4,5,5-tetramethyl-2-phenyl-1,3,2-dioxaborolane (pinacol) ester)) (commercially available or used, for example, in Dennis G. Hall (ed.) "Boronic Acids-Preparation and Applications in Organic Synthesis and Medicine", 1st edition, 2005, John Wiley & Sons, New York) using 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 a mixture 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 to give compound IC (step a). Suzuki reactions of this type are 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 are familiar to those skilled in the art. Alternatively, aryl- or heteroaryl-trifluoroborate 19c (FG═BF3) can be used in a cross-coupling reaction using 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 the presence of a suitable base such as cesium carbonate or potassium phosphate in a solvent such as toluene, THF, dioxane, water or a mixture thereof at a temperature between room temperature and the boiling point of the solvent or solvent mixture (step a).

[1299] For example, intermediate 4 can be reacted with intermediate 5 (where FG is Sn(alkyl) 3 and the alkyl group is preferably n-butyl or methyl) using a suitable catalyst and solvent (such as, for example, tetrakis(triphenylphosphine)-palladium(0) in DMF) at a temperature between room temperature and the boiling point of the solvent or solvent mixture to provide intermediate 10 ( Step a ). Stille reactions of this type are well known in the art and are described in the literature, for example, Org. React. 1997, 50, 1-652, ACS Cata l. 2015, 5, 3040-3053.

[1300] For example, intermediate 4 can be reacted with intermediate 5 (wherein FG is ZnHal and Hal is preferably bromine or iodine, which can be obtained commercially or prepared by literature methods) using an appropriate catalyst and solvent system (such as, for example, [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 provide intermediate 10 ( Step a ). This type of Negishi reaction is well known in the art and is also described in the literature, for example Org. Lett., 2005, 7, 4871, ACS Catal. 2016, 6, 1540–1552. Acc. Chem. Res. 1982, 15, pp. 340-348. Alternatively, intermediate 10 can be prepared by applying a literature method: first, intermediate 8 (wherein X is, for example, iodine) is converted into the corresponding zinc substance (for example, 8 is reacted with Zn powder in the presence of chlorotrimethylsilane and 1,2-dibromoethane in a suitable solvent such as DMA), and the zinc substance is subsequently coupled with an aryl- or heteroaryl bromide or iodide under the aforementioned conditions.

[1301] Alternatively, intermediate 4 (where X is preferably bromine) can be cross-electrophilically coupled with aryl or heteroaryl bromide 5 (where FG represents bromine) under 420 nm blue light illumination using an appropriate photocatalyst (such as [Ir{dF(CF 3 )ppy} 2 (dtbpy)]PF 6 ([4,4'-bis(1,1-dimethylethyl)-2,2'-bipyridyl-N1,N1']bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl-N]phenyl-C]iridium(III) hexafluorophosphate)), nickel catalysts (such as NiCl 2glyme (dichloro(dimethoxyethane)nickel), 4,4'-di-tert-butyl-2,2'-bipyridyl and tris(trimethylsilyl)silane) in the presence of a suitable base such as anhydrous sodium carbonate in a solvent such as DME. This type of reaction is described in the literature, for example, J.Am.Chem.Soc.2016,138,8084 ( Step a ).

[1302] Alternatively, intermediate 4 (wherein X is iodine, bromine, chlorine or OTf) can be reacted with intermediate 5 (wherein FG represents a functional group such as RC=CH or RC≡CH) using one of the cross-coupling methods described previously to provide compound IC ( Step a ).

[1303] Compounds of formula IC can be obtained in the form of diastereomers or mixtures of enantiomers, which can be separated by methods well known in the art (e.g., chiral HPLC, chiral SFC or chiral crystallization). Racemic compounds can be separated into the corresponding enantiomers, for example, by diastereomeric salts, by crystallization with optically pure acids, or by specific chromatography using chiral adsorbents or chiral eluents to separate the enantiomers.

[1304] In R 4 In the case of a 5-membered heteroaromatic system containing a nitrogen atom that can be alkylated, compound IC is alkylated with a base such as Na 2 CO 3 , K 2 CO 3 , NaH or KotBu) with a suitable alkylating agent (such as iodomethane) to give compound IC.

[1305] In some embodiments, Intermediate 1 is an intermediate of type 1a. 1 , R 2 , R 3 , A and B as described herein) can be obtained by methods known in the art and as Solution 4 The preparations were exemplified by the general synthetic procedures outlined in .

[1306]

[1307] Solution 4

[1308] Intermediate 2a (commercially available or prepared by methods known in the art, wherein PG represents a suitable protecting group and X is bromine or iodine) is reacted with compound 8a (commercially available or prepared by methods known in the art, wherein FG represents a suitable functional group (such as, for example, chlorine, bromine, iodine, -OSO 2Alkyl (e.g. mesylate (methylsulfonic acid)), –OSO 2 Fluoroalkyl (e.g. triflate (trifluoromethanesulfonic acid)) or –OSO 2 A cross-coupling reaction (such as Negishi, Heck, Stille, Suzuki, Sonogashira or Buchwald-Hartwig coupling reaction) is performed with an aromatic group (e.g. tosylate (p-toluenesulfonic acid)). Reactions of this type are widely described in the literature and are well known to those skilled in the art ( Step a ).

[1309] For example, intermediate 2a (wherein X is preferably bromine or iodine) can be reacted with intermediate 8a (wherein FG represents a functional group such as boronic acid (FG = B(OH) 2 ) or a boric acid ester (FG = e.g. 4,4,5,5-tetramethyl-2-phenyl-1,3,2-dioxaborolane (pinacol) ester)) (commercially available or prepared using literature procedures such as described in Dennis G. Hall (ed.) "Boronic Acids - Preparation and Applications in Organic Synthesis and Medicine", 1st edition, 2005, John Wiley & Sons, New York) using 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. Na 2 CO 3 、NaHCO 3 , KF, K 2 CO 3 or TEA) at a temperature between room temperature and the boiling point of the solvent or solvent mixture to obtain intermediate 4a ( Step a This type of Suzuki reaction is 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 (wherein FG represents a functional group such as trifluoroborate (FG = BF3 )) can be used in cross-coupling reactions (using 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 the presence of a suitable base (such as cesium carbonate or potassium phosphate), in a solvent (such as toluene, THF, dioxane, water or a mixture thereof), at a temperature between room temperature and the boiling point of the solvent or solvent mixture) ( Step a ).

[1310] Alternatively, intermediate 2a can be reacted with intermediate 8a (wherein FG represents a functional group, such as stannane, where FG is Sn(alkyl) 3 and the alkyl group is preferably n-butyl or methyl) using a suitable catalyst and solvent (such as, for example, tetrakis(triphenylphosphine)-palladium(0) in DMF) at a temperature between room temperature and the boiling point of the solvent or solvent mixture to provide intermediate 4a ( Step a ). Stille reactions of this type are well known in the art and are described in the literature, for example Org. React. 1997, 50, 1-652, ACS Catal. 2015, 5, 3040-3053.

[1311] In addition, intermediate 2a can be reacted with intermediate 8a (wherein FG represents a functional group, such as zinc halide (FG = ZnHal and Hal, preferably Br or I), which can be obtained commercially or prepared by literature methods) using an appropriate catalyst and solvent system (such as, for example, [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 provide intermediate 4a ( step a ). This type of Negishi reaction is well known in the art and is also described in the literature, for example Org. Lett., 2005, 7, 4871, ACS Catal. 2016, 6, 1540–1552. Acc. Chem. Res. 1982, 15, pp. 340-348. Alternatively, intermediate 10 can be prepared by first converting intermediate 2a (wherein X is, for example, iodine) into the corresponding zinc species (for example, 2a with Zn powder in the presence of chlorotrimethylsilane and 1,2-dibromoethane in a suitable solvent such as DMA) using a literature method, and subsequently coupling the zinc species with an aryl- or heteroaryl-bromide or iodide under the aforementioned conditions.

[1312] Alternatively, intermediate 2a (wherein X is preferably bromine) can be cross-electrophilicly coupled with intermediate 8a (wherein FG represents a functional group such as bromine (FG=Br)) under 420 nm blue light illumination using an appropriate photocatalyst (such as [Ir{dF(CF 3 )ppy} 2 (dtbpy)]PF 6 ([4,4'-bis(1,1-dimethylethyl)-2,2'-bipyridyl-N1,N1']bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl-N]phenyl-C]iridium(III) hexafluorophosphate)), nickel catalysts (such as NiCl 2 glyme (dichloro(dimethoxyethane)nickel), 4,4'-di-tert-butyl-2,2'-bipyridyl and tris(trimethylsilyl)silane) in the presence of a suitable base such as anhydrous sodium carbonate in a solvent such as DME. This type of reaction is described in the literature, for example, J.Am.Chem.Soc.2016,138,8084 ( Step a ).

[1313] Alternatively, intermediate 2a (wherein X is preferably iodine) can be reacted with arylboronic acid 8a (FG=B(OH) 2 ) Suzuki-Miyaura cross-coupling reaction using a suitable nickel catalyst (such as nickel (II) iodide) in the presence of racemic-(1R, 2R)-2-aminocyclohexane-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, optionally using microwave heating, to give intermediate 4a. This type of reaction is described in the literature, for example, Chemistry Select. 2017, 2, 8841 ( Step a ).

[1314] Alternatively, intermediate 2a can be reacted with intermediate 8a (wherein FG represents a functional group such as an amine) using a suitable catalyst and solvent (such as, for example, tris(dibenzylideneacetone)dipalladium(0)chloroform adduct and X-Phos or bis(diphenylphosphino)-1,1'-binaphthalene and palladium(II) acetate in tert-butyl alcohol or 1,4-dioxane) and a suitable base (such as Cs2CO3 or KOtBu) at a temperature between room temperature and the boiling point of the solvent or solvent mixture to provide intermediate 4a ( Step a ). Buchwald-Hartwig reactions of this type are well known in the art and are described in the literature, for example Angewandte Chemie. 2019, 58, 17118-17129.

[1315] For example, intermediate 2a (wherein X is preferably bromine or iodine) can be reacted with intermediate 5a (wherein FG represents a functional group such as 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) and X = F) (commercially available or prepared using literature procedures such as described in Dennis G. Hall (ed.) "Boronic Acids - Preparation and Applications in Organic Synthesis and Medicine", 1st edition, 2005, John Wiley & Sons, New York) using 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 an appropriate solvent (e.g. dioxane, dimethoxyethane, water, toluene, DMF or mixtures thereof) and a suitable base (e.g. Na 2 CO 3 、NaHCO 3 , KF, K 2 CO 3 or TEA) at a temperature between room temperature and the boiling point of the solvent or solvent mixture to obtain intermediate 6a ( Step c This type of Suzuki reaction is 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.

[1316] Intermediate 6a can be reacted with intermediate 7a (where FG = S) under nucleophilic substitution conditions in a suitable solvent (such as DMSO) at a temperature between 0°C and 100°C. - Na + and R2 = Me) to give compound 4a (step d).

[1317] Alternatively, the intermediate of 4a obtained in this manner 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.

[1318] Removal of protecting groups from intermediate 4a (wherein PG represents a protecting group such as tert-butoxycarbonyl (BOC)) can be performed using methods well known in the art and as described in the literature (see TW Greene and PGM Wutts, "Protective Groups in Organic Chemistry", 5th edition, 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 provide intermediate 1a (step b).

[1319] In some embodiments, Intermediate 1 is an intermediate of type 1b. Intermediate 1b (wherein R 1 , R 2 , R 3 , R 4 , A and B as described herein) can be obtained by Solution 5 The preparations were carried out using a variety of conditions exemplified in the general synthetic procedures outlined in .

[1320]

[1321] Solution 5

[1322] An organometallic compound of the type 3b (wherein MX is, for example, Li or MgCl, MgBr or MgI) is added to intermediate 4b (wherein PG is a suitable protecting group, for example, a Boc group) to provide intermediate 5b ( Step a ). Reactions of this type are well known in the art and 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). In the case where compounds 3b (wherein MX = MgHal, where Hal is Cl, Br or I (Grignard reagent)) are not commercially available, they can be prepared, for example, by reacting the corresponding aryl or heteroaryl halide 2b with magnesium in a suitable solvent such as THF, optionally in the presence of a catalytic amount of iodine at a temperature ranging from 0°C to the boiling point of the solvent ( Step d). Alternatively, 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) can be used to carry out a lithium halogen exchange reaction with an aryl or heteroaryl halide 2b at a temperature range between -20°C and -78°C (preferably at -78°C) to generate the corresponding lithiated aryl or lithiated heteroaryl intermediate (M=Li). The in situ prepared lithiated aryl or heteroaryl intermediate is nucleophilically added to a ketone of type 4b (wherein PG is a suitable protecting group such as a Boc group) in a solvent such as THF and preferably at a temperature of -78°C to afford the corresponding tertiary alcohol 5b ( Step a ).

[1323] Subsequent elimination of the tertiary hydroxyl group in intermediate 5b using acidic conditions such as 4M HCl in dioxane in a solvent such as MeOH, or preferably TFA in DCM, optionally accompanied by removal of an acid labile protecting group such as a Boc protecting group, affords the corresponding olefin intermediate 6b ( Step b ).

[1324] The reaction is carried out using a catalyst such as Pd(OH) in a solvent such as THF, MeOH, EtOH, EtOAc or mixtures thereof, preferably Pd / C in THF, under atmospheric pressure such as hydrogen. 2 or Pd / C) to give the intermediate type 1b ( Step c ).

[1325] Intermediate 4b is commercially available and / or can be prepared in analogy to the methods described in the following literature, for example Bioorg. Med. Chem. Lett. 2011, 21 (18), 5191, WO 2012 / 155199, WO 2016 / 180536, Bioorg. Med. Chem. Lett. 2008, 18 (18), 5087, WO 2007 / 117557, J. Am. Chem. Soc. 2017, 139 (33), 11353, J. Med. Chem. 2017, 60 (13), 5507.

[1326] In some embodiments, Intermediate 1 is an intermediate of type 1c. Intermediate 1c (wherein R 1 , R 2 , R 3 , A and B as described herein) can be obtained by methods well known in the art and as Solution 6 The preparations were exemplified by the general synthetic procedures outlined in .

[1327]

[1328] Solution 6

[1329] Ketone 2c, which is commercially available or prepared by methods known in the art, wherein PG is a suitable protecting group, can be subjected to a Wittig reaction with an alkylidene triphenylphosphane of type 3c, for example in a suitable solvent such as THF, methyl-THF or DMSO, to give intermediate 5c ( Step a ). Phosphine 3c can be formed by treating the corresponding phosphonium salt 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. Phosphonium salts are easily obtained from aryl / heteroaryl / heterocyclic substituted alkyl halides (wherein the halide is Cl, Br and iodine) and triphenylphosphine in a suitable solvent such as toluene. Heating can be applied to accelerate the reaction or drive the reaction to completion (e.g., HJ Cristau, F. Plénat in PATAI'S Chemistry of Functional Groups, editor: Frank R. Hartley, August 2006, series editor: Prof. Saul Patai).

[1330] Alternatively, intermediate 5c can be obtained using a Horner-Wadsworth-Emmons (HWE) reaction using ketone 2c and phosphonate 4c, where R a is an alkyl group, such as methyl or ethyl. Phosphonate 4c is α-metallated in situ using a suitable base and solvent, such as NaH, nBuLi or KOtBu( Step a Phosphonates 4c are readily prepared by alkylation of aryl / heteroaryl / heterocyclic halides (wherein the halides are Cl, Br and iodine) with commercially available trialkyl phosphites using, for example, the Arbuzov reaction (eg, Chem. Rev. 1984, 84, 577).

[1331] Both types of olefination reactions are extensively described in the literature (eg Current Org. Chem. 2015, 19(9), p. 744; Chem. Rev. 1989, 89(4), 863; Org. React. 1977, 25, 73; Liebigs Ann. / Recueil 1997, 1283; Acc. Chem. Res. 1983, 16, 411).

[1332] The double bond in intermediate 5c is reduced using, for example, hydrogen in the presence of a suitable catalyst such as palladium on carbon in an appropriate solvent or solvent mixture such as EtOAc, MeOH or AcOH to give compound 6c ( Step b ).

[1333] The protecting groups in intermediate 6c are removed using methods known in the art (e.g., removal of the Boc group using TFA in DCM or 4M HCl in dioxane at temperatures between 0°C and room temperature; removal of the Boc group using a suitable catalyst such as Pd or Pd(OH) supported on activated carbon in a suitable solvent such as MeOH, EtOH, EtOAc or mixtures thereof). 2 In the case of using hydrogen to remove the Cbz group; and as described in: "Protective Groups in Organic Chemistry", from TW Greene and PGM Wuts, 4th edition, 2006, Wiley NY), to provide intermediate 1c ( Step c ).

[1334] In some embodiments, intermediate 1 is an intermediate of type 1d. Intermediate 1d (wherein R 1 , R 2 , R 3 , A and B as described herein) can be obtained by methods well known in the art and as Solution 7 The preparations were exemplified by the general synthetic procedures outlined in .

[1335]

[1336] Solution 7

[1337] Alcohols of type 2d can be reacted with intermediate 3d by Mitsunobu reaction, where PG is a suitable protecting group such as Cbz, Boc or Bn, using an appropriate phosphine such as triphenylphosphine and a dialkylazodicarboxylate such as DEAD or DIAD in a suitable solvent such as THF to give intermediate 4d ( Step a That type of Mitsunobu reaction is widely described in the literature (eg, Org. Chem. Front. 2015, 2, 739; Chem. Rev. 2009, 109(6), 2551).

[1338] Alternatively, intermediate 4d can be prepared from alcohol 2d, which can be alkylated with compound 5d, where LG is a suitable leaving group such as chloro, bromo, iodo, OSO 2 Alkyl (e.g., methanesulfonic acid), OSO 2 Fluoroalkyl (e.g., trifluoromethanesulfonic acid) or OSO 2Aryl (e.g., p-toluenesulfonic acid), the alkylation is carried out using a suitable base such as NaH or Cs2CO3 in a suitable solvent (e.g., DMF or ACN) at a temperature between 0°C and the boiling temperature of the solvent ( Step c ).

[1339] In addition, intermediate 4d can be alkylated with 3d-type alcohols and compound 6d in Step c The synthesis conditions are as follows ( Step d ).

[1340] Apply literature methods and e.g. Solution 4 Step b The method described removes the protecting group in intermediate 4d to provide intermediate 1d ( Step b ).

[1341] In some embodiments, intermediate 1 is an intermediate of type 1e. Intermediate 1e (wherein R 1 , R 2 , R 3 , A and B as described herein) can be obtained by Solution 8 The preparations were carried out using a variety of conditions exemplified in the general synthetic procedures outlined in .

[1342]

[1343] Solution 8

[1344] Alcohols of type 2d can be reacted with intermediate 3e by Mitsunobu reaction, wherein PG is a suitable protecting group, such as Cbz, Boc or Bn, using an appropriate phosphine (such as triphenylphosphine) and a dialkylazodicarboxylate (such as DEAD or DIAD) in a suitable solvent (such as THF, DCM or ACN) to give intermediate 2e ( Step a That type of Mitsunobu reaction is widely described in the literature (eg, Org. Chem. Front. 2015, 2, 739; Chem. Rev. 2009, 109(6), 2551).

[1345] Apply literature methods and e.g. Solution 4 Step b The method described removes the protecting group in intermediate 2e to provide intermediate 1e ( Step b ).

[1346] Alternatively, intermediate 2e can be prepared from alcohol 2d, which can be alkylated with compound 4e, where LG is a suitable leaving group such as chloro, bromo, iodo, OSO 2 Alkyl (e.g., methanesulfonic acid), OSO 2 Fluoroalkyl (e.g., trifluoromethanesulfonic acid) or OSO 2Aryl (e.g., p-toluenesulfonic acid), the alkylation is carried out using a suitable base such as Cs 2 CO 3 , Huenig's base or NaH in a suitable solvent such as DMF at a temperature between 0°C and the boiling temperature of the solvent ( Step c ).

[1347] In some embodiments, intermediate 1 is an intermediate of type 1f. Intermediate 1f (wherein R 1 , R 2 , R 3 , A and B as described herein) can be obtained by methods known in the art and as Solution 9 The preparations were exemplified by the general synthetic procedures outlined in .

[1348]

[1349] Solution 9

[1350] Intermediate 3f can be prepared from alcohol 3d (commercially available or by methods known to those skilled in the art, and wherein PG is a suitable protecting group such as Cbz, Boc or Bn) by reacting with compound 2f (wherein LG is a suitable leaving group such as chloro, bromo, iodo, OSO 2 Alkyl (e.g. methanesulfonic acid), OSO 2 Fluoroalkyl (e.g. trifluoromethanesulfonic acid) or OSO 2 The alkylation of the aryl group (e.g. p-toluenesulfonic acid) using a suitable base (such as sodium hydride, Huenig's base or potassium tert-butoxide) in a suitable solvent (e.g. in DMF or THF) at a temperature between 0°C and the boiling temperature of the solvent ( step step a ).

[1351] The protecting groups in intermediate 3f are removed using methods known in the art (e.g., removal of the Boc group using TFA in DCM at temperatures between 0°C and room temperature; removal of the Boc group using a suitable catalyst such as Pd or Pd(OH) supported on activated carbon in a suitable solvent such as MeOH, EtOH, EtOAc or mixtures thereof). 2 In the case of using hydrogen to remove the Cbz group; and as described, for example, in the following literature: "Protective Groups in Organic Chemistry", from TW Greene and PGM Wuts, 4th edition, 2006, Wiley NY), to provide intermediate 1f ( Step b ).

[1352] In some embodiments, intermediate 1 is a 1g-type intermediate. 1 , R 2 , R 3 , A and B as described herein) can be obtained by methods well known to those skilled in the art and as Solution 9 The preparations were exemplified by the general synthetic procedures outlined in .

[1353]

[1354] Solution 9

[1355] Aldehydes 2g, which are commercially available or prepared by methods known in the art, can be prepared using alkylidene triphenylphosphanes of type 3c and phosphonates of type 4c, respectively, using, for example Solution 6 Step a The conditions described above were used for Wittig reaction or Horner-Wadsworth-Emmons (HWE) reaction to obtain intermediate 3g ( Step a ).

[1356] Apply the literature conditions or Solution 5 Step c or Solution 6 Step b The double bond in intermediate 3g is reduced under the conditions described above to obtain compound 4g ( Step b ).

[1357] Using methods known in the art and such Solution 4 Step b Removal of the protecting group from intermediate 4g provides intermediate 1g ( Step c ).

[1358] In another embodiment, intermediate 1 is a 1h-type intermediate. 1 , R 2 , R 3 , A and B as described herein) can be obtained by methods well known in the art and as Solution 10 The preparations exemplified by the general synthetic procedures described in .

[1359]

[1360] Solution 10

[1361] Alkyne 2h (commercially available or prepared by methods known in the art, and wherein PG represents a suitable protecting group such as, for example, a Boc, Cbz or Bn protecting group) can be subjected to a Sonogashira reaction (e.g., Chem. Soc. Rev. 2011, 40, 5084) with an aryl halide or heteroaryl halide 3h (wherein LG is preferably Br, I or OTf), and the reaction is carried out using a suitable catalyst (such as Pd(OAc)2 / PPh3, Pd(PPh3)4, preferably PdCh(PPh3)4) in the presence of Cui and a suitable base (such as, for example, K2CO3, CS2CO3, DIPEA or preferably TEA) and a suitable solvent (such as, for example, THF, DMSO, DMF, NMP, CH3CN or dioxane, preferably THF) and at a temperature range between room temperature and 100°C (preferably about 65°C) to give intermediate 9 ( Step a ).

[1362] The protecting group was removed from intermediate 3h using methods known in the art.

[1363] (For example, the Boc group is cleaved using TFA in DCM or 4M HCl in dioxane at temperatures between 0°C and room temperature.

[1364] The Cbz group is removed using hydrogen in the presence of a suitable catalyst such as

[1365] In the presence of activated carbon-supported Pd or Pd(OH)2 in a suitable solvent such as MeOH, EtOH, EtOAc or a mixture thereof

[1366] Remove; and as described in, for example, the following document: "Protective Groups in OrganicChemistry", from TW

[1367] Greene and PGM Wuts, 4th edition, 2006, Wiley NY) to provide intermediate 1h (step b).

[1368] In some embodiments, intermediate 3 is a 3i-type intermediate. 1 , R 2 , R 3 , A and B as described herein) can be obtained by methods known in the art and as Solution 11 The preparations were exemplified by the general synthetic procedures outlined in .

[1369]

[1370] Intermediate 3i can be prepared from alcohol 5i (commercially available or by methods known to those skilled in the art, and wherein PG is a suitable protecting group such as methyl, ethyl or tert-butyl) by reacting with compound 4i (wherein FG is a suitable leaving group such as chloro, bromo, iodo, OSO 2 Alkyl (e.g. methanesulfonic acid), OSO 2 Fluoroalkyl (e.g. trifluoromethanesulfonic acid) or OSO 2 The alkylation of the aryl group (e.g. p-toluenesulfonic acid) using a suitable base (such as sodium hydride, Huenig's base or potassium tert-butoxide) in a suitable solvent (e.g. in DMF or THF) at a temperature between 0°C and the boiling temperature of the solvent ( Step a ).

[1371] Intermediate 3i can be prepared from aldehyde or ketone 6i (commercially available or prepared by methods known to those skilled in the art, and wherein PG is a suitable protecting group such as methyl, ethyl or tert-butyl) by reductive etherification with compound 4i (wherein FG is a hydroxyl group) using a suitable reagent (such as, for example, Et3SiH and bismuth (III) chloride) in an appropriate solvent (e.g., in DCM) at a temperature between 0°C and the boiling temperature of the solvent, or using conditions as described in the literature (e.g., S. Hatakeyama, Tetrahedron Letters, Vol. 35, No. 25, pp. 4367-4370, 1994) ( Step b ).

[1372] The protecting groups are removed from intermediate 3i using methods known in the art (e.g., removal of methyl groups using LiOH or NaOH in a mixture of water and, for example, THF or 1,4-dioxane at temperatures between 0° C. and room temperature; removal of tert-butyl groups using a suitable acid such as HCl or TFA in a suitable solvent such as AcOH, DCM, or mixtures thereof; and as described, for example, in “Protective Groups in Organic Chemistry” by TW Greene and PGM Wuts, 4th edition, 2006, Wiley NY) to provide intermediate 3a ( Step c ).

[1373] In one aspect, the present invention provides a method of making a compound of formula (IA) or (IB) as described herein, the method comprising:

[1374] (a) an amine of formula 2, wherein p, q and R 4 As stated in this article,

[1375]

[1376] with carboxylic acid 3a, where L, A, B and R 1 To R 3 As described in this article

[1377]

[1378] In coupling reagents such as CDI, DCC, HATU, HBTU, HOBT, TBTU, T 3 P

[1379] or the presence of a reagent, and optionally in the presence of a base such as TEA, DIPEA (Huenig's base) or DMAP, to form the compound of formula (IB), wherein A, B, L, p, q and R 1 To R 4 As defined in this article

[1380] or (b) an amine of formula 2, wherein p, q and R 4 As stated in this article,

[1381]

[1382] With carboxylic acid chloride 3b, where L, A, B and R 1 To R 3 As described in this article

[1383]

[1384] In the presence of a base such as TEA, Huenig's base, pyridine, DMAP or lithium bis(trimethylsilyl)amide, to form the compound of formula (IB), wherein A, B, L, p, q and R 1 To R 4 as defined herein; or

[1385] c) making a first amine of formula 1, wherein A, B, L and R 1 To R 3 As stated in this article,

[1386]

[1387] and a second amine 2, wherein X, Y and Z are as described herein,

[1388]

[1389] In the presence of a base such as sodium bicarbonate and a urea-forming agent such as bis(trichloromethyl) carbonate, phosgene, trichloromethyl chloroformate, (4-nitrophenyl) carbonate or 1,1'-carbonyldiimidazole, to form the compound of formula (IA), wherein A, B, L, p, q and R 1 To R 4 As this article

[1390] Defined

[1391]

[1392] In one aspect, the present invention provides a compound of formula (I) as described herein, manufactured according to any of the methods described herein.

[1393] MAGL inhibitory activity

[1394] 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.

[1395] In another aspect, the invention provides a compound of formula (I) as described herein for use in a method of inhibiting MAGL in a mammal.

[1396] In another aspect, the present invention provides the use of a compound of formula (I) as described herein for the preparation of a medicament for inhibiting MAGL in a mammal.

[1397] In another aspect, the present invention provides a method for inhibiting MAGL in a mammal, the method comprising administering to the mammal an effective amount of a compound of formula (I) as described herein.

[1398] Compounds are analyzed for their inhibitory activity against MAGL by determining enzymatic activity following hydrolysis of the natural substrate 2-arachidonoylglycerol to arachidonic acid, which can then be subjected to mass spectrometry analysis. This assay is hereinafter abbreviated as the "2-AG assay".

[1399] The 2-AG assay was performed in a 384-well assay plate (PP, Greiner catalog number 784201) with a total volume of 20 μL. Compound dilutions were prepared in 100% DMSO (VWR Chemicals 23500.297) using a 3-fold dilution step in a polypropylene plate to allow the final concentration range of the assay to be 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, 03690-100 ml), 0.01% (v / v) Tween). After shaking, the plate was incubated at RT for 15 min. 10 μL of 2-arachidonoylglycerol in assay buffer was added to start the reaction. The final concentrations in this assay were 50 pM MAGL and 8 μM 2-arachidonoylglycerol. After shaking and incubation at RT for 30 minutes, 40 μL of acetonitrile containing 4 μM d8-arachidonic acid was added to quench the reaction. The content of arachidonic acid was tracked using an online SPE system (Agilent Rapidfire) coupled to a triple quadrupole mass spectrometer (Agilent 6460). In the acetonitrile / water liquid position, a C18 SPE cartridge (G9205A) was used. The mass spectrometer was operated in negative electrospray mode, with a mass ion pair of arachidonic acid of 303.1→259.1 and a mass ion pair of d8-arachidonic acid of 311.1→267.0. The activity of the compound was calculated based on the intensity ratio of [arachidonic acid / d8-arachidonic acid].

[1400] Table 1

[1401]

[1402]

[1403]

[1404]

[1405]

[1406]

[1407]

[1408]

[1409]

[1410]

[1411]

[1412] In one aspect, the present invention provides a compound of formula (I) as described herein and a pharmaceutically acceptable salt or ester thereof, wherein the compound of formula (I) and a pharmaceutically acceptable salt or ester thereof has a MAGL inhibition IC of less than 25 μM, preferably less than 10 μM, more preferably less than 5 μM. 50 , as measured in the MAGL assay described herein.

[1413] In one embodiment, the compounds of formula (I) and their pharmaceutically acceptable salts or esters as described herein have an IC between 0.000001 μM and 25 μM. 50 (MAGL inhibition) values, with specific compounds having IC between 0.000005 μM and 10 μM 50 values, and other specific compounds had IC values ​​between 0.00005 μM and 5 μM. 50 Value as measured in the MAGL assay described herein.

[1414] MAGL NanoBRET TM Target Engagement Assay

[1415] Compounds were expressed via the novel Cell MAGL NanoBRET TM The assay was performed using a target engagement assay that measures the apparent affinity of test compounds by competitive displacement of a Roche-developed tracer that binds to Luciferase-MAGL fusion protein binds reversibly.

[1416] The tracer developed by Roche is described in WO2021058443 (Example 21) and has the following structure:

[1417]

[1418] A HEK293A stable cell line expressing NanoLuc_MAGL was established at Roche and designated HEK293A_NanoLuc_MAGL clone #43. A fixed concentration of tracer was added to the expressing _MAGL fusion protein to generate BRET reporter complexes. Introduction of competing compounds results in NanoBRET TM A dose-dependent decrease in energy transfer occurs, allowing quantification of the intracellular affinity of the target protein for the test compound.

[1419] HEK293A_NanoLuc_MAGL clone #43 cells were cultured in DMEM (Gibco 31966) with 10% FBS and 800ug / ml G418. The NanoBRET assay was performed by seeding 5000 cells / well in a Costar small volume white 384-well plate filled with assay buffer (1% FBS in HBSS), followed by the addition of 50nM final concentration of tracer and serial dilutions of the test compound. After 2 hours of incubation, Nanoluciferase substrates and extracellular inhibitors were added according to the manufacturer's protocol (Promega, #N2520), and NanoBRET signal transduction was quantified using Paradigm (Molecular Devices).

[1420]

[1421]

[1422] In one aspect, the present invention provides a compound of formula (I) as described herein and a pharmaceutically acceptable salt or ester thereof, wherein the compound of formula (I) and a pharmaceutically acceptable salt or ester thereof has a MAGL NanoBRET target engagement assay IC of less than 25 μM, preferably less than 10 μM, more preferably less than 5 μM. 50 , as measured in the MAGL assay described herein.

[1423] In one embodiment, the compounds of formula (I) and their pharmaceutically acceptable salts or esters as described herein have an IC between 0.0001 μM and 25 μM. 50 (MAGL inhibition) values, with specific compounds having IC between 0.0005 μM and 10 μM 50 values, other specific compounds had IC values ​​between 0.001 μM and 5 μM 50 Value as measured in the MAGL assay described herein.

[1424] Use of the Compounds of the Invention

[1425] 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.

[1426] In another aspect, the present invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein for treating or preventing neuroinflammation, neurodegenerative diseases, pain, cancer, mental disorders and / or inflammatory bowel disease in a mammal.

[1427] In one embodiment, the present invention provides a use of a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein for treating or preventing neuroinflammatory and / or neurodegenerative diseases in a mammal.

[1428] In one embodiment, the present invention provides a use of a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein for treating or preventing a neurodegenerative disease in a mammal.

[1429] In one embodiment, the present invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein for treating or preventing cancer in a mammal.

[1430] In one embodiment, the invention provides the use of a compound of formula (I) as described herein for treating or preventing inflammatory bowel disease in a mammal.

[1431] In one embodiment, the present invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein for treating or preventing pain in a mammal.

[1432] In one aspect, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof for use in 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 spasms, abdominal pain, abdominal pain associated with irritable bowel syndrome and / or visceral pain in a mammal.

[1433] In a preferred embodiment, the present invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein for treating or preventing multiple sclerosis, Alzheimer's disease and / or Parkinson's disease in a mammal.

[1434] 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 treating or preventing multiple sclerosis in a mammal.

[1435] In one aspect, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof for use in treating or preventing neuroinflammation, neurodegenerative diseases, pain, cancer, psychiatric disorders and / or inflammatory bowel disease in a mammal.

[1436] In one embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof for use in treating or preventing neuroinflammatory and / or neurodegenerative diseases in a mammal.

[1437] In one embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof for use in treating or preventing cancer in a mammal.

[1438] In one embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof for use in treating or preventing a neurodegenerative disease in a mammal.

[1439] In one embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof for use in treating or preventing inflammatory bowel disease in a mammal.

[1440] In one embodiment, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof for use in treating or preventing pain in a mammal.

[1441] In one aspect, the present invention provides a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof for use in 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 spasms, abdominal pain, abdominal pain associated with irritable bowel syndrome and / or visceral pain in a mammal.

[1442] 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 treating or preventing multiple sclerosis, Alzheimer's disease and / or Parkinson's disease in a mammal.

[1443] 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 treating or preventing multiple sclerosis in a mammal.

[1444] In one aspect, the present invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein for preparing a medicament for treating or preventing neuroinflammation, neurodegenerative diseases, pain, cancer, mental disorders and / or inflammatory bowel disease in a mammal.

[1445] 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 preparing a medicament for treating or preventing neuroinflammatory and / or neurodegenerative diseases in mammals.

[1446] 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 preparing a medicament for treating or preventing a neurodegenerative disease in a mammal.

[1447] 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 preparing a medicament for treating or preventing cancer in a mammal.

[1448] 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 preparing a medicament for treating or preventing inflammatory bowel disease in a mammal.

[1449] 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 preparing a medicament for treating or preventing pain in a mammal.

[1450] In another aspect, the present invention provides the use of a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof for preparing a medicament 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 carcinoma, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, pain-related spasms, abdominal pain, abdominal pain associated with irritable bowel syndrome and / or visceral pain in a mammal.

[1451] 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 preparing a medicament for treating or preventing multiple sclerosis, Alzheimer's disease and / or Parkinson's disease in a mammal.

[1452] 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 preparing a medicament for treating or preventing multiple sclerosis in a mammal.

[1453] In one aspect, the present invention provides a method for treating or preventing neuroinflammation, neurodegenerative diseases, pain, cancer, mental 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.

[1454] In one embodiment, the present invention provides a method for treating or preventing neuroinflammatory and / or neurodegenerative diseases 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.

[1455] In one embodiment, the present invention provides a method for treating or preventing a neurodegenerative 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.

[1456] In one embodiment, the present invention provides a method for treating or preventing cancer 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.

[1457] In one embodiment, the present invention provides a method for treating or preventing inflammatory bowel 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.

[1458] In one embodiment, the present invention provides a method for treating or preventing 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.

[1459] In another aspect, the present invention provides a method for treating or preventing multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, anxiety, migraine, depression, hepatocellular carcinoma, colon carcinoma, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, spasm associated with pain, abdominal pain, abdominal pain associated with irritable bowel syndrome and / or visceral pain 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.

[1460] In a preferred embodiment, the present invention provides a method for treating or preventing 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.

[1461] In a particularly preferred embodiment, the present invention provides a method for treating or preventing 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.

[1462] Pharmaceutical compositions and administration

[1463] In one aspect, the present invention provides a pharmaceutical composition comprising a compound of formula (I) as described herein and a therapeutically inert carrier.

[1464] In one embodiment, the present invention provides the pharmaceutical compositions disclosed in Examples 866 and 867.

[1465] The compounds of formula (I) and their pharmaceutically acceptable salts and esters can be used as medicaments (e.g., in the form of pharmaceutical preparations). Pharmaceutical preparations can be administered internally, such as orally (e.g., in the form of tablets, coated tablets, lozenges, hard and soft gelatin capsules, solutions, emulsions or suspensions), intranasally (e.g., in the form of nasal sprays) or rectally (e.g., in the form of suppositories). However, they can also be administered parenterally, such as intramuscularly or intravenously (e.g., in the form of injections).

[1466] The compound of formula (I) and its pharmaceutically acceptable salts and esters can be processed with pharmaceutically inert, inorganic or organic adjuvants to form tablets, coated tablets, dragees and hard gelatin capsules. For example, lactose, corn starch or its derivatives (talc, stearic acid or its salts, etc.) can be used as such adjuvants for tablets, dragees and hard gelatin capsules.

[1467] Suitable adjuvants for soft gelatin capsules are, for example, vegetable oils, waxes, fats, semisolid substances and liquid polyols and the like.

[1468] Suitable adjuvants for the preparation of solutions and syrups are, for example, water, polyols, sucrose, invert sugar, glucose and the like.

[1469] Suitable adjuvants for injection solutions are, for example, water, alcohols, polyols, glycerol, vegetable oils and the like.

[1470] Suitable adjuvants for suppositories are, for example, natural or hardened oils, waxes, fats, semi-solid or liquid polyols and the like.

[1471] In addition, the pharmaceutical preparations may contain preservatives, solubilizers, viscosity-increasing substances, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavorings, salts for varying the osmotic pressure, buffer masking agents or antioxidants. They may also contain other therapeutically valuable substances.

[1472] The dosage can vary within a wide range and will of course be adapted to the various requirements in each particular case. In general, a daily dosage of about 0.1 mg to 20 mg per kg body weight, preferably about 0.5 mg to 4 mg per kg body weight (e.g. about 300 mg per person) for oral administration should be suitable, preferably divided into 1-3 separate doses (which may consist of, for example, the same amount). However, it is apparent that, when indicated as indicated, the upper limit given herein may be exceeded.

[1473] Examples

[1474] The present invention will be more fully understood by reference to the following examples. However, the claims should not be interpreted as being limited to the scope of the examples.

[1475] Where the preparation examples are obtained as mixtures of enantiomers, the pure enantiomers can be separated by methods described herein or by methods known to those skilled in the art such as chiral chromatography (eg chiral SFC) or crystallization.

[1476] If not stated otherwise, all reaction examples and intermediates were prepared under argon atmosphere.

[1477] Separation methods

[1478] HPLC Method GN

[1479] Gemini NX, 12 nm, 5 μm, 100 x 30 mm, 15 min gradient, ACN / water + 0.1% FA

[1480] HPLC Method YMC

[1481] YMC-Triart C18, 12nm, 5μm, 100x30mm, gradient, ACN / water + 0.1% FA

[1482] Chiral separation methods

[1483] HPLC method OD1

[1484] Chiralcel OD, normal phase (isocratic): 80% heptane; 20% ethanol + NH4Oac

[1485] HPLC Method OD2

[1486] Chiralcel OD, normal phase (isocratic): 60% heptane; 40% ethanol + NH4Oac

[1487] HPLC Method AD

[1488] Chiralpak-AD, normal phase (isocratic): 60% heptane; 40% ethanol + NH4Oac

[1489] HPLC Method AD1

[1490] Chiralpak-AD, normal phase (isocratic): 70% heptane; 30% ethanol + NH4Oac

[1491] HPLC Method NR

[1492] Reprosil chiral NR, normal phase (isocratic): 60% heptane; 40% ethanol + NH4Oac

[1493] SFC MethodAY

[1494] (AY-H, 12 nm, 5 μm, 250 x 4.6 mm column), eluent: 30% MeOH in supercritical CO2

[1495] SFC Method ADH

[1496] (AD-H, 12 nm, 5 μm, 250 x 4.6 mm), eluent: 40% MeOH in supercritical CO2

[1497] SFC Method ADH1

[1498] (AD-H, 12 nm, 5 μm, 250 x 4.6 mm), eluent: 20% MeOH in supercritical CO2

[1499] SFC Method ADH2

[1500] (AD-H, 12 nm, 5 μm, 250 x 4.6 mm), eluent: 30% IPA (0.1% NH3·H2O) in supercritical CO2

[1501] SFC method ADH3

[1502] (AD-H, 12 nm, 5 μm, 250 x 4.6 mm), eluent: 40% MeOH (0.1% NH3·H2O) in supercritical CO2

[1503] SFC Method IC

[1504] (IC, 12 nm, 5 μm, 250 x 20 mm), eluent: 25% EtOH in supercritical CO2

[1505] SFC Method IC1

[1506] (IC, 12 nm, 5 μm, 250 x 20 mm), eluent: 35% EtOH in supercritical CO2

[1507] SFC Method IA

[1508] IA, 12nm, 5μm, 250x20mm, 20% EtOH in supercritical CO2

[1509] SFC Method IG

[1510] (IG, 12 nm, 5 μm, 250 x 20 mm), eluent: 40% MeOH (0.1% NH 3 ·H 2 O) in supercritical CO 2

[1511] SFC Method IH

[1512] (IH, 5 μm, 250 x 20 mm), eluent: 35% MeOH in supercritical CO2

[1513] SFC Method OJH

[1514] OJ-H, 12 nm, 5 μm, 250 x 20 mm, 15% EtOH in supercritical CO2

[1515] SFC Method OJH1

[1516] OJ-H, 12nm, 5μm, 250x20mm, 20% EtOH in supercritical CO2

[1517] SFC Method OJH2

[1518] OJ-H, 12nm, 5μm, 250x20mm, 25% IPA in supercritical CO2

[1519] SFC Method ODH

[1520] OD-H, 12nm, 5μm, 250x4.6mm. 20-40% EtOH in supercritical CO2

[1521] SFC Method ODH1

[1522] OD-H, 5nm, 5μm, 250x20mm. 30% MeOH in supercritical CO2

[1523] SFC Method OD

[1524] Chiralcel OD, 250mm*30mm, 10um, 40% IPA (0.1% NH3·H2O) in supercritical CO2

[1525] SFC Method OD1

[1526] Chiralcel OD, 250mm*30mm, 10um, 55% IPA (0.1% NH3·H2O) in supercritical CO2

[1527] SFC Method OD3

[1528] Chiralcel OD, 250mm*30mm, 10um, 55% EtOH (0.1% NH3·H2O) in supercritical CO2

[1529] SFC Method OD4

[1530] Chiralcel OD, 250mm*30mm, 10um, 50% IPA (0.1% NH3·H2O) in supercritical CO2

[1531] SFC Method OD5

[1532] Chiralcel OD, 250mm*30mm, 10um, 45% MeOH (0.1% NH3·H2O) in supercritical CO2

[1533] SFC Method AD

[1534] Chiralpak AD, 250mm*30mm, 10um, 40% (IPA / ACN 4 / 1) in supercritical CO2 (0.1% NH3·H2O)

[1535] SFC Method AD1

[1536] Chiralpak AD, 250mm*30mm, 10um, 50% (IPA / ACN 4 / 1) in supercritical CO2 (0.1% NH3·H2O)

[1537] SFC Method AD2

[1538] Chiralpak AD, 250mm*30mm, 10um, 55% EtOH (0.1% NH3·H2O) in supercritical CO2

[1539] SFC Method AD3

[1540] Chiralpak AD, 250mm*30mm, 10um, 45% (IPA / ACN 4 / 1) in supercritical CO2 (0.1% NH3·H2O)

[1541] SFC Method AD4

[1542] Chiralpak AD, 250mm*30mm, 10um, 30% EtOH in supercritical CO2

[1543] SFC Method AD5

[1544] Chiralpak AD, 250mm*30mm, 10um, 60% (MeOH / ACN 3 / 1) (0.1% NH3·H2O) in supercritical CO2

[1545] SFC Method AD6

[1546] Chiralpak AD, 250mm*30mm, 10um, 30% MeOH (0.1% NH3·H2O) in supercritical CO2

[1547] SFC Method AD7

[1548] Chiralpak AD, 250mm*30mm, 10um, in supercritical CO 2 50% MeOH (0.1% NH3·H2O)

[1549] SFC Method CE

[1550] Cellulose-4, 20X 350mm, 5um, in supercritical CO 2 35% MeOH (0.2% DEA)

[1551] Example 1

[1552] [3-[[2-Fluoro-6-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone

[1553]

[1554] To carbonate bis (trichloromethyl) ester (80mg, 270μmol, CAS RN 32315-10-9) and NaHCO (118mg, 1.4mmol) ice-cold suspension in DCM (1.5mL) add 3- ((2- fluoro- 6- (trifluoromethyl) benzyl) oxy) azetidine hydrochloride (100mg, 350μmol, CAS RN 1121613-07-7) solution in DCM (1.5mL), and the mixture is stirred at room temperature overnight. 5- (pyrrolidin-3-yl) -1H- pyrazole dihydrochloride (48mg, 228μmol, CASRN 2173135-18-5) and DIPEA (313μL, 1.79mmol) are added to the suspension. The suspension is stirred at room temperature for 3.5 hours. The reaction mixture is poured on water and DCM, and the layers are 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] + .

[1555] If not otherwise indicated, the following examples were synthesized using appropriate building blocks following synthetic methods similar to those described for Example 1, respectively.

[1556]

[1557]

[1558]

[1559]

[1560]

[1561] Example 4

[1562] (+)- or (-)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone

[1563] and Example 5

[1564] (-)- or (+)-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone

[1565]

[1566] The racemate of [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) as a yellow oil (37 mg, 14.6%). MS (ESI): m / z = 413.3 [M+H] + .

[1567] If not otherwise indicated, the following examples were isolated using appropriate starting materials following synthetic methods similar to those described for Example 4 and Example 5, respectively.

[1568]

[1569]

[1570]

[1571]

[1572]

[1573]

[1574]

[1575]

[1576]

[1577]

[1578]

[1579]

[1580]

[1581]

[1582]

[1583] Example 6

[1584] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(4-methyl-1H-pyrazol-5-yl)azetidin-1-yl]methanone

[1585]

[1586] To a solution of 5-(azetidin-3-yl)-4-methyl-1H-pyrazole 2,2,2-trifluoroacetic acid (38 mg, 151 μmol, CASRN 1361115-19-6) in DCM (1 mL) was added DIPEA (79 μL, 151 μmol) followed by a single addition of di(1H-1,2,4-triazol-1-yl)methanone (23.6 mg, 144 μmol). The mixture was stirred at room temperature for 1 hour. After a single addition of 3-((2-fluoro-4-(trifluoromethyl)benzyl)oxy)azetidine 4-methylbenzenesulfonic acid (CAS RN 2135785-94-1), 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] + .

[1587] If not otherwise indicated, the following examples were synthesized using appropriate building blocks following similar synthesis methods as described respectively for Example 6. The reactions were carried out in DCM, DMF or MeCN as solvent at between 50°C and 80°C.

[1588]

[1589]

[1590]

[1591]

[1592]

[1593]

[1594]

[1595]

[1596]

[1597]

[1598]

[1599]

[1600]

[1601]

[1602]

[1603]

[1604]

[1605]

[1606]

[1607]

[1608]

[1609]

[1610]

[1611]

[1612]

[1613]

[1614]

[1615]

[1616]

[1617]

[1618]

[1619]

[1620]

[1621]

[1622]

[1623]

[1624]

[1625] Example 8

[1626] [4-[(2-Chloro-4-fluoro-phenyl)methoxy]-1-piperidinyl]-[3-(4-methyl-1H-pyrazol-5-yl)azetidin-1-yl]methanone

[1627]

[1628] To a solution of 5-(azetidine-3-yl)-4-methyl-1H-pyrazole 2,2,2-trifluoroacetic acid (20 mg, 80 μmol, CAS RN1361115-19-6) in DCM (1 mL) was added DIPEA (42 μL, 239 μmol), followed by a one-time addition of 4-nitrophenyl chloroformate (15.2 mg, 75.6 μmol, CAS RN 7693-46-1). The mixture was stirred at room temperature for 2 hours. The reaction mixture was evaporated to dryness. The residue was absorbed in dioxane (1 mL). After a one-time addition of 4-[(2-chloro-4-fluorophenyl)methoxy]piperidine (28 mg, 80 μmol, CAS RN 1098356-25-2), the mixture was stirred at room temperature for 2 hours. 2M NaOH aqueous solution (796 μl, 1.59 mmol) was added and 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 (0.002 g; 6.72%). MS (ESI): m / z = 407.2 [M+H] + .

[1629] Example 13

[1630] [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[3-(2-methylpyrazol-3-yl)pyrrolidin-1-yl]methanone

[1631]

[1632] 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 stirring was continued for 30 min. The RM was quenched with water and poured over EtOAc. The aqueous layer was extracted three times by 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 equal mass were collected. It is assumed that this is due to methylation to the desired product and tautomers. 2D NMR confirmed that the first eluting compound was the desired product, which was obtained as a colorless oil (10 mg; 12.6%). MS (ESI): m / z = 427.3 [M+H] + .

[1633] Example 17

[1634] [3-[4-(2,4-dichlorophenyl)phenyl]azetidin-1-yl]-[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone

[1635]

[1636] 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 hours. 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 with an elution 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] + .

[1637] Example 42

[1638] (+)- 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

[1639] and Example 43

[1640] (-)- 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

[1641]

[1642] 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 a one-time addition of di(1H-1,2,4-triazol-1-yl)methanone (23.5 mg, 143 μmol). The mixture was stirred at room temperature for 30 minutes. After a one-time addition of 5-(pyrrolidin-3-yl)-1H-1,2,4-triazole dihydrochloride (30.3 mg, 143 μmol, CAS RN 1909337-56-9), 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 light yellow lyophilized solid (0.022 g; 31.8%). MS (ESI): m / z=434.3 [M+H] + , and compound 43 (second elution) as a light yellow lyophilized solid (0.025 g; 36.2%). MS (ESI): m / z = 434.3 [M+H] + .

[1643] If not otherwise indicated, the following examples were synthesized using appropriate building blocks following synthetic methods similar to those described for Example 42 and Example 43, respectively.

[1644]

[1645]

[1646]

[1647]

[1648]

[1649]

[1650]

[1651]

[1652]

[1653] Example 83

[1654] trans-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]cyclobutyl]-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone

[1655]

[1656] 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) was added HATU (55 mg, 145 μmol) and DIPEA (92 μL, 0.53 mmol), and the mixture was stirred at room temperature overnight. The product was purified by HPLC method GN to give the desired compound as a light yellow oil (0.036 g; 50.5%). MS (ESI): m / z=412.2 [M+H] + .

[1657] Example 821

[1658] [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[4-[[5-(trifluoromethyl)pyrazin-2-yl]amino]cuban-1-yl]methanone

[1659]

[1660] The product was obtained analogously 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]+.

[1661] If not otherwise indicated, the following examples were synthesized using appropriate building blocks following synthetic methods similar to those described for Example 83, respectively.

[1662]

[1663]

[1664]

[1665] Example 92

[1666] [3-[4-(2-methylazetidin-1-yl)phenyl]azetidin-1-yl]-[(3S or 3R)-3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]methanone

[1667]

[1668] 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 at 25° C. for 16 h. 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 on 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] + .

[1669] If not otherwise indicated, the following examples were synthesized using appropriate building blocks following synthetic methods similar to those described for Example 92, respectively.

[1670]

[1671]

[1672]

[1673]

[1674] Example 123

[1675] (+)-[4-[(2-Chloro-4-fluoro-phenoxy)methyl]-1-piperidinyl]-[(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone

[1676] and Example 124

[1677] (-)-[4-[(2-Chloro-4-fluoro-phenoxy)methyl]-1-piperidinyl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone

[1678]

[1679] 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 h. The reaction mixture was evaporated under reduced pressure to give a residue, which was then purified on preparative HPLC (Gemini Luna C18 column) using a gradient of A: water (containing 0.225% FA) (20:80 to 98:2) and on preparative TLC (DCM / MeOH=10 / 1) to give the racemate. The racemate was then separated by SFC method AD5 to give the desired product Example 123 (first eluting) 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) as a white solid (19.6 mg, 5.7% yield). MS (ESI): m / z=408.0 [M+H] + .

[1680] Example 123. Optical rotation: +21.10°

[1681] Example 124. Optical rotation: -17.03°

[1682] Example 134

[1683] (-)-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3S or 3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone

[1684] and Example 135

[1685] (+)-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3S or 3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone

[1686] Example 136

[1687] (-)-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3S or 3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone

[1688] and Example 137

[1689] (+)-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3S or 3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone

[1690]

[1691] 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 RN 2411576-99-1) and DIPEA (1.0 mL, 2.12 mmol) in ACN (15 mL) was added (4-nitrophenyl)(3S or 3R)-3-(1H-triazol-5-yl)pyrrolidine-1-carboxylate (176.86 mg, 0.580 mmol, BB28) and the mixture was stirred at 80° C. for 12 h. The reaction mixture was poured into H2O (5 mL), extracted with EtOAc (5 mL*3), and the organic layer was evaporated. The crude product was purified with 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] + , along with an impure mixture of products 134 and 135.

[1692] The 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] + .

[1693] Example 134. Optical rotation: -56.53°

[1694] Example 135. Optical rotation: +20.36°

[1695] Example 136. Optical rotation: -38.24°

[1696] Example 137. Optical rotation: +20.12°

[1697] Example 138

[1698] (+)-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3R or 3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone

[1699] and Example 139

[1700] (-)-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3R or 3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone

[1701] Example 140

[1702] (-)-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3R or 3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone

[1703] and Example 141

[1704] (+)-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-2-methyl-azetidin-1-yl]-[(3R or 3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone

[1705]

[1706] 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 RN 2411576-99-1) and DIPEA (1.0 mL, 2.12 mmol) in ACN (15 mL) was added (4-nitrophenyl)(3R or 3S)-3-(1H-triazol-5-yl)pyrrolidine-1-carboxylate (176.86 mg, 0.580 mmol, BB29) and the mixture was stirred at 80° C. for 12 h. The reaction mixture was poured into H2O (5 mL), extracted with EtOAc (5 mL*3), and the organic layer was evaporated. The crude product was purified with 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] + , together with an impure mixture of products 140 and 141.

[1707] The 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] + .

[1708] Example 138. Optical rotation: +48.08°

[1709] Example 139. Optical rotation: -45.84°

[1710] Example 140. Optical rotation: -13.67°

[1711] Example 141. Optical rotation: +55.40°

[1712] Example 182

[1713] Sodium [3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidin-1-yl]-[rac-(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone

[1714]

[1715] 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 a 30% solution of sodium methoxide in MeOH (22.5 μL, 121 μmol) and the clear and colorless solution was stirred at room temperature for 2.5 hours. TBME (2 mL) was added dropwise. This produced a precipitate. 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 (0.035 g; 66.5%) as a colorless solid. MS (ESI): m / z=414.2 [M+H] + .

[1716] Analogously to Examples 1 to 841, the following examples were prepared using building blocks similar to building blocks BB1 to BB119 described in this application, which are either commercially available or synthesized by a person skilled in the art.

[1717]

[1718]

[1719]

[1720]

[1721]

[1722]

[1723]

[1724]

[1725]

[1726]

[1727]

[1728]

[1729]

[1730]

[1731]

[1732]

[1733]

[1734]

[1735]

[1736]

[1737]

[1738]

[1739]

[1740]

[1741]

[1742]

[1743]

[1744]

[1745]

[1746]

[1747]

[1748]

[1749]

[1750]

[1751]

[1752]

[1753]

[1754]

[1755]

[1756]

[1757]

[1758]

[1759]

[1760]

[1761]

[1762]

[1763]

[1764]

[1765]

[1766]

[1767]

[1768]

[1769]

[1770]

[1771]

[1772]

[1773]

[1774]

[1775]

[1776]

[1777]

[1778]

[1779]

[1780]

[1781]

[1782]

[1783]

[1784]

[1785]

[1786]

[1787]

[1788]

[1789]

[1790]

[1791]

[1792]

[1793]

[1794]

[1795]

[1796]

[1797]

[1798]

[1799]

[1800]

[1801]

[1802]

[1803]

[1804]

[1805]

[1806]

[1807]

[1808]

[1809]

[1810]

[1811]

[1812]

[1813]

[1814]

[1815]

[1816]

[1817]

[1818]

[1819]

[1820]

[1821]

[1822]

[1823]

[1824]

[1825]

[1826]

[1827]

[1828] Synthesis of building blocks

[1829] BB 1

[1830] 6-(2-Chloro-4-fluoro-phenoxy)-2-azaspiro[3.3]heptane 2,2,2-trifluoroacetic acid

[1831] Step 1: 6-(2-Chloro-4-fluoro-phenoxy)-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester

[1832] At 0 ℃, to 2-chloro-4-fluorophenol (756mg, 562 μ l, 5.16mmol, CAS RN 1996-41-4), 6-hydroxy-2-azaspiro [3.3] heptane-2-carboxylic acid tert-butyl ester (1g, 4.69mmol, CAS RN 1147557-97-8) and triphenylphosphine (1.48g, 5.63mmol) in THF (23.4ml) solution dropwise add DIAD (1.09ml, 5.63mmol, CAS N 2446-83-5), and the reaction is stirred at room temperature for 18h.Add another batch of triphenylphosphine (738mg, 2.81mmol), then add DIAD (547 μ l, 2.81mmol), and the reaction is stirred at room temperature for 6h.Reaction mixture is poured into saturated NaHCO in the aqueous solution (50mL), and EtOAc (30mL) is 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 fixed on Isolute and purified by column chromatography (40 gr, 0->30% EtOAc in heptane) to give the desired product as a yellow solid (1.50 g, 89.3% yield). MS (ESI): m / z=286.2 [M-C4H8+H] + .

[1833] Step 2: 6-(2-Chloro-4-fluoro-phenoxy)-2-azaspiro[3.3]heptane 2,2,2-trifluoroacetic acid

[1834] 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] + .

[1835] BB 2

[1836] 3-((2-Fluoro-4-(pentafluoro-16-thio)benzyl)oxy)azetidine 2,2,2-trifluoroacetic acid

[1837] Step 1: tert-Butyl 3-((2-fluoro-4-(pentafluoro-16-thio)benzyl)oxy)azetidine-1-carboxylate

[1838] To a solution of tert-butyl 3-hydroxyazetidine-1-formate (5.5 g, 31.8 mmol, CAS RN 141699-55-0) in anhydrous THF (4 ml) was added a 1 M solution of potassium tert-butoxide in THF (33.3 ml, 33.3 mmol), and the turbid reaction mixture was stirred at room temperature for 15 min, followed by 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 was diluted with EtOAc and extracted with water, the organic phase was collected and the aqueous phase was stripped 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] + .

[1839] Step 2: 3-((2-fluoro-4-(pentafluoro-16-thio)benzyl)oxy)azetidine 2,2,2-trifluoroacetic acid

[1840] 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] + .

[1841] BB 3

[1842] (3-(1H-pyrazol-5-yl)pyrrolidin-1-yl)(3-(4-bromophenyl)azetidin-1-yl)methanone

[1843] The product was obtained analogously 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]+.

[1844] BB 4

[1845] 6-Pyrrolidin-3-yl-1H-pyrazin-2-one hydrobromide

[1846] 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] + .

[1847] BB 5

[1848] (+) or (-)-[1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidin-3-yl]oxazolidin-2-one

[1849] and

[1850] BB 6

[1851] (-) or (+)-[1-[3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidin-3-yl]oxazolidin-2-one

[1852] 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 eluting) as a colorless solid (21.3 mg, 4.33%). MS (ESI): m / z = 432.2 [M+H] + , and the desired product BB6 (second elution) as a colorless solid (59.5 mg, 12.1%). MS (ESI): m / z = 432.2 [M+H] + .

[1853] BB 7

[1854] 5-Pyrrolidin-3-ylpyrrolidin-2-one 4-methylbenzenesulfonic acid [Entity A]

[1855] Step 1: tert-Butyl 3-[1-(Benzyloxycarbonylamino)-2-methoxy-2-oxo-ethyl]pyrrolidine-1-carboxylate

[1856] Under vigorous stirring, to tert-butyl 3-(1-amino-2-methoxy-2-oxoethyl)pyrrolidine-1-formate (1.5 g, 5.81 mmol, CAS RN 1135916-70-9) in DCM (15 mL) and NaHCO saturated solution (solution in H O) (10 mL, 5.81 mmol) at room temperature benzyl chloroformate (829 μL, 5.81 mmol) was added dropwise over 80 minutes. The two-layer mixture was stirred at room temperature for 20 minutes. 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 with an elution gradient of n-heptane:EtOAc (100:0 to 30:70) to afford the desired compound as a colorless oil (2.06 g; 88.6%). MS (ESI): m / z = 293.2 [M-BOC+H] + .

[1857] Step 2: tert-Butyl 3-[1-(Benzyloxycarbonylamino)-2-hydroxy-ethyl]pyrrolidine-1-carboxylate [Entity A] and 3-[1-(Benzyloxycarbonylamino)-2-hydroxy-ethyl]pyrrolidine-1-carboxylic acid tert-butyl ester [Entity B]

[1858] 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 2M solution of LiBH4 in THF (4.36 mL, 8.71 mmol). The clear solution was stirred at room temperature for 2 hours. The reaction mixture was poured onto a saturated aqueous solution of sodium potassium 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 MgSO4, filtered, treated with silica gel, and evaporated. The compound was purified three times by silica gel chromatography on an 80 g chromatography column using an MPLC system with an elution gradient of n-heptane: EtOAc (100:0 to 0:100) to obtain the desired products [Entity A] (first elution) and [Entity B] (second elution). MS (ESI): m / z=265.2[M-C4H8+H]+.

[1859] Step 3: tert-Butyl 3-[1-(Benzyloxycarbonylamino)-2-oxo-ethyl]pyrrolidine-1-carboxylate [Entity A]

[1860] To an ice-cold solution of tert-butyl 3-[1-(benzyloxycarbonylamino)-2-hydroxy-ethyl]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 hours. The reaction mixture was diluted with DCM and 2M 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, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 12 g chromatography column using an MPLC system with an elution 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] + .

[1861] Step 4: 3-[(E)-1-(Benzyloxycarbonylamino)-4-ethoxy-4-oxo-but-2-enyl]pyrrolidine-1-carboxylate Tert-butyl ester [Entity A]

[1862] 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-formate (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 water 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 with an elution gradient of n-heptane:EtOAc (100:0 to 50:50) to afford the desired compound as a colorless gum (0.519 g; 73.8%). MS (ESI): m / z = 377.2 [M-C4H8+H] + .

[1863] Step 5: tert-Butyl 3-(5-oxopyrrolidin-2-yl)pyrrolidine-1-carboxylate [Entity A]

[1864] 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 for 4.5 hours in a sealed tube. The reaction mixture was filtered. The filtrate was evaporated. The residue was absorbed in a diluted aqueous NaHCO3 solution 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] + .

[1865] Step 6: 5-Pyrrolidin-3-ylpyrrolidin-2-one 4-methylbenzenesulfonic acid [Entity A]

[1866] 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 to reflux for 1 hour and then 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 obtain the desired compound as a light yellow solid (0.085 g; 72.4%). MS (ESI): m / z=155.1 [M+H] + .

[1867] BB 8

[1868] 5-Pyrrolidin-3-ylpyrrolidin-2-one 4-methylbenzenesulfonic acid [Entity B]

[1869] The product was obtained analogously to BB7, steps 3 to 6, starting from tert-butyl 3-[1-(benzyloxycarbonylamino)-2-hydroxy-ethyl]pyrrolidine-1-carboxylate [Entity B] (BB7, step 2) to give the title compound as a colorless solid. MS (ESI): m / z=155.1 [M+H] + .

[1870] BB 9

[1871] 3-[4-[1-(Trifluoromethyl)cyclopropyl]phenyl]azetidine 4-methylbenzenesulfonic acid

[1872] Step 1: tert-Butyl 3-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]azetidine-1-carboxylate

[1873] To a 20 mL vial equipped with a stir bar was added 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 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)pyridinium 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). The vial was sealed and placed under Ar, and then dimethoxyethane (9 mL) was added. Nickel chloride (II) glycol dimethyl ether complex (4.65mg, 21.2μmol, 0.01 equivalent; CAS RN 29046-78-4) and 4,4'-di-tert-butyl-2,2'-bipyridine (5.68mg, 21.2μmol, 0.01 equivalent) were added to another vial. The vial was sealed, purged with Ar, and dimethoxyethane (4mL) was added. The precatalyst solution was ultrasonically treated for 5min, and then 2mL of the solution was injected into the reaction vessel. The reaction mixture was degassed with Ar and irradiated with a blue LED lamp (420nm) for 1h. 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, and the elution gradient was n-heptane: EtOAc (100:0 to 70:30), to obtain the title compound, which was a colorless solid (0.51g, 66%). MS(ESI): m / z=286.1[M-C4H8+2H] + .

[1874] Step 2: 3-[4-[1-(Trifluoromethyl)cyclopropyl]phenyl]azetidine 4-methylbenzenesulfonic acid

[1875] 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 to reflux for 2 h. The suspension was placed in a refrigerator and cooled at 0 ° C. 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]+ .

[1876] BB 10

[1877] 6-(2,4-Difluorobenzyl)-2-azaspiro[3.3]heptane 2,2,2-trifluoroacetic acid

[1878] Step 1: (2,4-Difluorobenzyl)triphenylphosphonium bromide

[1879] 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. 250 mL of TBME was added thereto and stirred at room temperature for 30 min. 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] + .

[1880] Step 2: tert-Butyl 6-(2,4-difluorobenzylidene)-2-azaspiro[3.3]heptane-2-carboxylate

[1881] Under argon at -78 ° C, (2,4-difluorobenzyl) triphenylphosphonium bromide (4.6g, 9.8mmol) is dissolved in anhydrous THF (46ml), and a solution of LHMDS1M in THF (19.6ml, 19.6mmol) is added. The reaction mixture is stirred for 2 hours at -78 ° C. Then at room temperature, 6-oxo-2-azaspiro [3.3] heptane-2-tert-butyl formate (4.14g, 19.6mmol, CAS RN 1181816-12-5) is added, and the mixture is stirred overnight at 85 ° C. After cooling, TBME is added. The suspension is filtered. The filtrate is concentrated and then purified by flash chromatography (silica gel, 100g, 0% to 80% EtOAc in heptane). The residue is treated with toluene and evaporated to obtain the desired product, which is a yellow oil (10.1g, 100%). 308.1[M+H] + .

[1882] Step 3: tert-Butyl 6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptane-2-carboxylate

[1883] 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 (x3). 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 pad of celite, washed with EtOAc and dried under vacuum to give the desired crude product (1.44 g, 86.2%). 268.2 [M-C4H8+H] + .

[1884] Step 4: 6-(2,4-difluorobenzyl)-2-azaspiro[3.3]heptane 2,2,2-trifluoroacetic acid

[1885] 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] + .

[1886] BB 11

[1887] 2-[2-Fluoro-4-(trifluoromethyl)phenoxy]-7-azaspiro[3.5]nonane 2,2,2-trifluoroacetic acid

[1888] Step 1: tert-Butyl 2-[2-fluoro-4-(trifluoromethyl)phenoxy]-7-azaspiro[3.5]nonane-7-carboxylate

[1889] To a solution of 2-hydroxy-7-azaspiro [3.5] nonane-7-tert-butyl formate (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 in 10 minutes. After stirring in an ice bath for 1 hour, the mixture was stirred at room temperature for 5 hours. The reaction mixture was poured onto water and ether, and each layer was separated. The organic layer was washed with water, a 1 M NaOH aqueous solution 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 with an elution gradient of n-heptane:EtOAc (100:0 to 60:40) to afford the desired compound as a colorless solid (0.625 g; 83.9%). MS (ESI): m / z = 348.1 [M-C4H8+H] + .

[1890] Step 2: 2-[2-Fluoro-4-(trifluoromethyl)phenoxy]-7-azaspiro[3.5]nonane 2,2,2-trifluoroacetic acid

[1891] 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 hours. The solution was evaporated to give the desired product as a colorless solid (0.073 g, 100%). 304.2 [M+H] + .

[1892] BB12

[1893] 3-[4-(2,4-Difluorophenyl)phenyl]azetidine 4-methylbenzenesulfonic acid

[1894] Step 1: tert-Butyl 3-[4-(2,4-difluorophenyl)phenyl]azetidine-1-carboxylate

[1895] By tert-butyl 3- (4- bromophenyl) azetidine -1- formates (1.3g, 4.16mmol, CAS RN 1203681-52-0), (2,4- difluorophenyl) boronic acid (658mg, 4.16mmol, CAS RN 144025-03-6), potassium carbonate (2.88g, 20.8mmol), water (1ml) and tetrakis (triphenylphosphine) palladium (0) (241mg, 208μmol) suspension in THF (10ml) is heated at 110 DEG C for 15min via microwave irradiation.Then the crude product is poured over EtOAc and water.The water layer is extracted by EtOAc (x3), and the solvent is removed in vacuo.The crude product is purified by flash chromatography (heptane: 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] + .

[1896] Step 2: 3-[4-(2,4-difluorophenyl)phenyl]azetidine 4-methylbenzenesulfonic acid

[1897] The product was obtained analogously 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] + .

[1898] BB13

[1899] trans-3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]cyclobutanecarboxylic acid

[1900] Step 1: trans-methyl 3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]cyclobutanecarboxylate

[1901] To the ice-cold solution of 3-hydroxycyclobutanecarboxylic acid methyl ester (506mg, 3.89mmol, CAS RN 63485-51-8) in DMF (8.33mL) sodium hydride (55%, in mineral oil) (187mg, 4.28mmol) is added, and the mixture is stirred at this temperature for 30 minutes. At 0 ℃, a solution of 1-(bromomethyl)-2-fluoro-4-(trifluoromethyl) benzene (1g, 3.89mmol, CAS RN239087-07-1) in DMF (1.67mL) is added dropwise to the mixture. The slurries are continued to be stirred for 3 hours at room temperature. The reaction mixture is poured on saturated NH4Cl aqueous solution (300mL) and EtOAc (300mL), and each layer is separated. The water layer is extracted once with EtOAc (100mL). The organic layer is washed with water twice, through MgSO4 drying, filtered and evaporated, to obtain the required product, it is a colorless solid. MS (ESI): m / z = 307.1 [M+H] + . Used as is in the next step.

[1902] Step 2: trans-3-[[2-fluoro-4-(trifluoromethyl)phenyl]methoxy]cyclobutanecarboxylic acid

[1903] 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 onto water, and the pH was set to 2 using 1M HCl aqueous solution. 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 light yellow liquid (646 mg, 63.1%). MS (ESI): m / z=291.2 [MH] - .

[1904] BB 14

[1905] [3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]-[3-(4-tetrahydropyran-4...

Claims

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein: R 5 Selected from group 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 Selected from hydrogen, halogen, SF5, radical Aminosulfonyl, (C 1-6 -alkyl)2PO-C 1-6 -alkyl-, group 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 Selected from 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 or atoms to which they are attached, they form a 1-6 - a 3- to 14-membered heterocyclic ring substituted with an alkyl substituent; R 2a is selected from hydrogen and halogen; R 3 Selected from hydrogen and C 1-6 -alkyl; R 4 Selected from hydrogen, hydroxyl, amino, group Group Aminosulfonyl, carboxyl, hydroxy-C 1-6 -alkyl, C 1-6 -alkyl-SO2NH–, carbamoyl, C 1-6 -alkyl-NHC(O)–, (C 1-6 -alkyl)2NC(O)–, C 1-6 -alkyl-C(O)NH–, C 1-6 -alkoxy-C(O)NH– and C 1-6 -alkoxy-C(O)–; R 4a Selected from hydrogen and C 1-6 -alkyl; R 6 Selected from hydrogen, C 6-14 -Aryl and halo-C 6-14 - aryl; R 7 Selected from C 1-6 -alkyl, cyano-C 1-6 -alkyl and halo-C 1-6 -alkyl; R 8 Selected from hydrogen, halogen, cyano, hydroxyl, oxo, carboxyl, C 1-6 -Alkoxycarbonyl, C 1-6 -Alkyl, group Group Group 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 Selected from hydrogen, halogen, hydroxyl, C 1-6 -alkyl and halo-C 1-6 -alkyl; R 10 is selected from hydrogen and halogen; R 11 is selected from the group consisting of hydrogen, methyl, cyclopropylmethyl and phenyl; R 12 Selected from hydrogen, halogen, oxo, C 1-6 -alkyl, C 1-6 -alkoxycarbonyl and C 3-10 - cycloalkyl; R 13 Selected from hydrogen, C 1-6 -alkyl and halo-C 1-6 -alkyl; A is selected from C 6-14 -Aryl, C 3-10 - cycloalkyl, 5- to 6-membered heteroaryl, and 3- to 14-membered heterocyclyl; B is selected from the group consisting of azetidinyl, piperidinyl, piperazinyl, 2-azaspiro[3.3]heptyl, 2,6-diazaspiro[3.3]heptyl, 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]heptyl, the group and Group C is selected from phenyl, azetidinyl, pyrrolidinyl, piperidinyl, 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 selected from C 6-14 -Aryl, C 3-10 - cycloalkyl, 5- to 6-membered heteroaryl, and 3- to 14-membered heterocyclyl; E is selected from 5- to 14-membered heteroaryl, 3- to 14-membered heterocyclyl and C 3-10 - cycloalkyl; F is selected from C 3-10 - cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 14-membered heteroaryl; L is selected from a covalent bond, a carbonyl group, –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 L 1 Selected from covalent bonds, carbonyl groups, –CH2–, –CH2O–, –OCH2–, –NHCH2–, CH2NH–, –NR 11 –, –C(O)-NH-NH-C(O)-CH2–, –SO2–, and –O–; L 2 Selected from covalent bond and –SO2–; L 3 Selected from a covalent bond, a carbonyl group and –CH2–; X is selected from O and NH; Provided that when B is 2-azaspiro[3.3]heptyl or 2,6-diazaspiro[3.3]heptyl, L is not a covalent bond.

2. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 1, wherein the compound of formula (I) is a compound of formula (II), Where R 1 To R 4 , A, B and L as defined in claim 1; and p and q are each independently selected from 0 and 1.

3. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 1, wherein: R 5 Selected from group C 1-6 -alkyl-SO2–, C 1-6 -alkyl-SO2NH– and halo-C 1-6 - alkoxy; R 1 Selected from hydrogen, halogen, SF5, radical Aminosulfonyl, (C 1-6 -alkyl)2PO-C 1-6 -alkyl-, group 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 Selected from 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 one or more atoms to which they are attached, they form a 1-6 - a 3- to 14-membered heterocyclic ring substituted with an alkyl substituent; R 2a is selected from hydrogen and halogen; R 6 Selected from hydrogen, C 6-14 -Aryl and halo-C 6-14 - aryl; R 7 Selected from C 1-6 -alkyl, cyano-C 1-6 -alkyl and halo-C 1-6 -alkyl; R 8 Selected from hydrogen, halogen, cyano, hydroxyl, oxo, carboxyl, C 1-6 -Alkoxycarbonyl, C 1-6 -Alkyl, group Group Group 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 Selected from hydrogen, halogen, hydroxyl, C 1-6 -alkyl and halo-C 1-6 -alkyl; R 10 is selected from hydrogen and halogen; R 11 is selected from the group consisting of hydrogen, methyl, cyclopropylmethyl and phenyl; R 13 Selected from hydrogen, C 1-6 -alkyl and halo-C 1-6 -alkyl; A is selected from C 6-14 -Aryl, C 3-10 - cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 6-membered heteroaryl; D is selected from C 6-14 -Aryl, C 3-10 - cycloalkyl, 5- to 6-membered heteroaryl, and 3- to 14-membered heterocyclyl; F is selected from C 3-10 - cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 14-membered heteroaryl; L is selected from 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 L 1 Selected from covalent bonds, carbonyl groups, –CH2–, –CH2O–, –NHCH2–, CH2NH–, –NR 11 –, –C(O)-NH-NH-C(O)-CH2–, –SO2–, and –O–; L 3 is selected from the group consisting of a covalent bond, a carbonyl group, and –CH2–; and X is selected from O and NH.

4. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 3, wherein: R 5 For group R 1 Selected from halogen, C 1-6 -alkyl, halo-C 1-6 -Alkyl and group R 2 is selected from hydrogen, halogen and halo-C 1-6 -alkyl; R 2a is hydrogen; R 8 and R 9 are each independently selected from halogen and halo-C 1-6 -alkyl; R 10 is hydrogen; A is selected from C 6-14 -Aryl and C 3-10 - cycloalkyl; D is selected from C 6-14 -Aryl and C 3-10 - cycloalkyl; L is selected from the group consisting of a covalent bond, –O–, and –CH2O–; and L 1 It is a covalent bond.

5. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 4, wherein: R 5 For group R 1 Selected from fluorine, chlorine, tert-butyl, CHF2, CF3 and the group R 2 is selected from the group consisting of hydrogen, fluorine, chlorine and CF3; R 2a is hydrogen; R 8 and R 9 Each independently selected from fluorine, chlorine and CF3; R 10 is hydrogen; A is selected from phenyl and cyclopropyl; D is selected from phenyl and cyclopropyl; L is selected from the group consisting of a covalent bond, –O–, and –CH2O–; and L 1 It is a covalent bond.

6. A compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 5, wherein: B is selected from spiro[3.3]heptan-2-yl, azetidinyl and 7-azaspiro[3.5]nonan-7-yl; and R 3 For hydrogen.

7. A compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 6, wherein: R 4 Selected from group 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 It is a covalent bond.

8. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 7, wherein: R 4 Selected from group and carbamoyl; R 4a is hydrogen; R 12 is selected from hydrogen and oxo; C is pyrrolidinyl; E is selected from the group consisting of imidazolyl, pyrazolyl, triazolyl and oxazolidinyl; and L 2 It is a covalent bond.

9. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 1, wherein: R 5 Selected from group C 1-6 -alkyl-SO2–, C 1-6 -alkyl-SO2NH– and halo-C 1-6 - alkoxy; R 1 Selected from hydrogen, halogen, SF5, radical Aminosulfonyl, (C 1-6 -alkyl)2PO-C 1-6 -alkyl-, group 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 Selected from 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 one or more atoms to which they are attached, they form a 1-6 - a 3- to 14-membered heterocyclic ring substituted with an alkyl substituent; R 2a is selected from hydrogen and halogen; R 3 Selected from hydrogen and C 1-6 -alkyl; R 4 Selected from hydrogen, hydroxyl, amino, group Group Aminosulfonyl, carboxyl, hydroxy-C 1-6 -alkyl, C 1-6 -alkyl-SO2NH–, carbamoyl, C 1-6 -alkyl-NHC(O)–, (C 1-6 -alkyl)2NC(O)–, C 1-6 -alkyl-C(O)NH–, C 1-6 -alkoxy-C(O)NH– and C 1-6 -alkoxy-C(O)–; R 4a Selected from hydrogen and C 1-6 -alkyl; R 6 Selected from hydrogen, C 6-14 -Aryl and halo-C 6-14 - aryl; R 7 Selected from C 1-6 -alkyl, cyano-C 1-6 -alkyl and halo-C 1-6 -alkyl; R 8 Selected from hydrogen, halogen, cyano, hydroxyl, oxo, carboxyl, C 1-6 -Alkoxycarbonyl, C 1-6 -Alkyl, group Group 、Group 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 Selected from hydrogen, halogen, hydroxyl, C 1-6 -alkyl and halo-C 1-6 -alkyl; R 10 is selected from hydrogen and halogen; R 11 is selected from the group consisting of hydrogen, methyl, cyclopropylmethyl and phenyl; R 12 Selected from hydrogen, halogen, oxo, C 1-6 -alkyl, C 1-6 -alkoxycarbonyl and C 3-10 - cycloalkyl; R 13 Selected from hydrogen, C 1-6 -alkyl and halo-C 1-6 -alkyl; A is selected from C 6-14 -Aryl, C 3-10 - cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 6-membered heteroaryl; B is selected from the group consisting of azetidinyl, piperidinyl, piperazinyl, 2-azaspiro[3.3]heptyl, 2,6-diazaspiro[3.3]heptyl, 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]heptyl, the group and Group C is selected from phenyl, azetidinyl, pyrrolidinyl, piperidinyl, 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 selected from C 6-14 -Aryl, C 3-10 - cycloalkyl, 5- to 6-membered heteroaryl, and 3- to 14-membered heterocyclyl; E is selected from 5- to 14-membered heteroaryl, 3- to 14-membered heterocyclyl and C 3-10 - cycloalkyl; F is selected from C 3-10 - cycloalkyl, 3- to 14-membered heterocyclyl, and 5- to 14-membered heteroaryl; L is selected from 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 L 1 Selected from covalent bonds, carbonyl groups, –CH2–, –CH2O–, –NHCH2–, CH2NH–, –NR 11 –, –C(O)-NH-NH-C(O)-CH2–, –SO2–, and –O–; L 2 Selected from covalent bond and –SO2–; L 3 is selected from the group consisting of a covalent bond, a carbonyl group, and –CH2–; and X is selected from O and NH.

10. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 9, wherein: R 5 For group R 1 Selected from halogen, C 1-6 -alkyl, halo-C 1-6 -Alkyl and group R 2 is selected from hydrogen, halogen and halo-C 1-6 -alkyl; R 2a is hydrogen; R 3 is hydrogen; R 4 Selected from group and carbamoyl; R 4a is hydrogen; R 8 and R 9 are each independently selected from halogen and halo-C 1-6 -alkyl; R 10 is hydrogen; R 12 is selected from hydrogen and oxo; A is selected from 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 selected from 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 –CH2O–; L 1 is a covalent bond; and L 2 It is a covalent bond.

11. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 10, wherein: R 5 For group R 1 Selected from fluorine, chlorine, tert-butyl, CHF2, CF3 and the group R 2 is selected from the group consisting of hydrogen, fluorine, chlorine and CF3; R 2a is hydrogen; R 3 is hydrogen; R 4 Selected from group and carbamoyl; R 4a is hydrogen; R 8 and R 9 Each independently selected from fluorine, chlorine 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 the group consisting of imidazolyl, pyrazolyl, triazolyl and oxazolidinyl; L is selected from a covalent bond, –O– and –CH2O–; L 1 is a covalent bond; and L 2 It is a covalent bond.

12. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 1, which is selected from: [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-piperidinyl]-[3-(4-methyl-1H-pyrazol-5-yl)azetidin-1-yl]methanone; [4-[(4-chloro-2-fluoro-phenoxy)methyl]-1-piperidinyl]-[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-piperidinyl]methanone; [6-(2-Chloro-4-fluoro-phenoxy)-2-azaspiro[3.3]heptane-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-piperidinyl]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-λ 6 -thio)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; 5-[1-[3-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonyl]pyrrolidin-3-yl]-1H-pyrazole-4-carboxylic acid ethyl ester; 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]heptane-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-piperidinyl]-[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-(Oxetane-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-piperidinyl]-[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-piperidinyl]-[3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; (-)- or (+)-[4-[bis(4-fluorophenyl)methyl]-1-piperidinyl]-[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-λ 6 -thio)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-piperidinyl]-[(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; (-)-[4-[(2-chloro-4-fluoro-phenoxy)methyl]-1-piperidinyl]-[(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-piperidinyl]-[(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; (-)- or (+)-[4-[[2-chloro-4-(trifluoromethyl)phenyl]methoxy]-1-piperidinyl]-[(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-pyridinyl]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]heptane-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-pyridinyl]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]heptane-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]heptane-2-yl]methanone; [(3R)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridinyl]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]heptane-2-yl]methanone; [3-(Tetrazol-1-yl)pyrrolidin-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridinyl]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-pyridinyl]azetidin-1-yl]methanone; (-)- or (+)-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridinyl]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-(tetrazolyl-1-yl)pyrrolidin-1-yl]-[6-[6-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.3]heptane-2-yl]methanone; (-)- or (+)-[3-(tetrazolyl-1-yl)pyrrolidin-1-yl]-[6-[6-(trifluoromethyl)pyrazin-2-yl]oxy-2-azaspiro[3.3]heptane-2-yl]methanone; (+)- or (-)-[3-(tetrazol-1-yl)pyrrolidin-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridinyl]azetidin-1-yl]methanone; (-)- or (+)-[3-(tetrazol-1-yl)pyrrolidin-1-yl]-[3-[6-[4-(trifluoromethoxy)phenoxy]-3-pyridinyl]azetidin-1-yl]methanone; [(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[2-(3,3,3-trifluoropropoxy)spiro[3.3]heptane-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]heptane-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-pyridinyl]azetidin-1-yl]methanone; [(3R)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]-[3-[6-[3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridinyl]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]heptane-6-yl]methanone; [2-[[1-(Difluoromethyl)cyclopropyl]methoxy]spiro[3.3]heptane-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]heptane-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-pyridinyl]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-pyridinyl]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-pyridinyl)-methyl-amino]-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[6-[(5-ethyl-2-pyridinyl)-methyl-amino]-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[6-[(5-Cyclopropyl-2-pyridinyl)-methyl-amino]-3-pyridinyl]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-pyridinyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[6-(4-isopropyl-N-methyl-anilino)-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[6-[(3-ethyl-2-pyridinyl)-methyl-amino]-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[6-[N-(Cyclopropylmethyl)anilino]-3-pyridinyl]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-pyridinyl]azetidin-1-yl]-[3-(1H-tetrazolyl-5-yl)pyrrolidin-1-yl]methanone; [3-(1H-tetrazolyl-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]heptane-6-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [2-[4-Fluoro-2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptane-6-yl]-[(3S)-3-(1H-triazol-5-yl)pyrrolidin-1-yl]methanone; [2-(2,2-dimethylpropylsulfonyl)-2,6-diazaspiro[3.3]heptane-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]heptane-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]heptane-6-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [3-[6-[N-(Cyclopropylmethyl)anilino]-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(1H-tetrazolyl-5-yl)pyrrolidin-1-yl]methanone; [3-[6-[N-(Cyclopropylmethyl)anilino]-3-pyridinyl]azetidin-1-yl]-[(3R)-3-(1H-tetrazolyl-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-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(4-fluorophenoxy)phenyl]azetidin-1-yl]-[(3R)-3-(1H-tetrazolyl-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-tetrazolyl-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]heptane-2-yl]methanone; [(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]-[6-[[1-(trifluoromethyl)cyclopropyl]methoxy]-2-azaspiro[3.3]heptane-2-yl]methanone; (3S)-1-[3-[6-[N-(cyclopropylmethyl)anilino]-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3R)-1-[3-[6-[N-(cyclopropylmethyl)anilino]-3-pyridinyl]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-tetrazolyl-5-yl)pyrrolidin-1-yl]methanone; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[(3S)-3-(1H-tetrazolyl-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-pyridinyl]methoxy]azetidin-1-yl]methanone; [3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[[5-(trifluoromethyl)-3-pyridinyl]methoxy]azetidin-1-yl]methanone; [3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[6-[[5-(trifluoromethyl)-3-pyridinyl]oxy]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-chloro-3-pyridinyl)oxy]-2-azaspiro[3.3]heptan-2-yl]-[3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [6-[(6-chloro-3-pyridinyl)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-(phenylsulfonyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3R)-1-[3-[4-(phenylsulfonyl)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-pyridinyl]oxy]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[6-[[5-(trifluoromethyl)-2-pyridinyl]methyl]-2,6-diazaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[[5-(trifluoromethyl)-3-pyridinyl]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]heptane-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]heptane-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-pyridinyl]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-pyridinyl]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-pyridinyl]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]heptane-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]heptane-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; 2,2-dimethyl-3-[3-[1-[(3R)-3-(tetrazol-1-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]oxyphenyl]propanoic acid methyl ester; [3-[6-(2-chlorophenoxy)-3-pyridinyl]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-(tetrazolyl-1-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]cyclopropanecarbonitrile; [3-[4-(4-cyclopropylpyrimidin-2-yl)oxyphenyl]azetidin-1-yl]-[(3R)-3-(tetrazolyl-1-yl)pyrrolidin-1-yl]methanone; 1-[4-[1-[(3S)-3-(tetrazolyl-1-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]phenyl]cyclopropanecarbonitrile; 2,2-dimethyl-3-[3-[1-[(3S)-3-(tetrazol-1-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]oxyphenyl]propanoic acid methyl ester; [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]heptane-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]heptane-2-yl]-[(3S)-3-(1,2,4-triazol-4-yl)pyrrolidin-1-yl]methanone; [6-[(4,4-difluoro-1-piperidinyl)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]heptane-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-pyridinyl]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-pyridinyl]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]heptane-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]heptane-6-yl]methanone; N-methyl-2-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2,6-diazaspiro[3.3]heptane-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]heptane-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-pyridinyl]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]heptane-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-pyridinyl]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-pyridinyl]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]heptane-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-(tetrazolyl-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; 2-methyl-2-[3-[1-[(3S)-3-(tetrazol-1-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]oxyphenyl]propanoic acid methyl ester; [2-[4-Fluoro-2-(trifluoromethyl)phenyl]sulfonyl-2,6-diazaspiro[3.3]heptane-6-yl]-[(3S)-3-(tetrazol-1-yl)pyrrolidin-1-yl]methanone; 2-methyl-2-[3-[1-[(3R)-3-(tetrazol-1-yl)pyrrolidine-1-carbonyl]azetidin-3-yl]oxyphenyl]propanoic acid methyl ester; [(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]heptane-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]heptane-6-yl]-[(3R)-3-(tetrazolyl-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-pyridinyl)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]hexyl]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]heptane-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-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[5-(2,4-dichlorophenyl)-2-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[4-(5-chloro-3-methylsulfonyl-2-pyridinyl)phenyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[6-(2-chloro-4-methylsulfonyl-phenyl)-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[6-(4-chloro-2-methylsulfonyl-phenyl)-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(6-chloro-4-methylsulfonyl-3-pyridinyl)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-pyridinyl)methyl]-2-azaspiro[3.3]heptane-2-yl]-[(3S)-3-(tetrazolyl-1-yl)pyrrolidin-1-yl]methanone; [(3S)-3-(Tetrazol-1-yl)pyrrolidin-1-yl]-[6-[[6-(trifluoromethyl)-3-pyridinyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-fluoro-3-pyridinyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3S)-3-(tetrazolyl-1-yl)pyrrolidin-1-yl]methanone; [6-[(3,5-difluoro-2-pyridinyl)methyl]-2-azaspiro[3.3]heptane-2-yl]-[(3R)-3-(tetrazolyl-1-yl)pyrrolidin-1-yl]methanone; [(3R)-3-(Tetrazol-1-yl)pyrrolidin-1-yl]-[6-[[6-(trifluoromethyl)-3-pyridinyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[(5-fluoro-3-pyridinyl)methyl]-2-azaspiro[3.3]heptan-2-yl]-[(3R)-3-(tetrazolyl-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]heptane-6-yl]-2-(trifluoromethyl)benzenesulfonamide; N-[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptane-6-yl]-3-(trifluoromethyl)benzenesulfonamide; N-[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptane-6-yl]-4-(trifluoromethyl)benzenesulfonamide; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[5-(trifluoromethyl)-2-pyridinyl]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-pyridinyl]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-thiazin-4-yl)-3-pyridinyl]azetidin-1-yl]-[3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[5-(4-chloro-2-methylsulfonyl-phenyl)-2-pyridinyl]azetidin-1-yl]-[(3R)-3-hydroxypyrrolidin-1-yl]methanone; [3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[6-[[6-(trifluoromethyl)-3-pyridinyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; 1-[6-[[6-(Trifluoromethyl)-3-pyridinyl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-sulfonamide; 1-[6-[[6-(Trifluoromethyl)-3-pyridinyl]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]heptane-2-yl]methanone; [(3S)-3-(Tetrazol-1-yl)pyrrolidin-1-yl]-[6-[2-(trifluoromethyl)pyrimidin-5-yl]-2-azaspiro[3.3]heptane-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-pyridinyl]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]heptane-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-pyridinyl]azetidin-1-yl]methanone; (3S)-1-[3-[6-[[1-(trifluoromethyl)cyclopropyl]methylamino]-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; 4-Fluoro-N-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-4-piperidinyl]benzenesulfonamide; N-[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-4-piperidinyl]-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-piperidinyl]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-piperidinyl]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-piperidinyl]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]heptane-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-pyridinyl]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-pyridinyl]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-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; rac-(3S)-1-[3-[6-[3-hydroxy-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridinyl]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-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[6-[(3S)-3-hydroxy-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridinyl]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-pyridinyl]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-pyridinyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[6-(4-chloro-2-methylsulfonyl-phenoxy)-3-pyridinyl]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-pyridinyl]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]heptane-2-yl]-[(3S)-3-(tetrazolyl-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-pyridinyl]azetidin-1-yl]methanone; (3S)-1-[3-[6-(2-azaspiro[3.4]octan-2-yl)-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; 1-[3-[6-(2-azaspiro[3.4]octan-2-yl)-3-pyridinyl]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-pyridinyl]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-pyridinyl]-1,2,4-oxadiazol-3-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[5-[3-(trifluoromethyl)-1-bicyclo[1.1.1]pentyl]-1,2,4-oxadiazol-3-yl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; rac-(3S)-1-[3-[6-[3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridinyl]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]heptane-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-pyridinyl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; [3-[4-(4-chloro-2-methylsulfonyl-phenyl)phenyl]azetidin-1-yl]-[3-(methylsulfonimide)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]pentyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [3-[3-[5-(2,2-dimethylpropyl)-1,3,4-oxadiazol-2-yl]-1-bicyclo[1.1.1]pentyl]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-pyridinyl]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-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[6-(5-oxa-2-azaspiro[3.4]octan-2-yl)-3-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; [7-[[6-(Difluoromethoxy)-3-pyridinyl]methyl]-2-azaspiro[3.5]nonan-2-yl]-[(3S)-3-(tetrazolyl-1-yl)pyrrolidin-1-yl]methanone; [6-[(2,4-difluorophenyl)methyl]-2-azaspiro[3.3]heptane-2-yl]-[(3S)-3-(tetrazolyl-1-yl)pyrrolidin-1-yl]methanone; [6-[[2-Fluoro-4-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptane-2-yl]-[(3S)-3-(tetrazolyl-1-yl)pyrrolidin-1-yl]methanone; [6-[[4-Fluoro-2-(trifluoromethyl)phenyl]methyl]-2-azaspiro[3.3]heptane-2-yl]-[(3S)-3-(tetrazolyl-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-pyridinyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[6-[(3S)-3-(trifluoromethyl)pyrrolidin-1-yl]-3-pyridinyl]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-pyridinyl]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-pyridinyl]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-pyridinyl)methyl]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[(5-chloro-2-pyridinyl)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-pyridinyl]methyl]-2-azaspiro[3.5]nonane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[[6-(difluoromethoxy)-3-pyridinyl]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]heptane-2-yl]-[(3S)-3-(tetrazolyl-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]heptane-2-yl]-[(3S)-3-(triazol-1-yl)pyrrolidin-1-yl]methanone; [3-[6-(2-chlorophenoxy)-3-pyridinyl]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]heptane-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]heptane-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-pyridinyl]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-pyridinyl]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-pyridinyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; rac-(3S)-1-[6-[[6-(trifluoromethyl)-3-pyridinyl]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-pyridinyl]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-pyridinyl)-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-pyridinyl]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-pyridinyl]azetidin-1-yl]methanone; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[6-[3-(trifluoromethyl)azetidin-1-yl]-3-pyridinyl]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-pyridinyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [7-[(5-Fluoro-2-pyridinyl)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-pyridinyl)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-pyridinyl]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-pyridinyl]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-pyridinyl]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-pyridinyl]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-pyridinyl]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]pentyl]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]pentyl]azetidin-1-yl]methanone; [3-[3-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-1-bicyclo[1.1.1]pentyl]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]pentyl]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-pyridinyl]methyl]-2-azaspiro[3.3]heptane-2-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[7-[[5-(trifluoromethyl)-2-pyridinyl]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]pentyl]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]pentyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; (3S)-1-[3-[3-[[[1-(trifluoromethyl)cyclopropyl]amino]methyl]-1-bicyclo[1.1.1]pentyl]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]pentyl]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-pyridinyl)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]pentyl]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-pyridinyl]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-pyridinyl]methyl]-2-azaspiro[3.5]nonan-2-yl]methanone; [3-[6-(2-chlorophenoxy)-3-pyridinyl]azetidin-1-yl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [6-[(3,5-difluoro-2-pyridinyl)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]heptane-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-pyridinyl]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]heptane-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-pyridinyl]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-pyridinyl)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]heptane-6-yl]methyl]-5-(trifluoromethyl)benzonitrile; 4-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptane-6-yl]methyl]-2-(trifluoromethyl)benzonitrile; [(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[[6-(trifluoromethoxy)-3-pyridinyl]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]heptane-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-pyridinyl]methyl]-1-bicyclo[1.1.1]pentyl]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]heptane-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-pyridinyl)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-pyridinyl]methyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-Fluoro-5-(trifluoromethyl)-2-pyridinyl]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-pyridinyl]methyl]-2,7-diazaspiro[3.4]octan-2-yl]methanone; [7-[(5-chloro-2-pyridinyl)methyl]-2-azaspiro[3.5]nonan-2-yl]-[3-(1H-1,2,4-triazol-5-yl)azetidin-1-yl]methanone; [7-[[6-(Difluoromethoxy)-3-pyridinyl]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-piperidinyl]-[(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-piperidinyl]-[(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]pentyl]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]pentyl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [4-[[2-Fluoro-4-(trifluoromethoxy)phenyl]methoxy]-1-piperidinyl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [4-[[2-Fluoro-4-(trifluoromethyl)phenyl]methoxy]-1-piperidinyl]-[(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; 5-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptane-6-yl]methyl]-2-(trifluoromethoxy)benzoic acid methyl ester; [4-[[2-Methylsulfonyl-4-(trifluoromethyl)phenoxy]methyl]-1-piperidinyl]-[(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-pyridinyl]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]heptane-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]heptane-6-yl]methyl]-2-(trifluoromethoxy)benzamide; [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[5-[1-(trifluoromethyl)cyclopropyl]-2-pyridinyl]azetidin-1-yl]methanone; [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[3-[[6-(trifluoromethyl)-3-pyridinyl]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-piperidinyl]-[(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]heptane-6-yl]methyl]-2-(trifluoromethoxy)benzamide; [rac-(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[3-[4-(trifluoromethylsulfonimide)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]pentyl]azetidin-1-yl]methanone; 4-[[2-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-2-azaspiro[3.3]heptane-6-yl]methyl]-2-(trifluoromethoxy)benzoic acid methyl ester; [4-[[2-Methylsulfonyl-4-(trifluoromethoxy)phenoxy]methyl]-1-piperidinyl]-[(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-pyridinyl]methoxymethyl]-1-piperidinyl]methanone; [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[4-[[6-(trifluoromethyl)-3-pyridinyl]oxymethyl]-1-piperidinyl]methanone; [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[4-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]-1-piperidinyl]methanone; [4-[[4-Fluoro-3-(trifluoromethyl)phenoxy]methyl]-1-piperidinyl]-[(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]methanone; [4-[[3-Fluoro-5-(trifluoromethyl)phenoxy]methyl]-1-piperidinyl]-[(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-pyridinyl]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]pentyl]acetyl]cyclopropanecarboxyhydrazide; [4-[[2-Methylsulfonyl-4-(trifluoromethoxy)phenyl]methoxy]-1-piperidinyl]-[(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]pentyl]azetidine-1-carbonyl]pyrrolidine-3-carboxamide; 2-methoxy-4-[[1-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidine-1-carbonyl]-4-piperidinyl]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-piperidinyl]oxymethyl]benzamide; (3S)-1-[3-[3-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-1-bicyclo[1.1.1]pentyl]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]heptane-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]pentyl]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]pentyl]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-(trifluoromethylsulfonimide)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]sulfimidoyl]-2-azaspiro[3.3]heptan-2-yl]methanone; [6-[[3-Fluoro-5-(trifluoromethylsulfonamidoyl)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]sulfonimide]-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]sulfonimide]-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-8λ6-thia-9-azatricyclo[8.4.0.02,7]tetradec-1(10),2(7),3,5,8,11,13-hepten-12-yl]azetidin-1-yl]-[(3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]methanone; [3-[(8S)-8-methyl-8-oxo-8λ6-thia-9-azatricyclo[8.4.0.02,7]tetradec-1(10),2(7),3,5,8,11,13-hepten-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]pentyl]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]pentyl]azetidin-1-yl]methanone; [(3S)-3-(4H-1,2,4-triazol-3-yl)pyrrolidin-1-yl]-[4-[[5-(trifluoromethyl)-2-pyridinyl]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]heptane-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]pentyl]benzonitrile; [3-[3-(3-methyl-1H-pyrazol-5-yl)-1-bicyclo[1.1.1]pentyl]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]pentyl]azetidin-1-yl]methanone; [3-[3-(4-chloro-2-methylsulfonyl-phenyl)-1-bicyclo[1.1.1]pentyl]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]heptane-6-yl]oxy]-2-(trifluoromethyl)benzonitrile; [6-[(5-fluoro-2-pyridinyl)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]pentyl]methanone; (3S)-3-(1H-1,2,4-triazol-5-yl)pyrrolidin-1-yl]-[6-[4-(trifluoromethylsulfonimidoyl)phenoxy]-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]heptane-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-pyridinyl]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]heptane-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-(trifluoromethylsulfonamidoyl)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.

13. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 12, which is selected from: [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.

14. A method for producing a compound of formula (IA) or (IB) according to any one of claims 1 to 13, the method comprising: (a) an amine of formula 2, wherein p, q and R 4 As defined in any one of claims 1 to 13, with carboxylic acid 3a, where L, A, B and R 1 To R 3 As defined in any one of claims 1 to 13, In the presence of a coupling reagent selected from CDI, DCC, HATU, HBTU, HOBT, TBTU, T3P and Mukaiyama reagent, and optionally in the presence of a base selected from TEA, DIPEA (Huenig's base) and DMAP, to form the compound of formula (IB), wherein A, B, L, p, q and R 1 To R 4 As defined in any one of claims 1 to 13 or (b) an amine of formula 2, wherein p, q and R 4 As defined in any one of claims 1 to 13, With carboxylic acid chloride 3b, where L, A, B and R 1 To R 3 As defined in any one of claims 1 to 13, In the presence of a base selected from TEA, Huenig's base, pyridine, DMAP and lithium bis(trimethylsilyl)amide, to form the compound of formula (IB), wherein A, B, L, p, q and R 1 To R 4 As defined in any one of claims 1 to 13; or (c) making a first amine of formula 1, wherein A, B, L and R 1 To R 3 As defined in any one of claims 1 to 13, and a second amine 2, wherein X, Y and Z are as defined in any one of claims 1 to 13, reacting in the presence of sodium bicarbonate and a urea-forming agent selected from bis(trichloromethyl) carbonate, phosgene, trichloromethyl chloroformate, (4-nitrophenyl) carbonate and 1,1'-carbonyldiimidazole, To form the compound of formula (IA), wherein A, B, L, p, q and R 1 To R 4 As defined in any one of claims 1 to 13 15. A compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 13, produced according to the method of claim 14.

16. A compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 13 and 15 for use as a therapeutically active substance.

17. A pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 13 and 15, and a therapeutically inert carrier.

18. Use of a compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 13 and 15, or a pharmaceutical composition according to claim 17 for treating or preventing neuroinflammation, neurodegenerative diseases, pain, cancer, mental disorders and / or inflammatory bowel disease in mammals.

19. Use of a compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 13 and 15, or a pharmaceutical composition according to claim 17, 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 carcinoma, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, pain-related cramps, abdominal pain, abdominal pain associated with irritable bowel syndrome and / or visceral pain in a mammal.

20. A compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 13 and 15, or a pharmaceutical composition according to claim 17, for use in treating or preventing neuroinflammation, neurodegenerative diseases, pain, cancer, mental disorders and / or inflammatory bowel disease in mammals.

21. A compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 13 and 15, or a pharmaceutical composition according to claim 17, for use in 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 carcinoma, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, pain-related cramps, abdominal pain, abdominal pain associated with irritable bowel syndrome and / or visceral pain in a mammal.

22. Use of a compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 13 and 15 for preparing a medicament for treating or preventing neuroinflammation, neurodegenerative diseases, pain, cancer, mental disorders and / or inflammatory bowel disease in mammals.

23. Use of a compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 13 and 15 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 carcinoma, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, pain-related cramps, abdominal pain, abdominal pain associated with irritable bowel syndrome and / or visceral pain in a mammal.

24. A method, wherein the method is used to treat or prevent neuroinflammation, neurodegenerative disease, pain, cancer, mental disorder or inflammatory bowel disease in a mammal, The method comprises administering to the mammal an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 13 and 15, or a pharmaceutical composition according to claim 17.

25. A method, wherein the method is used to treat or prevent multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, neurotoxicity, stroke, epilepsy, anxiety, migraine, depression, hepatocellular carcinoma, colon carcinoma, ovarian cancer, neuropathic pain, chemotherapy-induced neuropathy, acute pain, chronic pain, pain-related spasticity, abdominal pain, abdominal pain associated with irritable bowel syndrome, or visceral pain in a mammal, The method comprises administering to the mammal an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 13 and 15, or a pharmaceutical composition according to claim 17.

26. The invention as hereinbefore described.

Images