Sarm1 inhibitors

Abstract

The invention provides compounds having the general formula (I) wherein X, Y, Z, U, V, and R1 to R7 are as described herein, compositions including the compounds, processes of manufacturing the compounds and methods of using the5 compounds in the treatment or prevention of diseases that are associated with SARM1.

Description

[0001] F. Hoffmann-La Roche AG, CH-4070 Basel, Switzerland Case: P38650 SARM1 INHIBITORS Field of the Invention The present invention relates to organic compounds useful for therapy or prophylaxis in a mammal, and in particular to Sterile Alpha And TIR Motif Containing 1 (SARM1) inhibitors for the treatment or prevention of amyotrophic lateral sclerosis, spinal muscular atrophy, chemotherapy induced peripheral neuropathy, diabetes induced peripheral neuropathy, multiple sclerosis, Parkinson's disease, glaucoma, stroke, traumatic brain injury, and Charcot-Marie- Tooth disease. Background of the Invention Axonal degeneration is a central driver of disability and disease progression in neurodegenerative and neurological disorders including multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Parkinson’s disease, Alzheimer’s disease and peripheral neuropathies. Due to their high energy demands in order to propagate action potentials and ensure protein transport over sometimes meter-long distances, axons are particularly sensitive to metabolic stress following for example mitochondrial disruption or microtubule disassembly. Instead of being a passive dying process however, the resulting axonal degeneration is now understood to involve key molecular components and steps. Programmed axonal degeneration, also known as Wallerian degeneration, is a key molecular mechanism driving axonal loss. As an early pathological feature of numerous neurological conditions associated with an increasing societal and economic burden, therapeutic approaches to target the prevention of axonal degeneration therefore hold significant treatment potential. Summary of the Invention In a first aspect, the present invention provides compounds of formula (I) CNE / 14.06.2024 wherein X, Y, Z, U, V, and R1to R7are as defined herein. In further aspects, the invention provides compositions including the compounds of formula (I), processes of manufacturing the compounds of formula (I) and methods of using the compounds of formula (I). Detailed Description of the Invention Definitions 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 of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and / or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and / or steps are mutually exclusive. The invention is not restricted to the details of any foregoing embodiments. The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed. The term “alkyl” refers to a mono- or multivalent, e.g., a mono- or bivalent, linear or branched saturated hydrocarbon group of 1 to 6 carbon atoms (“C1-6-alkyl”), e.g., 1, 2, 3, 4, 5, or 6 carbon atoms. In some embodiments, the alkyl group contains 1 to 4 carbon atoms, e.g., 1, 2, 3, or 4 carbon atoms. In other embodiments, the alkoxy group contains 1 to 3 carbon atoms. Some non- limiting examples of alkyl include methyl, ethyl, propyl, 2-propyl (isopropyl), n-butyl, iso-butyl, sec-butyl, tert-butyl, and 2,2-dimethylpropyl. Particularly preferred, yet non-limiting examples of alkyl are methyl, tert-butyl, and 2,2-dimethylpropyl. The term “alkoxy” refers to an alkyl group, as previously defined, attached to the parent molecular moiety via an oxygen atom. Unless otherwise specified, the alkoxy group contains 1 to 6 carbon atoms (“C1-6-alkoxy”). In some embodiments, the alkoxy group contains 1 to 4 carbon atoms, e.g., 1, 2, 3, or 4 carbon atoms. In other embodiments, the alkoxy group contains 1 to 3 carbon atoms. Some non-limiting examples of alkoxy groups include methoxy, ethoxy, n- propoxy, isopropoxy, n-butoxy, isobutoxy and tert-butoxy. A particularly preferred, yet non- limiting example of alkoxy is methoxy. The term “haloalkoxy” refers to an alkoxy group, wherein at least one of the hydrogen atoms of the alkoxy group has been replaced by a halogen atom, preferably fluoro. Preferably, “haloalkoxy” refers to an alkoxy group wherein 1, 2 or 3 hydrogen atoms of the alkoxy group have been replaced by a halogen atom, most preferably fluoro. Prticularly preferred, yet non- limiting examples of haloalkoxy are trifluoromethoxy, 3,3,3-trifluoropropoxy, 2,2,2-trifluoro-1- methyl-ethoxy, and 3-fluoro-2-fluoro-propoxy. The term “alkoxyalkyl” refers to an alkyl group, wherein at least one of the hydrogen atoms of the alkyl group has been replaced by an alkoxy group. Preferably, “alkoxyalkyl” refers to an alkyl group wherein 1, 2 or 3 hydrogen atoms, most preferably 1 hydrogen atom of the alkyl group have been replaced by an alkoxy group. Some particularly preferred, yet non-limiting examples of alkoxyalkyl are 2-methoxy-2,2-dimethyl-ethyl, methoxymethyl, and 2- methoxyethyl. The term “haloalkoxyalkyl” refers to an alkyl group, wherein at least one of the hydrogen atoms of the alkyl group has been replaced by a haloalkoxy group. Preferably, “haloalkoxyalkyl” refers to an alkyl group wherein 1, 2 or 3 hydrogen atoms, most preferably 1 hydrogen atom of the alkyl group have been replaced by a haloalkoxy group. Particularly preferred, yet non-limiting examples of haloalkoxyalkyl are difluoromethoxymethyl and trifluoromethoxymethyl. The term “halogen” or “halo” refers to fluoro (F), chloro (Cl), bromo (Br), or iodo (I). Preferably, the term “halogen” or “halo” refers to fluoro (F), chloro (Cl) or bromo (Br). Particularly preferred, yet non-limiting examples of “halogen” or “halo” are fluoro (F) and chloro (Cl). The term “cyano” refers to a –CN (nitrile) group. The term “hydroxy” refers to an –OH group. The term “cycloalkyl” as used herein refers to a saturated monocyclic or bicyclic hydrocarbon group of 3 to 10 ring carbon atoms (“C3-10-cycloalkyl”). In some preferred embodiments, the cycloalkyl group is a monocyclic hydrocarbon group of 3 to 8 ring carbon atoms. “Bicyclic cycloalkyl” refers to cycloalkyl moieties consisting of two saturated carbocycles having two carbon atoms in common, i.e., the bridge separating the two rings is either a single bond or a chain of one or two ring atoms, and to spirocyclic moieties, i.e., the two rings are connected via one common ring atom. Preferably, the cycloalkyl group is a monocyclic hydrocarbon group of 3 to 6 ring carbon atoms, e.g., of 3, 4, 5 or 6 carbon atoms. Some non-limiting examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 1- bicyclo[1.1.1]pentanyl, norbornanyl, and 1-bicyclo[2.2.2]octanyl. Particularly preferred, yet non- limiting examples of cycloalkyl are cyclopropyl, bicyclo[1.1.1]pentanyl and cyclohexyl. The term "aryl" refers to a monocyclic, bicyclic, or tricyclic carbocyclic ring system having a total of 6 to 10 ring members (“C6-C10-aryl”), 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, yet non-limiting example of aryl is phenyl. The term “aroyl” refers to an aryl moiety that is bound to the parent moiety via a carbonyl group. A preferred, yet non-limiting example of aroyl is benzoyl. The term “heteroaroyl” refers to a heteroaryl moiety that is bound to the parent moiety via a carbonyl group. A preferred, yet non-limiting example of heteroaroyl is pyridine-3-carbonyl. The term "heteroaryl" refers to a mono- or multivalent, monocyclic, bicyclic or tricyclic, preferably bicyclic ring system having a total of 5 to 14 ring members, preferably, 5 to 12 ring members, for example 5 to 11, 5 to 10, 5 to 9, 5 to 8, 5 to 7 or 5 to 6 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 5-9 membered heteroaryl comprising 1, 2, 3 or 4 heteroatoms independently selected from O, S and N. Most preferably, “heteroaryl” refers to a 5- 6 membered heteroaryl comprising 1 to 2 heteroatoms independently selected from O and N. Some non-limiting examples of heteroaryl include pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, 1,3-benzoxazol-2-yl, 1,3-benzoxazol-4-yl, 1,3-benzoxazol-5-yl, 1,3-benzoxazol-6-yl, 1,3-benzoxazol-7-yl, 1H-indazol-3-yl, 1H-indazol-4-yl, oxadiazolyl (e.g.1,2,4-oxadiazol-3-yl, 1,3,4-oxadiazol-2-yl), pyrazolyl (e.g.1H-pyrazol-4-yl), triazolyl (e.g.1H-1,2,4-triazol-3-yl, 1H- triazol-4-yl, 2H-triazol-4-yl), and tetrazolyl (e.g.2H-tetrazol-5-yl). The term “heterocyclyl” as used herein refers to a saturated or partly unsaturated mono- or bicyclic, preferably monocyclic ring system of 3 to 14 ring atoms, e.g.3 to 13, 3 to 12, 3 to 11, 3 to 10, 3 to 9, 3 to 8, 3 to 7, 3 to 6 or 3 to 5 ring atoms, preferably 3 to 10 ring atoms, more preferably 3 to 10 ring atoms, most preferably 3 to 8 ring atoms, wherein 1, 2, or 3 of said ring atoms are heteroatoms selected from N, O and S, the remaining ring atoms being carbon. Preferably, 1 to 2 of said ring atoms are selected from N and O, the remaining ring atoms being carbon. “Bicyclic heterocyclyl” refers to heterocyclic moieties consisting of two cycles having two ring atoms in common, i.e., the bridge separating the two rings is either a single bond or a chain of one or two ring atoms, and to spirocyclic moieties, i.e., the two rings are connected via one common ring atom. Some non-limiting examples of monocyclic heterocyclyl groups include azetidin-3-yl, azetidin-2-yl, 2-azaspiro[3.3]heptan-2-yl, 2,6-diazaspiro[3.3]heptan-2-yl, 2- azaspiro[3.4]octan-2-yl, 5-oxa-2-azaspiro[3.4]octan-2-yl, pyrrolidinyl (e.g. pyrrolidin-1-yl), thiomorpholino, oxetan-3-yl, oxetan-2-yl, tetrahydrofuranyl (e.g. tetrahydrofuran-2-yl), tetrahydropyranyl (e.g. tetrahydropyran-2-yl), 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4- piperidinyl, piperazinyl (e.g. piperazin-1-yl), morpholino, morpholin-2-yl and morpholin-3-yl. The term “haloalkyl” refers to an alkyl group as defined herein, wherein at least one of the hydrogen atoms of the alkyl group has been replaced by a halogen atom, preferably fluoro. Preferably, “haloalkyl” refers to an alkyl group wherein 1, 2 or 3 hydrogen atoms of the alkyl group have been replaced by a halogen atom, most preferably fluoro. Particularly preferred, yet non-limiting examples of haloalkyl are trifluoromethyl, difluoromethyl, 1,1-difluoroethyl, 2,2- difluoroethyl, and 2,2,2-trifluoroethyl. The term “hydroxyalkyl” refers to an alkyl group, wherein at least one of the hydrogen atoms of the alkyl group has been replaced by a hydroxy group. Preferably, “hydroxyalkyl” refers to an alkyl group wherein 1, 2 or 3 hydrogen atoms, most preferably 1 hydrogen atom of the alkyl group have been replaced by a hydroxy group. Preferred, yet non-limiting examples of hydroxyalkyl are 2-hydroxy-1,1-dimethylethyl, 2-hydroxy-2-methyl-propyl, hydroxymethyl and hydroxyethyl (e.g.2-hydroxyethyl). The term "pharmaceutically acceptable salt" refers to those salts which retain the biological effectiveness and properties of the free bases or free acids, which are not biologically or otherwise undesirable. The salts are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, in particular hydrochloric acid, and organic acids such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p- toluenesulfonic acid, salicylic acid, N-acetylcystein and the like. In addition these salts may be prepared by addition of an inorganic base or an organic base to the free acid. Salts derived from an inorganic base include, but are not limited to, the sodium, potassium, lithium, ammonium, calcium, magnesium salts and the like. Salts derived from organic bases include, but are not limited to salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, lysine, arginine, N-ethylpiperidine, piperidine, polyimine resins and the like. The compounds of formula (I) can contain several asymmetric centers and can be present in the form of optically pure enantiomers, mixtures of enantiomers such as, for example, racemates, optically pure diastereioisomers, mixtures of diastereoisomers, diastereoisomeric racemates or mixtures of diastereoisomeric racemates. The abbreviation “SARM1” refers to Sterile Alpha and TIR Motif Containing 1. The term “treatment” as used herein includes: (1) inhibiting the state, disorder or condition (e.g. arresting, reducing or delaying the development of the disease, or a relapse thereof in case of maintenance treatment, of at least one clinical or subclinical symptom thereof); and / or (2) relieving the condition (i.e., causing regression of the state, disorder or condition or at least one of its clinical or subclinical symptoms). The benefit to a patient to be treated is either statistically significant or at least perceptible to the patient or to the physician. However, it will be appreciated that when a medicament is administered to a patient to treat a disease, the outcome may not always be effective treatment. The term “prophylaxis” as used herein includes: preventing or delaying the appearance of clinical symptoms of the state, disorder or condition developing in a mammal and especially a human that may be afflicted with or predisposed to the state, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disorder or condition. Axonal breakdown distal to the site of an injury is a key feature of programmed axonal degeneration or Wallerian degeneration and is characterized by mitochondrial disruption, loss of nicotinamide adenine dinucleotide (NAD+), increased intracellular calcium levels and axonal fragmentation (Conforti, L., et al., Nat. Rev. Neurosci., 2014, 15, 394–409). The central component of the programmed axonal degeneration mechanism is Sterile Alpha And TIR Motif Containing 1 (SARM1) (Osterloh, J.M., et al., Science, 2012, 337, 481-484). SARM1 is an NAD+ hydrolase that depletes levels of NAD+ by cleaving it into the metabolites: nicotinamide (NAM) and adenosine diphosphate ribose (ADPR) or cyclic ADPR. The resulting loss of NAD+, an essential metabolite involved in energy metabolism and axonal homeostasis (Hopkins, E.L., et al., 2021, Front. Mol. Biosci., 8:703532), and increase in cADPR, a modulator of intra-axonal calcium levels (Li, Y., et al., 2022, J. Cell Biol., 221, e202106080), contributes to the subsequent axonal degeneration process. Other molecular components of the Wallerian axonal degeneration pathway have been identified including axonal survival factors like nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2). Under normal conditions, axonal survival factors such as NMNAT2 are continuously turned over and replenished by anterograde transport along the axon from the cell body (Gilley, J. & Coleman, M.P., 2010, PLoS Biol., 8, e1000300). NMNAT2 maintains axonal energetics by catalyzing the formation of NAD+ from nicotinamide mononucleotide (NMN) and adenosine tri-phosphate (ATP). However during injury or disease, disruption of microtubule assembly or mitochondrial depolarization in axons leads to loss of NMNAT2 transport followed by NMNAT2 depletion. SARM1 is activated in turn by reduced NMNAT2 levels as a result of loss of NAD+, a negative SARM1 ligand, and accumulation of NMN, a positive SARM1 ligand (Figley, M.D., et al., 2021, Neuron, 109, 1118-1136). SARM1 is a multidomain protein consisting of an autoinhibitory ARM domain, tandem oligomerization SAM domains and a catalytic TIR domain. While originally thought to exist as a monomer in solution, recent high-resolution cryo-EM structures have revealed that SARM1 exists as an octamer with the ARM domains locking the TIR domains in an inactive conformation (Bratkowski, M., et al., 2020, Cell Rep., 32, 107999). This was followed by identification of an allosteric site in which both NMN and NAD+ can bind (Jiang, Y., et al., 2020, Nature, 588, 658-663; Figley, M.D., et al., 2021, Neuron, 109, 1118-1136). The increase in NMN / NAD+ during axonal injury and the higher affinity of NMN for SARM1 results in replacement of NAD+ in the allosteric pocket, releasing the ARM domains and allowing for TIR domain catalytic activity. Both in vitro and in vivo studies of SARM1 loss-of-function have highlighted the central role of SARM1 in programmed axonal degeneration. SARM1 genetic knockout has been shown to protect axons in both human and rodent neuronal cultures following physical (axotomy) or chemical injury, for example due to chemotherapeutic drugs such as vincristine (Osterloh, J.M., et al., Science, 2012, 337, 481-484; Chen, Y., et al., 2021, Exp. Neurol., 339, 113636). In vivo, deletion of SARM1 prevents nerve fiber loss and restores normal pain sensitivity in models of chemotherapy-induced peripheral neuropathy (Geisler, S., et al., 2016, Brain, 139, 3092-3108) and diabetic peripheral neuropathy (Cheng, Y., et al., 2019, Diabetes, 68, 2120-2130). SARM1 deletion also attenuates axonal degeneration in pre-clinical models of ALS (White, M.A., et al., Acta Neuropathol. Commun., 7, 166) and MS (Viar, K., et al., 2020, PLoS One, 15, e0235110). In models of eye disorders, SARM1 deficiency has been found to block loss of axons of retinal ganglion cells in glaucoma models (Finnegan, L.K., et al., 2022, Int. J. Mol. Sci., 23, 1606) and of photoreceptors in retinitis pigmentosa models (Ozaki, E., et al., 2020, Life Sci. Alliance., 3, e201900618). These combined studies underscore the therapeutic potential of blocking SARM1 activity to ameliorate various neurological disorders associated with axonal loss. Compounds of the Invention In a first aspect, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein: X, Y and Z are each selected from CRZand N, provided that at most two of X, Y and Z are N; U is selected from O, S, and NRU; V is a covalent bond or C(RV)2; A is selected from 3- to 14-membered heterocyclyl, 5- to 14-membered heteroaryl, C6- C10-aryl and C3-C10-cycloalkyl; L is selected from a covalent bond, –CH2–, and –NRL–; RLis selected from hydrogen and C1-C6-alkyl; RUis selected from hydrogen, C1-C6-alkyl and cyano; each RVis independently selected from hydrogen, C1-C6-alkyl and halo-C1-C6-alkyl; RZis selected from hydrogen and C1-C6-alkyl; R1is selected from hydrogen, halogen, cyano, C1-C6-alkyl, C2-C6-alkenyl, C2-C6- alkynyl, halo-C1-C6-alkyl, hydroxy-C1-C6-alkyl, C1-C6-alkoxy, halo-C1-C6-alkoxy, and a group R1ais selected from hydrogen, halogen, C1-C6-alkyl, and halo-C1-C6-alkyl; R2aand R2bare each independently selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, C1-C6-alkoxy, halo-C1-C6-alkoxy, C1-C6-alkyl-NH-C1-C6-alkyl-, C3-C10-cycloalkyl, C3-C10-cycloalkyl-C1-C6-alkyl, C6-C10-aryl, C6-C10-aryl-C1-C6-alkyl, and R2c-O-C1- C6-alkyl; wherein each C6-C10-aryl and C3-C10-cycloalkyl is optionally substituted with 1-2 halogen substituents or R2aand R2b, taken together with the carbon atom to which they are attached, form a C3- C10-cycloalkyl; R2cis selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, and C6-C10-aryl; wherein said C6-C10-aryl is optionally substituted with 1-2 halogen substituents; R3is selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, and C3-C10-cycloalkyl; R4aand R4bare each independently selected from hydrogen, halogen, hydroxy, C1-C6- alkyl, 5- to 14-membered heteroaryl, C6-C10-aryl, C6-C10-aroyl, 5- to 14-membered heteroaroyl; wherein said 5- to 14-membered heteroaryl, C6-C10-aryl, C6-C10-aroyl, 5- to 14-membered heteroaroyl are optionally substituted with 1-3 substituents independently selected from halogen and hydroxy-C1-C6-alkyl; or R4aand R4b, taken together with the carbon atom to which they are attached, form a C3- C10-cycloalkyl or a 3- to 14-membered heterocyclyl, wherein said C3-C10-cycloalkyl and 3- to 14-membered heterocyclyl are optionally substituted with 1-3 halogen substituents; or R4aand R7, taken together with the carbon atoms to which they are attached, form a C3- C10-cycloalkyl; R5aand R5bare each independently selected from hydrogen and C1-C6-alkyl; or R5aand R5b, taken together with the carbon atom to which they are attached, form a C3- C10-cycloalkyl or oxo; R6aand R6bare each independently selected from hydrogen, 5- to 14-membered heteroaryl, and C6-C10-aryl; wherein said 5- to 14-membered heteroaryl, and C6-C10-aryl are optionally substituted with 1-3 substituents independently selected from halogen, C1- C6-alkyl, halo-C1-C6-alkyl, C3-C10-cycloalkyl, and 5- to 14-membered heteroaryl; and R7is selected hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, and 5- to 14-membered heteroaryl. In one embodiment, the present invention provides a compound of Formula (I) as described herein, wherein: X, Y and Z are each selected from CH and N, provided that at most two of X, Y and Z are N; U is selected from O, S, and NRU; V is a covalent bond or C(RV)2; A is selected from 3- to 14-membered heterocyclyl, 5- to 14-membered heteroaryl, C6- C10-aryl and C3-C10-cycloalkyl; L is selected from a covalent bond and –NRL–; RLis selected from hydrogen and C1-C6-alkyl; RUis selected from hydrogen, C1-C6-alkyl and cyano; each RVis independently selected from hydrogen, C1-C6-alkyl and halo-C1-C6-alkyl; R1is selected from hydrogen, halogen, cyano, C1-C6-alkyl, halo-C1-C6-alkyl, hydroxy- C1-C6-alkyl, C1-C6-alkoxy, halo-C1-C6-alkoxy, and a group ; R1ais selected from hydrogen, halogen, and C1-C6-alkyl; R2aand R2bare each independently selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, C1-C6-alkoxy, halo-C1-C6-alkoxy, C1-C6-alkyl-NH-C1-C6-alkyl-, C3-C10-cycloalkyl, and R2c-O-C1-C6-alkyl; or R2aand R2b, taken together with the carbon atom to which they are attached, form a C3- C10-cycloalkyl; R2cis selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, and C6-C10-aryl; R3is selected from hydrogen, C1-C6-alkyl, and C3-C10-cycloalkyl; R4aand R4bare each independently selected from hydrogen, halogen, hydroxy, C1-C6- alkyl, 5- to 14-membered heteroaryl, C6-C10-aryl, C6-C10-aroyl, 5- to 14-membered heteroaroyl; wherein said 5- to 14-membered heteroaryl, C6-C10-aryl, C6-C10-aroyl, 5- to 14-membered heteroaroyl are optionally substituted with 1-3 substituents independently selected from halogen and hydroxy-C1-C6-alkyl; or R4aand R4b, taken together with the carbon atom to which they are attached, form a C3- C10-cycloalkyl or a 3- to 14-membered heterocyclyl, wherein said C3-C10-cycloalkyl and 3- to 14-membered heterocyclyl are optionally substituted with 1-3 halogen substituents; or R4aand R7, taken together with the carbon atoms to which they are attached, form a C3- C10-cycloalkyl; R5aand R5bare each independently selected from hydrogen and C1-C6-alkyl; or R5aand R5b, taken together with the carbon atom to which they are attached, form a C3- C10-cycloalkyl; R6aand R6bare each independently selected from hydrogen, 5- to 14-membered heteroaryl, and C6-C10-aryl; wherein said 5- to 14-membered heteroaryl, and C6-C10-aryl are optionally substituted with 1-3 substituents independently selected from halogen, C1- C6-alkyl, halo-C1-C6-alkyl, C3-C10-cycloalkyl, and 5- to 14-membered heteroaryl; and R7is selected hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, and 5- to 14-membered heteroaryl. In a preferred embodiment, the present invention provides a compound of Formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula (I) is a compound of Formula (Ia) or a pharmaceutically acceptable salt thereof, wherein: X, Y and Z are each selected from CH and N, provided that at most two of X, Y and Z are N; R1is selected from hydrogen, halogen, cyano, C1-C6-alkyl, halo-C1-C6-alkyl, and C3- C10-cycloalkyl; R2aand R2bare each independently selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, C1-C6-alkoxy, halo-C1-C6-alkoxy, C1-C6-alkyl-NH-C1-C6-alkyl-, C1-C6-alkoxy-C1- C6-alkyl, and halo-C1-C6-alkoxy-C1-C6-alkyl; or R2aand R2b, taken together with the carbon atom to which they are attached, form a C3- C10-cycloalkyl; R3is selected from hydrogen, C1-C6-alkyl, and C3-C10-cycloalkyl; R4aand R4bare each independently selected from hydrogen, halogen, hydroxy, C1-C6- alkyl, 5- to 14-membered heteroaryl, C6-C10-aryl, C6-C10-aroyl, 5- to 14-membered heteroaroyl; wherein said 5- to 14-membered heteroaryl, C6-C10-aryl, C6-C10-aroyl, 5- to 14-membered heteroaroyl are optionally substituted with 1-3 substituents independently selected from halogen and hydroxy-C1-C6-alkyl; or R4aand R4b, taken together with the carbon atom to which they are attached, form a C3- C10-cycloalkyl or a 3- to 14-membered heterocyclyl, wherein said C3-C10-cycloalkyl and 3- to 14-membered heterocyclyl are optionally substituted with 1-3 halogen substituents; R5aand R5bare each independently selected from hydrogen and C1-C6-alkyl; or R5aand R5b, taken together with the carbon atom to which they are attached, form a C3- C10-cycloalkyl; R6aand R6bare each independently selected from hydrogen, 5- to 14-membered heteroaryl, and C6-C10-aryl; wherein said 5- to 14-membered heteroaryl, and C6-C10-aryl are optionally substituted with 1-3 substituents independently selected from halogen, C1- C6-alkyl, halo-C1-C6-alkyl, C3-C10-cycloalkyl, and 5- to 14-membered heteroaryl; and R7is selected hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, and 5- to 14-membered heteroaryl. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: (i) X, Y and Z are CH; or (ii) X and Z are CH and Y is N; or (iii) X is N and Y and Z are CH; or (iv) X is CH and Y and Z are N; or (v) X and Y are N and Z is CH; or (vi) X and Z are N and Y is CH. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: (i) X and Y are CH and Z is CRZ; wherein RZis selected from hydrogen and C1-C6-alkyl; or (ii) X and Z are CH and Y is N; or (iii) X is N and Y and Z are CH. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: (i) X, Y and Z are CH; or (ii) X and Z are CH and Y is N; or (iii) X is N and Y and Z are CH. In a preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: (i) X, Y are CH and Z is CRZ; wherein RZis selected from hydrogen and methyl; or (ii) X and Z are CH and Y is N. In a preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: (i) X, Y and Z are CH; or (ii) X and Z are CH and Y is N. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein X, Y and Z are CH. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein X and Z are CH and Y is N. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R1is selected from hydrogen, halogen, cyano, C1-C6-alkyl, C2-C6-alkynyl, halo-C1-C6- alkyl, hydroxy-C1-C6-alkyl, C1-C6-alkoxy, and a group ; A is selected from 3- to 6-membered heterocyclyl comprising 1 to 3 heteroatoms selected from N, O, and S, 5- to 6-membered heteroaryl comprising 1 to 3 heteroatoms selected from N, O, and S, phenyl, and C3-C6-cycloalkyl; L is selected from a covalent bond, –CH2–, and –NRL–; RLis hydrogen; and R1ais selected from hydrogen, halogen, C1-C6-alkyl, and halo-C1-C6-alkyl. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R1is selected from hydrogen, fluoro, chloro, bromo, cyano, methyl, ethyl, prop-1-ynyl, hydroxymethyl, CHF2, methoxy, and a group ; A is selected from azetidine, tetrahydrofurane, tetrahydropyrane, pyrrolidine, pyrazole, phenyl, pyridyl, and cyclopropyl; L is selected from a covalent bond, –CH2–, and –NRL–; RLis hydrogen; and R1ais selected from hydrogen, chloro, methyl, and CF3. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R1is selected from hydrogen, halogen, cyano, C1-C6-alkyl, halo-C1-C6-alkyl, hydroxy- C1-C6-alkyl, C1-C6-alkoxy, and a group A is selected from 3- to 6-membered heterocyclyl comprising 1 to 3 heteroatoms selected from N, O, and S, 5- to 6-membered heteroaryl comprising 1 to 3 heteroatoms selected from N, O, and S, phenyl, and C3-C6-cycloalkyl; L is selected from a covalent bond and –NRL–; RLis hydrogen; and R1ais selected from hydrogen, halogen, and C1-C6-alkyl. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein R1is selected from hydrogen, halogen, cyano, C1-C6-alkyl, and C3-C10-cycloalkyl. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R1is selected from hydrogen, fluoro, chloro, bromo, cyano, methyl, hydroxymethyl, CHF2, methoxy, and a group A is selected from azetidine, pyrrolidine, pyrazole, phenyl, and cyclopropyl; L is selected from a covalent bond and –NRL–; RLis hydrogen; and R1ais selected from hydrogen, chloro, and methyl. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein R1is selected from hydrogen, fluoro, chloro, cyano, methyl, and cyclopropyl. In a preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein R1is selected from hydrogen, halogen, and C1-C6-alkyl. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein R1is selected from hydrogen, fluoro, and methyl. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein R1is hydrogen. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R2ais selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, C1-C6-alkyl-NH-C1-C6- alkyl-, C3-C10-cycloalkyl, phenyl-C1-C6-alkyl, and R2c-O-C1-C6-alkyl; wherein said phenyl is optionally substituted with 1 halogen substituent; R2bis hydrogen; and R2cis selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, and phenyl; wherein said phenyl is optionally substituted with 1 halogen substituent; or R2aand R2b, taken together with the carbon atom to which they are attached, form a C3-C6- cycloalkyl. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R2ais selected from hydrogen, methyl, ethyl, CH2F, CHF2, CF3, CH2CHF2, CH3N-CH2-, hydroxymethyl, methoxymethyl, phenoxymethyl, chlorophenoxymethyl, fluorophenylethyl, CHF2-O-CH2-, CF3-O-CH2-, and cyclopropyl; and R2bis hydrogen; or R2aand R2b, taken together with the carbon atom to which they are attached, form a cyclopropyl or a cyclobutyl. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R2ais selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, C1-C6-alkyl-NH-C1-C6- alkyl-, C3-C10-cycloalkyl, and R2c-O-C1-C6-alkyl; R2bis hydrogen; and R2cis selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, and phenyl; or R2aand R2b, taken together with the carbon atom to which they are attached, form a C3-C6- cycloalkyl. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R2ais selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, C1-C6-alkyl-NH-C1-C6- alkyl-, C1-C6-alkoxy-C1-C6-alkyl, and halo-C1-C6-alkoxy-C1-C6-alkyl; and R2bis hydrogen. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R2ais selected from hydrogen, methyl, ethyl, CH2F, CHF2, CF3, CH3N-CH2-, hydroxymethyl, methoxymethyl, phenoxymethyl, CHF2-O-CH2-, CF3-O-CH2-, and cyclopropyl; and R2bis hydrogen; or R2aand R2b, taken together with the carbon atom to which they are attached, form a cyclopropyl or a cyclobutyl. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R2ais selected from hydrogen, methyl, ethyl, CH2F, CHF2, CF3, CH3N-CH2-, methoxymethyl, CHF2-O-CH2-, and CF3-O-CH2-; and R2bis hydrogen. In a preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R2ais C1-C6-alkyl; and R2bis hydrogen. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R2ais methyl; and R2bis hydrogen. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein R3is selected from C1-C6-alkyl and halo- C1-C6-alkyl. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein R3is selected from methyl and CHF2. In a preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein R3is C1-C6-alkyl. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein R3is methyl. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R4ais selected from hydrogen, halogen, hydroxy, C1-C6-alkyl, 5- to 14-membered heteroaryl, and C6-C10-aroyl; wherein said 5- to 14-membered heteroaryl is optionally substituted with 1 substituent selected from halogen and hydroxy-C1-C6- alkyl; and R4bis selected from hydrogen, halogen, and C1-C6-alkyl; or R4aand R4b, taken together with the carbon atom to which they are attached, form a C3- C10-cycloalkyl; or R4aand R7, taken together with the carbon atoms to which they are attached, form a C3-C6- cycloalkyl; R5aand R5bare each independently selected from hydrogen and C1-C6-alkyl; or R5aand R5b, taken together with the carbon atom to which they are attached, form a C3- C10-cycloalkyl or oxo; R6ais selected from hydrogen, 5- to 14-membered heteroaryl, and C6-C10-aryl; wherein said 5- to 14-membered heteroaryl, and C6-C10-aryl are substituted with 1-3 substituents independently selected from halogen, C1-C6-alkyl, C3-C10-cycloalkyl, and 5- to 14-membered heteroaryl; R6bis hydrogen; and R7is selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, and 5- to 14-membered heteroaryl. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R4ais selected from hydrogen, fluoro, hydroxy, methyl, benzoyl, pyridyl, triazolyl, 1,2,4- triazolyl, and pyrazolyl; wherein said pyridyl, triazolyl, 1,2,4-triazolyl, and pyrazolyl is optionally substituted with 1 substituent selected from chloro, bromo, and hydroxymethyl; and R4bis selected from hydrogen, fluoro, and methyl; or R4aand R4b, taken together with the carbon atom to which they are attached, form a cyclopropyl; or R4aand R7, taken together with the carbon atoms to which they are attached, form a cyclopropyl; R5aand R5bare each independently selected from hydrogen and methyl; or R5aand R5b, taken together with the carbon atom to which they are attached, form a cyclopropyl or oxo; R6ais selected from hydrogen, pyrazolyl, pyridyl, pyridazinyl, isoxazolyl, 1,2,4- oxadiazolyl, and phenyl; wherein said pyrazolyl, pyridyl, pyridazinyl, isoxazolyl, 1,2,4-oxadiazolyl, and phenyl are substituted with 1-3 substituents independently selected from fluoro, chloro, bromo, methyl, cyclopropyl, and pyridyl; R6bis hydrogen; and R7is selected from hydrogen, methyl, CHF2, CF3, and imidazolyl. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R4ais selected from hydrogen, halogen, hydroxy, C1-C6-alkyl, 5- to 14-membered heteroaryl, and C6-C10-aroyl; wherein said 5- to 14-membered heteroaryl is optionally substituted with 1 substituent selected from halogen and hydroxy-C1-C6- alkyl; and R4bis selected from hydrogen, halogen, and C1-C6-alkyl; or R4aand R4b, taken together with the carbon atom to which they are attached, form a C3- C10-cycloalkyl; or R4aand R7, taken together with the carbon atoms to which they are attached, form a C3-C6- cycloalkyl; R5aand R5bare each independently selected from hydrogen and C1-C6-alkyl; or R5aand R5b, taken together with the carbon atom to which they are attached, form a C3- C10-cycloalkyl; R6ais selected from hydrogen, 5- to 14-membered heteroaryl, and C6-C10-aryl; wherein said 5- to 14-membered heteroaryl, and C6-C10-aryl are substituted with 1-3 substituents independently selected from halogen, C1-C6-alkyl, C3-C10-cycloalkyl, and 5- to 14-membered heteroaryl; R6bis hydrogen; and R7is selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, and 5- to 14-membered heteroaryl. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R4ais selected from hydrogen, halogen, hydroxy, C1-C6-alkyl, 5- to 14-membered heteroaryl, and C6-C10-aroyl; wherein said 5- to 14-membered heteroaryl is optionally substituted with 1 substituent selected from halogen and hydroxy-C1-C6- alkyl; and R4bis selected from hydrogen, halogen, and C1-C6-alkyl; or R4aand R4b, taken together with the carbon atom to which they are attached, form a C3- C10-cycloalkyl; R5aand R5bare each independently selected from hydrogen and C1-C6-alkyl; or R5aand R5b, taken together with the carbon atom to which they are attached, form a C3- C10-cycloalkyl; R6ais selected from hydrogen, 5- to 14-membered heteroaryl, and C6-C10-aryl; wherein said 5- to 14-membered heteroaryl, and C6-C10-aryl are substituted with 1-3 substituents independently selected from halogen, C1-C6-alkyl, C3-C10-cycloalkyl, and 5- to 14-membered heteroaryl; R6bis hydrogen; and R7is selected from hydrogen, halo-C1-C6-alkyl, and 5- to 14-membered heteroaryl. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R4ais selected from hydrogen, fluoro, hydroxy, methyl, benzoyl, pyridyl, triazolyl, 1,2,4- triazolyl, and pyrazolyl; wherein said pyridyl, triazolyl, 1,2,4-triazolyl, and pyrazolyl is optionally substituted with 1 substituent selected from chloro, bromo, and hydroxymethyl; and R4bis selected from hydrogen, fluoro, and methyl; or R4aand R4b, taken together with the carbon atom to which they are attached, form a cyclopropyl; or R4aand R7, taken together with the carbon atoms to which they are attached, form a cyclopropyl; R5aand R5bare each independently selected from hydrogen and methyl; or R5aand R5b, taken together with the carbon atom to which they are attached, form a cyclopropyl; R6ais selected from hydrogen, pyrazolyl, pyridyl, pyridazinyl, isoxazolyl, 1,2,4- oxadiazolyl, and phenyl; wherein said pyrazolyl, pyridyl, pyridazinyl, isoxazolyl, 1,2,4-oxadiazolyl, and phenyl are substituted with 1-3 substituents independently selected from fluoro, chloro, bromo, methyl, cyclopropyl, and pyridyl; R6bis hydrogen; and R7is selected from hydrogen, methyl, CHF2, CF3, and imidazolyl. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R4ais selected from hydrogen, fluoro, hydroxy, methyl, benzoyl, pyridyl, triazolyl, 1,2,4- triazolyl, and pyrazolyl; wherein said pyridyl, triazolyl, 1,2,4-triazolyl, and pyrazolyl is optionally substituted with 1 substituent selected from chloro, bromo, and hydroxymethyl; and R4bis selected from hydrogen, fluoro, and methyl; or R4aand R4b, taken together with the carbon atom to which they are attached, form a cyclopropyl; R5aand R5bare each independently selected from hydrogen and methyl; or R5aand R5b, taken together with the carbon atom to which they are attached, form a cyclopropyl; R6ais selected from hydrogen, pyrazolyl, pyridyl, pyridazinyl, isoxazolyl, 1,2,4- oxadiazolyl, and phenyl; wherein said pyrazolyl, pyridyl, pyridazinyl, isoxazolyl, 1,2,4-oxadiazolyl, and phenyl are substituted with 1-3 substituents independently selected from fluoro, chloro, bromo, methyl, cyclopropyl, and pyridyl; R6bis hydrogen; and R7is selected from hydrogen, CF3, and imidazolyl. In a preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R4ais selected from hydrogen, halogen, and C1-C6-alkyl; R4bis selected from hydrogen and halogen; R5ais hydrogen; R5bis hydrogen; R6ais selected from hydrogen and 5- to 14-membered heteroaryl; wherein said 5- to 14- membered heteroaryl is substituted with 1 substituent selected from halogen, C1-C6- alkyl, C3-C10-cycloalkyl, and 5- to 14-membered heteroaryl; R6bis hydrogen; and R7is selected from hydrogen, halo-C1-C6-alkyl, and 5- to 14-membered heteroaryl. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R4ais selected from hydrogen, fluoro, and methyl; R4bis selected from hydrogen and fluoro; R5ais hydrogen; R5bis hydrogen; R6ais selected from hydrogen, pyridyl, and pyrazolyl; wherein said pyridyl and pyrazolyl are substituted with 1 substituent selected from bromo, methyl, cyclopropyl, and pyridyl; R6bis hydrogen; and R7is selected from hydrogen, CF3, and imidazolyl. In a preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R4ais selected from hydrogen and halogen; R4bis selected from hydrogen and halogen; R5ais hydrogen; R5bis hydrogen; R6ais selected from hydrogen and 5- to 6-membered heteroaryl; wherein said 5- to 6- membered heteroaryl is substituted with 1 halogen substituent; R6bis hydrogen; and R7is hydrogen. In a preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein R4aand R4bare each independently selected from hydrogen and halogen. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein R5aand R5bare both hydrogen. In a preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R6ais selected from hydrogen and 5- to 6-membered heteroaryl; wherein said 5- to 6- membered heteroaryl is substituted with 1 halogen substituent; and R6bis hydrogen. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein R7is hydrogen. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R4ais selected from hydrogen and fluoro; R4bis selected from hydrogen and fluoro; R5ais hydrogen; R5bis hydrogen; R6ais selected from hydrogen and bromopyridyl; R6bis hydrogen; and R7is hydrogen. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein R4aand R4bare each independently selected from hydrogen and fluoro. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: R6ais selected from hydrogen and bromopyridyl; and R6bis hydrogen. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein the group In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: U is selected from O, S, and NRU; V is a covalent bond or CHRV; RUis cyano; and RVis halo-C1-C6-alkyl. In a preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: U is selected from O, S, and NRU; V is a covalent bond or CHRV; RUis cyano; and RVis CF3. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein U is O and V is a covalent bond, represented by Formula (Ia): wherein X, Y, Z, and R1to R7are as defined herein. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: (i) X and Y are CH and Z is CRZ; or (ii) X and Z are CH and Y is N; or (iii) X is N and Y and Z are CH; U is selected from O, S, and NRU; V is a covalent bond or CHRV; A is selected from 3- to 6-membered heterocyclyl comprising 1 to 3 heteroatoms selected from N, O, and S, 5- to 6-membered heteroaryl comprising 1 to 3 heteroatoms selected from N, O, and S, phenyl, and C3-C6-cycloalkyl; L is selected from a covalent bond, –CH2–, and –NRL–; RLis hydrogen; RUis cyano; RVis halo-C1-C6-alkyl; RZis selected from hydrogen and C1-C6-alkyl; R1is selected from hydrogen, halogen, cyano, C1-C6-alkyl, C2-C6-alkynyl, halo-C1-C6- alkyl, hydroxy-C1-C6-alkyl, C1-C6-alkoxy, and a group ; R1ais selected from hydrogen, halogen, C1-C6-alkyl, and halo-C1-C6-alkyl; R2ais selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, C1-C6-alkyl-NH-C1-C6- alkyl-, C3-C10-cycloalkyl, phenyl-C1-C6-alkyl, and R2c-O-C1-C6-alkyl; wherein said phenyl is optionally substituted with 1 halogen substituent; R2bis hydrogen; and R2cis selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, and phenyl; wherein said phenyl is optionally substituted with 1 halogen substituent; or R2aand R2b, taken together with the carbon atom to which they are attached, form a C3-C6- cycloalkyl; R3is selected from C1-C6-alkyl and halo-C1-C6-alkyl; R4ais selected from hydrogen, halogen, hydroxy, C1-C6-alkyl, 5- to 14-membered heteroaryl, and C6-C10-aroyl; wherein said 5- to 14-membered heteroaryl is optionally substituted with 1 substituent selected from halogen and hydroxy-C1-C6- alkyl; and R4bis selected from hydrogen, halogen, and C1-C6-alkyl; or R4aand R4b, taken together with the carbon atom to which they are attached, form a C3- C10-cycloalkyl; or R4aand R7, taken together with the carbon atoms to which they are attached, form a C3-C6- cycloalkyl; R5aand R5bare each independently selected from hydrogen and C1-C6-alkyl; or R5aand R5b, taken together with the carbon atom to which they are attached, form a C3- C10-cycloalkyl or oxo; R6ais selected from hydrogen, 5- to 14-membered heteroaryl, and C6-C10-aryl; wherein said 5- to 14-membered heteroaryl, and C6-C10-aryl are substituted with 1-3 substituents independently selected from halogen, C1-C6-alkyl, C3-C10-cycloalkyl, and 5- to 14-membered heteroaryl; R6bis hydrogen; and R7is selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, and 5- to 14-membered heteroaryl. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: (i) X and Y are CH and Z is CRZ; or (ii) X and Z are CH and Y is N; or (iii) X is N and Y and Z are CH; U is selected from O, S, and NRU; V is a covalent bond or CHRV; A is selected from azetidine, tetrahydrofurane, tetrahydropyrane, pyrrolidine, pyrazole, phenyl, pyridyl, and cyclopropyl; L is selected from a covalent bond, –CH2–, and –NRL–; RLis hydrogen; RUis cyano; RVis CF3; RZis selected from hydrogen and methyl; R1is selected from hydrogen, fluoro, chloro, bromo, cyano, methyl, ethyl, prop-1-ynyl, hydroxymethyl, CHF2, methoxy, and a group ;; R1ais selected from hydrogen, chloro, methyl, and and CF3; R2ais selected from hydrogen, methyl, ethyl, CH2F, CHF2, CF3, CH2CHF2, CH3N-CH2-, hydroxymethyl, methoxymethyl, phenoxymethyl, chlorophenoxymethyl, fluorophenylethyl, CHF2-O-CH2-, CF3-O-CH2-, and cyclopropyl; and R2bis hydrogen; or R2aand R2b, taken together with the carbon atom to which they are attached, form a cyclopropyl or a cyclobutyl; R3is selected from methyl and CHF2; R4ais selected from hydrogen, fluoro, hydroxy, methyl, benzoyl, pyridyl, triazolyl, 1,2,4- triazolyl, and pyrazolyl; wherein said pyridyl, triazolyl, 1,2,4-triazolyl, and pyrazolyl is optionally substituted with 1 substituent selected from chloro, bromo, and hydroxymethyl; and R4bis selected from hydrogen, fluoro, and methyl; or R4aand R4b, taken together with the carbon atom to which they are attached, form a cyclopropyl; or R4aand R7, taken together with the carbon atoms to which they are attached, form a cyclopropyl; R5aand R5bare each independently selected from hydrogen and methyl; or R5aand R5b, taken together with the carbon atom to which they are attached, form a cyclopropyl or oxo; R6ais selected from hydrogen, pyrazolyl, pyridyl, pyridazinyl, isoxazolyl, 1,2,4- oxadiazolyl, and phenyl; wherein said pyrazolyl, pyridyl, pyridazinyl, isoxazolyl, 1,2,4-oxadiazolyl, and phenyl are substituted with 1-3 substituents independently selected from fluoro, chloro, bromo, methyl, cyclopropyl, and pyridyl; R6bis hydrogen; and R7is selected from hydrogen, methyl, CHF2, CF3, and imidazolyl. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: (i) X, Y and Z are CH; or (ii) X and Z are CH and Y is N; or (iii) X is N and Y and Z are CH; U is selected from O, S, and NRU; V is a covalent bond or CHRV; A is selected from 3- to 6-membered heterocyclyl comprising 1 to 3 heteroatoms selected from N, O, and S, 5- to 6-membered heteroaryl comprising 1 to 3 heteroatoms selected from N, O, and S, phenyl, and C3-C6-cycloalkyl; L is selected from a covalent bond and –NRL–; RLis hydrogen; RUis cyano; RVis halo-C1-C6-alkyl; R1is selected from hydrogen, halogen, cyano, C1-C6-alkyl, halo-C1-C6-alkyl, hydroxy- C1-C6-alkyl, C1-C6-alkoxy, and a group R1ais selected from hydrogen, halogen, and C1-C6-alkyl; R2ais selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, C1-C6-alkyl-NH-C1-C6- alkyl-, C3-C10-cycloalkyl, and R2c-O-C1-C6-alkyl; R2bis hydrogen; and R2cis selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, and phenyl; or R2aand R2b, taken together with the carbon atom to which they are attached, form a C3-C6- cycloalkyl; R3is C1-C6-alkyl; R4ais selected from hydrogen, halogen, hydroxy, C1-C6-alkyl, 5- to 14-membered heteroaryl, and C6-C10-aroyl; wherein said 5- to 14-membered heteroaryl is optionally substituted with 1 substituent selected from halogen and hydroxy-C1-C6- alkyl; and R4bis selected from hydrogen, halogen, and C1-C6-alkyl; or R4aand R4b, taken together with the carbon atom to which they are attached, form a C3- C10-cycloalkyl; or R4aand R7, taken together with the carbon atoms to which they are attached, form a C3-C6- cycloalkyl; R5aand R5bare each independently selected from hydrogen and C1-C6-alkyl; or R5aand R5b, taken together with the carbon atom to which they are attached, form a C3- C10-cycloalkyl; R6ais selected from hydrogen, 5- to 14-membered heteroaryl, and C6-C10-aryl; wherein said 5- to 14-membered heteroaryl, and C6-C10-aryl are substituted with 1-3 substituents independently selected from halogen, C1-C6-alkyl, C3-C10-cycloalkyl, and 5- to 14-membered heteroaryl; R6bis hydrogen; and R7is selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, and 5- to 14-membered heteroaryl. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: (i) X, Y and Z are CH; or (ii) X and Z are CH and Y is N; or (iii) X is N and Y and Z are CH; U is selected from O, S, and NRU; V is a covalent bond or CHRV; A is selected from azetidine, pyrrolidine, pyrazole, phenyl, and cyclopropyl; L is selected from a covalent bond and –NRL–; RLis hydrogen; RUis cyano; RVis CF3; R1is selected from hydrogen, fluoro, chloro, bromo, cyano, methyl, hydroxymethyl, CHF2, methoxy, and a group R1ais selected from hydrogen, chloro, and methyl; R2ais selected from hydrogen, methyl, ethyl, CH2F, CHF2, CF3, CH3N-CH2-, hydroxymethyl, methoxymethyl, phenoxymethyl, CHF2-O-CH2-, CF3-O-CH2-, and cyclopropyl; and R2bis hydrogen; or R2aand R2b, taken together with the carbon atom to which they are attached, form a cyclopropyl or a cyclobutyl; R3is methyl; R4ais selected from hydrogen, fluoro, hydroxy, methyl, benzoyl, pyridyl, triazolyl, 1,2,4- triazolyl, and pyrazolyl; wherein said pyridyl, triazolyl, 1,2,4-triazolyl, and pyrazolyl is optionally substituted with 1 substituent selected from chloro, bromo, and hydroxymethyl; and R4bis selected from hydrogen, fluoro, and methyl; or R4aand R4b, taken together with the carbon atom to which they are attached, form a cyclopropyl; or R4aand R7, taken together with the carbon atoms to which they are attached, form a cyclopropyl; R5aand R5bare each independently selected from hydrogen and methyl; or R5aand R5b, taken together with the carbon atom to which they are attached, form a cyclopropyl; R6ais selected from hydrogen, pyrazolyl, pyridyl, pyridazinyl, isoxazolyl, 1,2,4- oxadiazolyl, and phenyl; wherein said pyrazolyl, pyridyl, pyridazinyl, isoxazolyl, 1,2,4-oxadiazolyl, and phenyl are substituted with 1-3 substituents independently selected from fluoro, chloro, bromo, methyl, cyclopropyl, and pyridyl; R6bis hydrogen; and R7is selected from hydrogen, methyl, CHF2, CF3, and imidazolyl. In a preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: (i) X, Y and Z are CH; or (ii) X and Z are CH and Y is N; U is O; V is a covalent bond; R1is selected from hydrogen, halogen, and C1-C6-alkyl; R2ais C1-C6-alkyl; and R2bis hydrogen; R3is C1-C6-alkyl; R4ais selected from hydrogen, halogen, and C1-C6-alkyl; R4bis selected from hydrogen and halogen; R5ais hydrogen; R5bis hydrogen; R6ais selected from hydrogen and 5- to 14-membered heteroaryl; wherein said 5- to 14- membered heteroaryl is substituted with 1 substituent selected from halogen, C1-C6- alkyl, C3-C10-cycloalkyl, and 5- to 14-membered heteroaryl; R6bis hydrogen; and R7is selected from hydrogen, halo-C1-C6-alkyl, and 5- to 14-membered heteroaryl. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: (i) X, Y and Z are CH; or (ii) X and Z are CH and Y is N; U is O; V is a covalent bond; R1is selected from hydrogen, fluoro, and methyl; R2ais methyl; and R2bis hydrogen; R3is methyl; R4ais selected from hydrogen, fluoro, and methyl; R4bis selected from hydrogen and fluoro; R5ais hydrogen; R5bis hydrogen; R6ais selected from hydrogen, pyridyl, and pyrazolyl; wherein said pyridyl and pyrazolyl are substituted with 1 substituent selected from bromo, methyl, cyclopropyl, and pyridyl; R6bis hydrogen; and R7is selected from hydrogen, CF3, and imidazolyl. In one preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: (i) X, Y and Z are CH; or (ii) X and Z are CH and Y is N; or (iii) X is N and Y and Z are CH; U is selected from O, S, and NRU; V is a covalent bond or CHRV; RUis cyano; and RVis halo-C1-C6-alkyl. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: (i) X, Y and Z are CH; or (ii) X and Z are CH and Y is N; or (iii) X is N and Y and Z are CH; U is selected from O, S, and NRU; V is a covalent bond or CHRV; RUis cyano; and RVis CF3. In a preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: (i) X, Y and Z are CH; or (ii) X and Z are CH and Y is N; U is O; and V is a covalent bond. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: X is CH or N; R1is selected from hydrogen, halogen, cyano, C1-C6-alkyl, and C3-C10-cycloalkyl; R2ais selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, C1-C6-alkyl-NH-C1-C6- alkyl-, C1-C6-alkoxy-C1-C6-alkyl, and halo-C1-C6-alkoxy-C1-C6-alkyl; R2bis hydrogen; R3is C1-C6-alkyl; R4ais selected from hydrogen, halogen, hydroxy, C1-C6-alkyl, 5- to 14-membered heteroaryl, and C6-C10-aroyl; wherein said 5- to 14-membered heteroaryl is optionally substituted with 1 substituent selected from halogen and hydroxy-C1-C6- alkyl; and R4bis selected from hydrogen, halogen, and C1-C6-alkyl; or R4aand R4b, taken together with the carbon atom to which they are attached, form a C3- C10-cycloalkyl; R5aand R5bare each independently selected from hydrogen and C1-C6-alkyl; or R5aand R5b, taken together with the carbon atom to which they are attached, form a C3- C10-cycloalkyl; R6ais selected from hydrogen, 5- to 14-membered heteroaryl, and C6-C10-aryl; wherein said 5- to 14-membered heteroaryl, and C6-C10-aryl are substituted with 1-3 substituents independently selected from halogen, C1-C6-alkyl, C3-C10-cycloalkyl, and 5- to 14-membered heteroaryl; R6bis hydrogen; and R7is selected from hydrogen, halo-C1-C6-alkyl, and 5- to 14-membered heteroaryl. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: X is CH or N; R1is selected from hydrogen, fluoro, chloro, cyano, methyl, and cyclopropyl; R2ais selected from hydrogen, methyl, ethyl, CH2F, CHF2, CF3, CH3N-CH2-, methoxymethyl, CHF2-O-CH2-, and CF3-O-CH2-; R2bis hydrogen; R3is methyl; R4ais selected from hydrogen, fluoro, hydroxy, methyl, benzoyl, pyridyl, triazolyl, 1,2,4- triazolyl, and pyrazolyl; wherein said pyridyl, triazolyl, 1,2,4-triazolyl, and pyrazolyl is optionally substituted with 1 substituent selected from chloro, bromo, and hydroxymethyl; and R4bis selected from hydrogen, fluoro, and methyl; or R4aand R4b, taken together with the carbon atom to which they are attached, form a cyclopropyl; R5aand R5bare each independently selected from hydrogen and methyl; or R5aand R5b, taken together with the carbon atom to which they are attached, form a cyclopropyl; R6ais selected from hydrogen, pyrazolyl, pyridyl, pyridazinyl, isoxazolyl, 1,2,4- oxadiazolyl, and phenyl; wherein said pyrazolyl, pyridyl, pyridazinyl, isoxazolyl, 1,2,4-oxadiazolyl, and phenyl are substituted with 1-3 substituents independently selected from fluoro, chloro, bromo, methyl, cyclopropyl, and pyridyl; R6bis hydrogen; and R7is selected from hydrogen, CF3, and imidazolyl. In a preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: X is CH; R1is hydrogen; R2ais C1-C6-alkyl; and R2bis hydrogen; R3is C1-C6-alkyl; R4ais selected from hydrogen, halogen, and C1-C6-alkyl; R4bis selected from hydrogen and halogen; R5ais hydrogen; R5bis hydrogen; R6ais selected from hydrogen and 5- to 14-membered heteroaryl; wherein said 5- to 14- membered heteroaryl is substituted with 1 substituent selected from halogen, C1-C6- alkyl, C3-C10-cycloalkyl, and 5- to 14-membered heteroaryl; R6bis hydrogen; and R7is selected from hydrogen, halo-C1-C6-alkyl, and 5- to 14-membered heteroaryl. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein: X is CH; R1is hydrogen; R2ais methyl; and R2bis hydrogen; R3is methyl; R4ais selected from hydrogen, fluoro, and methyl; R4bis selected from hydrogen and fluoro; R5ais hydrogen; R5bis hydrogen; R6ais selected from hydrogen, pyridyl, and pyrazolyl; wherein said pyridyl and pyrazolyl are substituted with 1 substituent selected from bromo, methyl, cyclopropyl, and pyridyl; R6bis hydrogen; and R7is selected from hydrogen, CF3, and imidazolyl. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is selected from: 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-(2,2,2-trifluoro-1-tetrahydrofuran-3-yl-ethyl)urea; 1-[(3-chloro-4-pyridyl)methyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-[(3-fluoro-4-pyridyl)methyl]-1-methyl-urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-(4-pyridylmethyl)urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)propyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-(4-pyridyl)propyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)propyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-(4-pyridyl)propyl]urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[(3-methyl-4-pyridyl)methyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyridazin-4-ylethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyridazin-4-ylethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyridazin-4-ylethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyridazin-4-ylethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyridazin-4-ylethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyridazin-4-ylethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyridazin-4-ylethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyridazin-4-ylethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyridazin-4-ylethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyridazin-4-ylethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyridazin-4-ylethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyridazin-4-ylethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-(4-pyridylmethyl)urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-(4-pyridylmethyl)urea; 3-(4-benzoyltetrahydrofuran-3-yl)-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea; 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(3R)-3-(trifluoromethyl)tetrahydrofuran-3-yl]urea; 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(3S)-3-(trifluoromethyl)tetrahydrofuran-3-yl]urea; 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(3R)-3-(trifluoromethyl)tetrahydrofuran-3-yl]urea; 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(3S)-3-(trifluoromethyl)tetrahydrofuran-3-yl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(3-methyl-4-pyridyl)methyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(3-methyl-4-pyridyl)methyl]urea; 1-[(3-bromo-4-pyridyl)methyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyrimidin-4-ylethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyrimidin-4-ylethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyrimidin-4-ylethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyrimidin-4-ylethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-fluoro-4-pyridyl)ethyl]-1-methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-fluoro-4-pyridyl)ethyl]-1-methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-fluoro-4-pyridyl)ethyl]-1-methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-fluoro-4-pyridyl)ethyl]-1-methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-fluoro-4-pyridyl)ethyl]-1-methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-fluoro-4-pyridyl)ethyl]-1-methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-fluoro-4-pyridyl)ethyl]-1-methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-fluoro-4-pyridyl)ethyl]-1-methyl-urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-[[3-(hydroxymethyl)-4-pyridyl]methyl]-1-methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(3-methyl-4-pyridyl)ethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-(3-methyl-4-pyridyl)ethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(3-methyl-4-pyridyl)ethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-(3-methyl-4-pyridyl)ethyl]urea; 1-[(3-cyclopropyl-4-pyridyl)methyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea; 1-[(3-bromo-4-pyridyl)methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-urea; 1-[(3-bromo-4-pyridyl)methyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-urea; 1-[[3-(azetidin-1-yl)-4-pyridyl]methyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[2-phenoxy-1-(4-pyridyl)ethyl]urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-[2-methoxy-1-(4-pyridyl)ethyl]-1-methyl-urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-[(3-methoxy-4-pyridyl)methyl]-1-methyl-urea; 1-[1-(3-chloro-4-pyridyl)ethyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[(3-pyrrolidin-1-yl-4-pyridyl)methyl]urea; 1-[(S)-cyclopropyl(4-pyridyl)methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-urea; 1-[(S)-cyclopropyl(4-pyridyl)methyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-urea; 1-[(R)-cyclopropyl(4-pyridyl)methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-urea; 1-[(R)-cyclopropyl(4-pyridyl)methyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[1-(4-pyridyl)cyclopropyl]urea; 3-[(2R,3S)-2-(5-bromo-2-methyl-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea; 3-[(2S,3R)-2-(5-bromo-2-methyl-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea; 1-[(1S)-1-(3-chloro-4-pyridyl)ethyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-urea; 1-[(1S)-1-(3-chloro-4-pyridyl)ethyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-urea; 1-[(1R)-1-(3-chloro-4-pyridyl)ethyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-urea; 1-[(1R)-1-(3-chloro-4-pyridyl)ethyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[1-(4-pyridyl)cyclopropyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[1-(4-pyridyl)cyclopropyl]urea; 1-[[3-(3-chloroanilino)-4-pyridyl]methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl- urea; 1-[[3-(3-chloroanilino)-4-pyridyl]methyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl- urea; 3-[(3S)-4,4-difluoro-3-methyl-tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea; 3-[(3R)-4,4-difluoro-3-methyl-tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-2-phenoxy-1-(4-pyridyl)ethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-2-phenoxy-1-(4-pyridyl)ethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-2-phenoxy-1-(4-pyridyl)ethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-2-phenoxy-1-(4-pyridyl)ethyl]urea; 1-methyl-3-[(1R,5R)-3-oxabicyclo[3.1.0]hexan-1-yl]-1-[(1S)-1-(4-pyridyl)ethyl]urea; 1-methyl-3-[(1S,5S)-3-oxabicyclo[3.1.0]hexan-1-yl]-1-[(1S)-1-(4-pyridyl)ethyl]urea; 1-methyl-3-[(1R,5R)-3-oxabicyclo[3.1.0]hexan-1-yl]-1-[(1S)-1-(4-pyridyl)ethyl]urea; 1-methyl-3-[(1S,5S)-3-oxabicyclo[3.1.0]hexan-1-yl]-1-[(1S)-1-(4-pyridyl)ethyl]urea; 1-[[3-(difluoromethyl)-4-pyridyl]methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl- urea; 1-[[3-(difluoromethyl)-4-pyridyl]methyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl- urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[1-(4-pyridyl)cyclobutyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[1-(4-pyridyl)cyclobutyl]urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[[3-(1H-pyrazol-5-yl)-4-pyridyl]methyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-2-hydroxy-1-(4-pyridyl)ethyl]-1-methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-2-hydroxy-1-(4-pyridyl)ethyl]-1-methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-2-hydroxy-1-(4-pyridyl)ethyl]-1-methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-2-hydroxy-1-(4-pyridyl)ethyl]-1-methyl-urea; 3-[3-(difluoromethyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(3-phenyl-4-pyridyl)methyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(3-phenyl-4-pyridyl)methyl]urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]thiourea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[[3-(3-methyl-1H-pyrazol-5-yl)-4- pyridyl]methyl]urea; 2-cyano-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]guanidine; 1-methyl-3-(5-oxotetrahydrofuran-3-yl)-1-[(1S)-1-(4-pyridyl)ethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-[[(3S)-tetrahydrofuran-3-yl]methyl]-4- pyridyl]methyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-[[(3R)-tetrahydrofuran-3-yl]methyl]-4- pyridyl]methyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-[[(3S)-tetrahydrofuran-3-yl]methyl]-4- pyridyl]methyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-[[(3R)-tetrahydrofuran-3-yl]methyl]-4- pyridyl]methyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-(4-pyridyl)-4-pyridyl]methyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-(3-pyridyl)-4-pyridyl]methyl]urea; 1-[[3-(4-chlorophenyl)-4-pyridyl]methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl- urea; 1-[[3-(2-chlorophenyl)-4-pyridyl]methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl- urea; 1-[[3-(3-chlorophenyl)-4-pyridyl]methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl- urea; 1-[2-(3-chlorophenoxy)-1-(4-pyridyl)ethyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[(3-prop-1-ynyl-4-pyridyl)methyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-(2-pyridyl)-4-pyridyl]methyl]urea; 1-[2-(4-chlorophenoxy)-1-(4-pyridyl)ethyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea; 3-[(3S,4R)-4-hydroxytetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea; 3-[(3R,4S)-4-hydroxytetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-(tetrahydropyran-4-ylmethyl)-4- pyridyl]methyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-(tetrahydropyran-4-ylmethyl)-4- pyridyl]methyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-[4-(trifluoromethyl)phenyl]-4- pyridyl]methyl]urea; [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1-methyl- urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1-methyl- urea]; [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1-methyl- urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1-methyl- urea]; [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1-methyl- urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1-methyl- urea]; [3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1-methyl- urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1-methyl- urea]; [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1-methyl- urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3 yl]-1-[(1R)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1-methyl- urea]; [3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1-methyl- urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1-methyl- urea]; 1-[(1S)-1-(3-bromo-4-pyridyl)ethyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-urea; 1-[(1S)-1-(3-bromo-4-pyridyl)ethyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-urea; 1-[(1R)-1-(3-bromo-4-pyridyl)ethyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-urea; 1-[(1R)-1-(3-bromo-4-pyridyl)ethyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-urea; 1-[(1R)-2-(4-chlorophenoxy)-1-(4-pyridyl)ethyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea; 1-[(1R)-2-(4-chlorophenoxy)-1-(4-pyridyl)ethyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea; 1-[(1S)-2-(4-chlorophenoxy)-1-(4-pyridyl)ethyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea; 1-[(1S)-2-(4-chlorophenoxy)-1-(4-pyridyl)ethyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-3-(4-fluorophenyl)-1-(4-pyridyl)propyl]-1- methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-3-(4-fluorophenyl)-1-(4-pyridyl)propyl]-1- methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-3-(4-fluorophenyl)-1-(4-pyridyl)propyl]-1- methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-3-(4-fluorophenyl)-1-(4-pyridyl)propyl]-1- methyl-urea; 1-[(1S)-3,3-difluoro-1-(4-pyridyl)propyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl- urea; 1-[(1S)-3,3-difluoro-1-(4-pyridyl)propyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl- urea; 1-[(1R)-3,3-difluoro-1-(4-pyridyl)propyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl- urea; 1-[(1R)-3,3-difluoro-1-(4-pyridyl)propyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl- urea; 1-(difluoromethyl)-3-(4,4-difluorotetrahydrofuran-3-yl)-1-(4-pyridylmethyl)urea; [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-ethyl-4-pyridyl)ethyl]-1-methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-ethyl-4-pyridyl)ethyl]-1-methyl-urea]; [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-ethyl-4-pyridyl)ethyl]-1-methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-ethyl-4-pyridyl)ethyl]-1-methyl-urea]; [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-ethyl-4-pyridyl)ethyl]-1-methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-ethyl-4-pyridyl)ethyl]-1-methyl-urea]; [3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-ethyl-4-pyridyl)ethyl]-1-methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-ethyl-4-pyridyl)ethyl]-1-methyl-urea]; [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-ethyl-4-pyridyl)ethyl]-1-methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-ethyl-4-pyridyl)ethyl]-1-methyl-urea]; [3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-ethyl-4-pyridyl)ethyl]-1-methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-ethyl-4-pyridyl)ethyl]-1-methyl-urea]; and 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[2,2,2-trifluoro-1-(4-pyridyl)ethyl]urea]. In one embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is selected from: 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(3RS)-tetrahydrofuran-3-yl]urea; 1-methyl-3-[(3RS, 4RS)-4-methyltetrahydrofuran-3-yl]-1-[(1S)-1-(4-pyridyl)ethyl]urea; 1-methyl-3-[(3RS, 4SR)-4-methyltetrahydrofuran-3-yl]-1-[(1S)-1-(4-pyridyl)ethyl]urea; 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(3RS)-3-(trifluoromethyl)tetrahydrofuran-3- yl]urea; 3-[(3RS)-3-(1H-imidazol-2-yl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea; 1-methyl-3-[(3RS)-3-(1-methylpyrazol-4-yl)tetrahydrofuran-3-yl]-1-[(1S)-1-(4- pyridyl)ethyl]urea; 3-[(2RS,3SR)-2-(5-bromo-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea; 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(2RS,3SR)-2-[5-(3-pyridyl)-3- pyridyl]tetrahydrofuran-3-yl]urea; 3-[(2RS,3SR)-2-(5-cyclopropyl-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea; 3-[(2S,3R)-2-(5-bromo-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea; 3-[(2R,3S)-2-(5-bromo-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea; 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(2R,3S)-2-[5-(3-pyridyl)-3- pyridyl]tetrahydrofuran-3-yl]urea; 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(2S,3R)-2-[5-(3-pyridyl)-3- pyridyl]tetrahydrofuran-3-yl]urea; 3-[(2R,3S)-2-(5-cyclopropyl-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea; and 3-[(2S,3R)-2-(5-cyclopropyl-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea. In a preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is selected from: 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[(3-methyl-4-pyridyl)methyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyridazin-4-ylethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyridazin-4-ylethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyridazin-4-ylethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyridazin-4-ylethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-(4-pyridylmethyl)urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-(4-pyridylmethyl)urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(3-methyl-4-pyridyl)methyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(3-methyl-4-pyridyl)methyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-fluoro-4-pyridyl)ethyl]-1-methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-fluoro-4-pyridyl)ethyl]-1-methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-fluoro-4-pyridyl)ethyl]-1-methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-fluoro-4-pyridyl)ethyl]-1-methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea; and 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[(3-methyl-4-pyridyl)methyl]urea. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyridazin-4- ylethyl]urea. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyridazin-4- ylethyl]urea. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyridazin-4- ylethyl]urea. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyridazin-4- ylethyl]urea. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-(4-pyridylmethyl)urea. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-(4-pyridylmethyl)urea. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(3-methyl-4- pyridyl)methyl]urea. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(3-methyl-4- pyridyl)methyl]urea. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-fluoro-4-pyridyl)ethyl]-1- methyl-urea. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-fluoro-4-pyridyl)ethyl]-1- methyl-urea. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-fluoro-4-pyridyl)ethyl]-1- methyl-urea. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-fluoro-4-pyridyl)ethyl]-1- methyl-urea. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea. In a particularly preferred embodiment, the present invention provides a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea. In a particular embodiment, the present invention provides pharmaceutically acceptable salts of the compounds according to formula (I) as described herein. In a further particular embodiment, the present invention provides compounds according to formula (I) as described herein as free bases. In some embodiments, the compounds of formula (I) are isotopically-labeled by having one or more atoms therein replaced by an atom having a different atomic mass or mass number. Such isotopically-labeled (i.e., radiolabeled) compounds of formula (I) are considered to be within the scope of this disclosure. Examples of isotopes that can be incorporated into the compounds of formula (I) include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, sulfur, fluorine, chlorine, and iodine, such as, but not limited to,2H,3H,11C,13C,14C,13N,15N,15O,17O,18O,31P,32P,35S,18F,36Cl,123I, and125I, respectively. Certain isotopically-labeled compounds of formula (I), for example, those incorporating a radioactive isotope, are useful in drug and / or substrate tissue distribution studies. The radioactive isotopes tritium, i.e.3H, and carbon-14, i.e.,14C, are particularly useful for this purpose in view of their ease of incorporation and ready means of detection. For example, a compound of formula (I) can be enriched with 1, 2, 5, 10, 25, 50, 75, 90, 95, or 99 percent of a given isotope. Substitution with heavier isotopes such as deuterium, i.e.2H, may afford certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements. Thus, in one embodiment, the present invention provides compounds of formula (I) as described herein, wherein one or more hydrogen atoms are replaced by deuterium, preferably wherein 1-4 hydrogen atoms are replaced by deuterium, more prefereably wherein 1-3 hydrogen atoms are replaced by deuterium. Substitution with positron emitting isotopes, such as11C,18F,15O and13N, can be useful in Positron Emission Topography (PET) studies for examining substrate receptor occupancy. Isotopically-labeled compounds of formula (I) can generally be prepared by conventional techniques known to those skilled in the art or by processes analogous to those described in the Examples as set out below using an appropriate isotopically-labeled reagent in place of the non- labeled reagent previously employed. Processes of Manufacturing The preparation of compounds of formula (I) of the present invention may be carried out in sequential or convergent synthetic routes. Syntheses of the invention are shown in the following general schemes. The skills required for carrying out the reaction and purification of the resulting products are known to those persons skilled in the art. The substituents and indices used in the following description of the processes have the significance given herein, unless indicated to the contrary. If one of the starting materials, intermediates or compounds of formula (I) contain one or more functional groups which are not stable or are reactive under the reaction conditions of one or more reaction steps, appropriate protective groups (as described e.g., in “Protective Groups in Organic Chemistry” by T. W. Greene and P. G. M. Wutts, 5th Ed., 2014, John Wiley & Sons, N.Y.) can be introduced before the critical step applying methods well known in the art. Such protective groups can be removed at a later stage of the synthesis using standard methods described in the literature. If starting materials or intermediates contain stereogenic centers, compounds of formula (I) can be obtained as mixtures 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 e.g., be separated into their antipodes via diastereomeric salts by crystallization with optically pure acids or by separation of the antipodes by specific chromatographic methods using either a chiral adsorbent or a chiral eluent. It is equally possible to separate starting materials and intermediates containing stereogenic centers to afford diastereomerically / enantiomerically enriched starting materials and intermediates. Using such diastereomerically / enantiomerically enriched starting materials and intermediates in the synthesis of compounds of formula (I) will typically lead to the respective diastereomerically / enantiomerically enriched compounds of formula (I). A person skilled in the art will acknowledge that in the synthesis of compounds of formula (I) - insofar not desired otherwise - an “orthogonal protection group strategy” will be applied, allowing the cleavage of several protective groups one at a time each without affecting other protective groups in the molecule. The principle of orthogonal protection is well known in the art and has also been described in literature (e.g. Barany and R. B. Merrifield, J. Am. Chem. Soc. 1977, 99, 7363; H. Waldmann et al., Angew. Chem. Int. Ed. Engl.1996, 35, 2056). A person skilled in the art will acknowledge that the sequence of reactions may be varied depending on reactivity and nature of the intermediates. In more detail, the compounds of formula (I) can be manufactured by the methods given below, by the methods given in the examples or by analogous methods. Appropriate reaction conditions for the individual reaction steps are known to a person skilled in the art. Also, for reaction conditions described in literature affecting the described reactions see for example: Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 2nd Edition, Richard C. Larock. John Wiley & Sons, New York, NY.1999). It was found convenient to carry out the reactions in the presence or absence of a solvent. There is no particular restriction on the nature of the solvent to be employed, provided that it has no adverse effect on the reaction or the reagents involved and that it can dissolve the reagents, at least to some extent. The described reactions can take place over a wide range of temperatures, and the precise reaction temperature is not critical to the invention. It is convenient to carry out the described reactions in a temperature range between -78 °C to reflux. The time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents. However, a period of from 0.5 hours to several days will usually suffice to yield the described intermediates and compounds. The reaction sequence is not limited to the one displayed in the schemes, however, depending on the starting materials and their respective reactivity, the sequence of reaction steps can be freely altered. If starting materials or intermediates are not commercially available or their synthesis not described in literature, they can be prepared in analogy to existing procedures for close analogues or as outlined in the experimental section. The following abbreviations are used in the present text: °C = degree Celsius; Boc2O = di-tert-butyl dicarbonate; CataCXium Pd G4 = [di(adamantan-1- yl)(butyl)phosphine](methanesulfonato-κO)[2′-(methylamino)-2-biphenylyl]palladium; CDT = 1,1′-Carbonyl-di-(1,2,4-triazole); CH3CN = acetonitrile; CHCl3= chloroform; Cs2CO3= cesium carbonate; CuI = copper iodide; DCE = dichloroethane; DCM = dichloromethane; DIPEA = N,N- Diisopropylethylamine; DMF = N,N-dimethylformamide; ESI = electrospray ionization; Et2O = diethylether; EtOAc = ethyl acetate; EtOH = ethanol; FC = flash chromatography; h = hour(s); H2= hydrogen; H2O = water; HCl = hydrogen chloride; HCOOH = formic acid; HPLC = high performance liquid chromatography; IPA = propan-2-ol; i-PrMgCl·LiCl = isopropylmagnesium chloride lithium chloride complex; K2CO3= potassium carbonate; KHMDS = potassium bis(trimethylsilyl)amide; KH2PO4= potassium dihydrogen phosphate; KI = potassium idodide; LiAlH4 = lithium aluminium hydride; LiCl = lithium chloride; M = molar; MeMgBr = methylmagnesium bromide; MeNH2 = methylamine; MeOH = methanol; 2-Me-TFH = 2- methyltetrahydrofuran; mg = milligram(s); MgSO4= magnesium sulfate; min = minute(s); mL = milliliter; mm = millimeter(s); mmHg = millimeter(s) of mercury; MS = mass spectrometry; Ms2O = methanesulfonic anhydride; MTBE = 2-methoxy-2-methylpropane; m / z = mass-to-charge ratio; NaBH3CN = sodium cyanoborohydride; NaBH4= sodium borohydride; NaHSO4= sodium hydrogen sulfate; NaNO2= sodium nitrite; NaOAc = sodium acetate; Na2SO4= sodium sulfate; NH4Cl = ammonium chloride; nm = nanometer(s); PE = petroleum ether; Pd / C = palladium on carbon; Pd2(dba)3= tris(dibenzylideneacetone)dipalladium; Pd(OAc)2= Palladium(II) acetate; (PPh3)2PdCl2·DCM = bis(triphenylphosphine)palladium chloride dichloromethane solvate; ppm = part(s) per million; RP = reverse phase; RuPhos = 2-dicyclohexylphosphino-2′,6′- diisopropoxybiphenyl; SFC = supercritical fluid chromatography; SiO2 = silicon dioxide; SOCl2 = thionyl chloride;tBuOH = tert-butanol; TEA = trimethylamine; THF = tetrahydrofuran; Ti(OiPr)4 = Titanium isopropoxide; tR = retention time; Xantphos = (9,9-dimethyl-9H-xanthene- 4,5-diyl)bis(diphenylphosphane); µL = microliter(s), µm = micrometer(s). The present compounds of general formula (I) where U = O or S and V = covalent bond or C(RV)2 can be prepared starting from an intermediate of formula 1 as shown in Scheme 1. Intermediate 1 can be activated with a coupling agent such as CDT (U = O) or 1,1'-thiocarbonyldiimidazole (U = S) in the presence of a base (e.g. TEA, DIPEA) in a solvent such as DMF, DCM or CH3CN to generate the activated intermediate 2 in situ. Addition of intermediate 3 to the reaction mixture generates compounds of general formula (I). In some instances, intermediate 2 can be isolated, and then converted to the corresponding urea using the above-mentioned reaction conditions. Furthermore, the order of addition can be interconverted and in some instances, intermediates of formula 3 can be activated first, and amines of formula 1 added in a second time to the reaction mixture. A person skilled in the art will recognize that when amines of formula 1 are not commercially available, they can be prepared via a Curtius rearrangement from the corresponding carboxylic acids, using standard reaction conditions. Scheme 1 The building blocks of general formula 1 are commercially available or can be prepared via methods known to the person skilled in the art. Building blocks of general formula 3 can be obtained commercially or can be prepared via methods known to the person skilled in the art (e.g. reductive amination from the corresponding ketone or aldehyde and amine or using Ellman-type chemistry followed by a reduction or an alkylation step). Alternatively, amines of general formula 3 where R1= CH2OH, X = C, R2a, R2b= hydrogen, C1- C6-alkyl and R3= C1-C6-alkyl or C3-C10-cycloalkyl, depicted as compound 4 in Scheme 2, can be prepared starting from suitably protected aryl bromide 5. Ester 6 can be prepared via carbonylation of bromide 5 using a palladium catalyst in the presence of a base such as TEA and MeOH, in a carbon monoxide atmosphere. Hydroxymethyl intermediate 7 can be prepared from ester 6 using standard reaction conditions such as LiAlH4in a polar aprotic solvent such as THF. Deprotection of the amine using conditions known to a person skilled in the art affords amines of general formula 4. Scheme 2 Alternatively, amines of general formula 3 where L = covalent bond, A = 3- to 14-membered heterocyclyl, R1a= H, halogen, C1-C6-alkyl, X = C, R2a, R2b= hydrogen, C1-C6-alkyl and R3= C1- C6-alkyl or C3-C10-cycloalkyl, depicted as compound 8 in Scheme 3, can be prepared from suitably protected commercially available bromides 5. Buchwald-Hartwig cross-coupling of bromides 5 with commercially available amines 9 using a Pd-catalyst such as Pd2(dba)3 in the presence of a ligand such as Xantphos and a base such as but no limited to Cs2CO3at elevated temperatures in a polar aprotic solvent such as 1,4-dioxane followed by deprotection affords amines of general formula 8. A person skilled in the art will recognize that amines 8 can be prepared using alternative methods such as SNAr or Chan-Lam couplings. Scheme 3 Alternatively, amines of general formula 3 where L = covalent bond, A = 5- to 14-membered heteroaryl, C6-C10-aryl and C3-C10-cycloalkyl, R1a= H, halogen, C1-C6-alkyl, X = C, R2a, R2b= hydrogen, C1-C6-alkyl and R3= C1-C6-alkyl or C3-C10-cycloalkyl, depicted as compound 10 in Scheme 3, can be prepared from suitably protected commercially available bromides 5. Suzuki- Miyaura cross-coupling of bromides 5 with commercially available potassium trifluoroborates 11 using a Pd-catalyst such as Pd(OAc)2in the presence of a ligand such as RuPhos or catalytic systems such as CataCXium Pd G4 and a base such as but no limited to KH2PO4 or Cs2CO3 at elevated temperatures in toluene and water followed by deprotection affords amines of general formula 10. A person skilled in the art will recognize that potassium trifluoroborates 11 can be replaced by the corresponding boronic acids or pinacol boronic esters. A person skilled in the art will also recognize that the electrophiles and nucleophiles can be interchanged depending on the substitutents, leading to the same compound 10. Scheme 4 Alternatively, amines of general formula 3 where R2a= hydrogen, R2b= hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, C1-C6-alkoxy, halo-C1-C6-alkoxy, C1-C6-alkyl-NH-C1-C6-alkyl-, C3-C10- cycloalkyl, and R2c-O-C1-C6-alkyl, depicted as compound 12 in Scheme 5, can be prepared from the corresponding commercially available ketone (when R2b= C1-C6-alkyl, halo-C1-C6-alkyl, C1- C6-alkoxy, halo-C1-C6-alkoxy, C1-C6-alkyl-NH-C1-C6-alkyl-, C3-C10-cycloalkyl, and R2c-O-C1- C6-alkyl) or aldehydes (when R2b= hydrogen) 13. Treatment of 13 with an amine R3NH2 (14) in a polar protic solvent such as 2-propanol or EtOH followed by reduction of the in situ generated imine by a reducing agent such as NaBH4or sodium triacetoxyborohydride affords amines of general formula 12. In some instances, Ti(OiPr)4 can be added to help imine formation. A person skilled in the art will recognize that ketones of general formula 13 can be prepared using standard chemistry starting from the corresponding bromide (e.g. but not limited to Grignard reaction or Weinreb ketone synthesis). Scheme 5 Alternatively, amines of general formula 3 where L = NH, A = 3- to 14-membered heterocyclyl, R1a= H, halogen, C1-C6-alkyl, X = C, R2a, R2b= hydrogen, C1-C6-alkyl and R3= C1-C6-alkyl or C3-C10-cycloalkyl, depicted as compound 15 in Scheme 6, can be prepared from suitably protected commercially available bromides 5. Buchwald-Hartwig cross-coupling of suitably protected bromides 5 with commercially available amines 16 using a Pd-catalyst such as Pd2(dba)3 or Pd(OAc)2 in the presence of a ligand such as Xantphos or 2,2'-bis(diphenylphosphino)-1,1'- binaphthyl and a base such as but no limited to Cs2CO3at elevated temperatures in solvent such as 1,4-dioxane or toluene followed by deprotection affords amines of general formula 15. A person skilled to the art will recognize that amines 15 can be prepared using alternative methods such as SNAr or Chan-Lam couplings. Scheme 6 Alternatively, amines of general formula 3 where R2a= hydrogen, R2b= hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, C1-C6-alkoxy, halo-C1-C6-alkoxy, C1-C6-alkyl-NH-C1-C6-alkyl-, C3-C10- cycloalkyl, and R2c-O-C1-C6-alkyl, depicted as compound 12 in Scheme 7, can be prepared from the corresponding commercially available ketones (when R2b= C1-C6-alkyl, halo-C1-C6-alkyl, C1- C6-alkoxy, halo-C1-C6-alkoxy, C1-C6-alkyl-NH-C1-C6-alkyl-, C3-C10-cycloalkyl, and R2c-O-C1- C6-alkyl) or aldehydes (when R2b= hydrogen) 13. Treatment of building block 13 with a reducing agent such as as NaBH4 or sodium triacetoxyborohydride affords alcohols of general formula 17. Conversion of the alcohol to a better leaving group with e.g. but not limited to MeSO2Cl followed by substitution with an amine 14 in the presence of a base such as DIPEA or TEA gives amines of general formula 12. A person skilled in the art will recognize that when not commercially available, ketones of general formula 13 can be prepared using standard chemistry starting from the corresponding bromide (e.g. but not limited to Grignard reaction or Weinreb ketone synthesis). Scheme 7 Amines of general formula 1 where V = covalent bond, R4a= R4b= R5a= R5b= R6b= R7= hydrogen, R6a= 5- to 14-membered heteroaryl and C6-C10-aryl, depicted as compound 18 in Scheme 8, can be prepared starting from aldehyde 19. Treatment of aldehyde 19 with methyl-4- chlorobutyrate in THF followed by NaOtBu affords the corresponding tetrahydrofuran 20. Tetrahydrofuran 20 can be converted to the corresponding amine 18 via a Curtius rearrangement, e.g. using TEA, tert-butanol and diphenylphosphoric azide at 80 °C followed by deprotection. 1. Curtius rearrangement 2. Deprotection 19 20Scheme 8 Compounds of general formula (I) where U = N-CN, depicted as compound 21 in Scheme 9, can be prepared starting from thiourea 22. Thiourea 22 can be prepared as described in Scheme 1. Methylation of 22 with MeI followed by NH3 in MeOH affords thioethers 23. Treatment of thioethers 23 with cyanamide in the presence of a base such as DIPEA in THF give compounds of general formula 21. 2223 21Scheme 9 Alternatively, amines of general formula 3 where L = CH2and A = C3-C10-cycloalkyl, depicted as compound 24 in Scheme 10, can be prepared from suitably protected commercially available bromides 5. Suzuki-Miyaura cross-coupling of bromides 5 with commercially available pinacol esters 25 using a Pd-catalyst such as Pd(OAc)2in the presence of a ligand such as RuPhos or catalytic systems such as CataCXium Pd G4 and a base such as but no limited to KH2PO4 or Cs2CO3 at elevated temperatures in toluene and water affords alkenes 26. Hydrogenation of alkenes 26 using Pd / C under hydrogen atmosphere in EtOAc gives compounds of general formula 24. If not commercially available, pinacol esters 25 can be prepared as reported by Kovalenko et al., EJOC 2019, 33, 5624-5635). Scheme 10 Alternatively, amines of general formula 3 where R2a= hydrogen, depicted as compound 3 in Scheme 11, can be prepared starting from commercially available aldehydes 27. Aldehydes 27 can be treated with a Grignard reagent to give secondary alcohols 17. Alcohols 17 can be treated with SOCl2 to generate the corresponding chlorides 28. Chlorides 28 can be substituted by amines 14 in the presence of a base such as K2CO3, optionally in the presence of an additive such as KI, in a polar solvent such as but not limited to DMF, to give amines of general formula 12. If not commercially available, aldehydes 27 can be prepared from the corresponding heterocycles or halides using methods known to a person skilled in the art. Similarly, alcohols of formula 17 can be converted to other leaving groups such as bromides or mesylates using standard methods. Scheme 11 Alternatively, amines of general formula 3 where R2a= hydrogen and R2b= C6-C10-aryl-C1-C6- alkyl and C = heteroaromatic ring optionally substituted with 1-2 halogen substituents, depicted as compound 29 in Scheme 12, can be prepared starting from homobenzylic aldehyde of general formula 30. Treatment of aldehyde 30 with 4-methylbenzenesulfonohydrazide (31) in MeOH at 60 °C generates compounds of general formula 32. Treatment of 32 with aldehyde 27 in the presence of a base such as Cs2CO3 in a polar aprotic solvent such as 1,4-dioxane at elevated temperatures gives ketones 33. Condensation of amine 14 with ketone 33 in THF, optionally in the presence of an acid such as acetic acid, followed by reduction of the imine generated in situ (e.g. using but not limited to NaBH3CN), generates amines of general formula 29. Scheme 12 Alternatively, amines of general formula 3 where R2a= H and R2b= halo-C1-C6-alkyl, depicted as compound 12 in Scheme 13, can be prepared starting from esters of general formula 34. Esters 34 yield alkylation products 35 upon treatment with LDA and a trifluoromethyl sulfonate 36, at -40 °C in THF. Treatment of esters 35 with hydrazine in EtOH at elevated temperatures gives hydrazides 37. Hydrazides 37 give carbamates 38 in a Curtius rearrangement, upon treatment with an acid such as HCl, followed by NaNO2, water, and tBuOH. Carbamates 38 can be alkylated with an alkylating agent R3-X (X = halide) and a base such as but not limited to NaH in a polar aprotic solvent such as THF, giving carbamates 39. Deprotection of 39 gives amines of general formula 12. Scheme 13 Alternatively, amines of general formula 3 where R3= halo-C1-C6-alkyl can be prepared from benzylic amines 40 (Scheme 14). Treatment of amines 40 with (2,5-dioxopyrrolidin-1-yl) formate (41) in THF followed by addition of a base such as TEA gives formamides 42. Treatment of formamides 42 with Lawesson’s reagent, followed by TEA and H2O, gives thioformamides 43. Treatment of thioformamides 43 with AgOCF3gives amines of general formula 3. Scheme 14 Alternatively, amines of general formula 3 can be prepared starting from commercially available benzylic amines 40 (Scheme 15). Amines 40 can be protected (e.g. but not limited to Boc) using standard conditions, to generate protected amines 44. Alkylation of such amines 44 using a base (e.g. NaH or KHMDS) and a methylating agent R3-X (X = halide) gives tertiary amines 45. Deprotection using standard conditions lead to amines of general formula 3. If not commercially available, benzylic amines 40 can be prepared using techniques known to a person skilled in the art. Scheme 15 Alternatively, amines of general formula 3 where R2a= hydrogen and R2b= R2c-O-C1-C6-alkyl, depicted as compound 46 in Scheme 16, can be prepared starting from commercially available phenols 47. Treatment of phenols 47 with acetyl bromides 48 and a base such as K2CO3 in a polar aprotic solvent such as MeCN generate ethers 49. Ethers 49 can be converted to amines of general formula 46 via reductive amination, using standard reaction conditions (e.g. NaOAc or TEA as a base and NaNH3CN as reducing agent). Scheme 16 Alternatively, compounds of general formula (I) where U = O, V = covalent bond, A = 3- to 14- membered heterocyclyl, 5- to 14-membered heteroaryl, or C6-C10-aryl, depicted as compound 50 in Scheme 17, can be generated from compounds of general formula 51. Bromides of general formula 51 can be prepared as described in Scheme 1. Suzuki-Miyaura cross-coupling between bromides 51 and commercially available pinacol esters 52 using a catalyst such as cataCXium Pd G4 and a base such as Cs2CO3in 1,4-dioxane / H2O affords to compounds of general formula 50. A person skilled in the art should recognize that alternative aryl halides could be used for the cross- coupling, such as aryl chlorides or aryl iodides. Scheme 17 Alternatively, compounds of general formula (I) where R1= C2-C6-alkynyl, depicted as compound 53 in Scheme 18, can be prepared from bromides 51. Bromides 51 can be coupled with alkynes 54 in a Sonogashira cross-coupling using e.g. CuI, bis(triphenylphosphine)palladium(II) chloride, TEA in THF, to give the alkyne-containing compounds of general formula 53. Scheme 18 Alternatively, compounds of general formula (I) where A = 3- to 14-membered heterocyclyl, 5- to 14-membered heteroaryl, or C6-C10-aryl, depicted as compound 50 in Scheme 19, can be prepared from bromides 51. Bromides 51 can be coupled with commercially available stannanes 55 in a Stille cross-coupling, using e.g. LiCl, Pd(PPh3)4 in 1,4-dioxane at elevated temperatures, to give compounds of general formula 51. If not commercially available, stannanes 55 can be prepared using methods known to the person skilled in the art. Scheme 19 In one aspect, the present invention provides a process of manufacturing a compound of formula (Ia) described herein, or a pharmaceutically acceptable salt thereof comprising: reacting a first amine 1, wherein R4a, R4b, R5a, R5b, R6a, R6b, and R7are as defined herein, 1 with a second amine 3, wherein R1, R2a, R2b, R3, X, Y, and Z are as defined herein, in the presence of a base and a urea forming reagent, to form said compound of formula (Ia). In one embodiment, said base is selected from TEA, DIPEA and sodium bicarbonate. In a preferred embodiment, said base is selected from TEA and DIPEA. In a particularly preferred embodiment, said base is selected DIPEA. In one embodiment, said urea forming reagent is selected from bis(trichloromethyl) carbonate, phosgene, trichloromethyl chloroformate, (4-nitrophenyl)carbonate, 1,1’-carbonyl-di-imidazole, and 1,1’-Carbonyl-di-(1,2,4-triazole). In a preferred embodiment, said urea forming reagent is 1,1’-Carbonyl-di-(1,2,4-triazole). In one aspect, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, when manufactured according to any one of the processes described herein. SARM1 Inhibitory Activity Compounds of the present invention are SARM1 inhibitors. Thus, in one aspect, the present invention provides the use of compounds of formula (I) as described herein for inhibiting the function of human SARM1 in a subject in need thereof. In a further aspect, the present invention provides compounds of formula (I) as described herein for use in a method of inhibiting the function of human SARM1 in a subject in need thereof. In a further aspect, the present invention provides the use of compounds of formula (I) as described herein for the preparation of a medicament for inhibiting the function of human SARM1 in a subject in need thereof. In a further aspect, the present invention provides a method for inhibiting the function of human SARM1 in a subject in need thereof, which method comprises administering an effective amount of a compound of formula (I) as described herein to the subject. SARM1 inhibitory potency of the compounds of formula (I) according to the invention was measured using the following assay. Enzymatic reactions were ran in a 10µL volume consisting of 8nM human SARM1 (aa28-724), 100µM Nicotinamide (NMN) and 30µM Nicotinamide Adenine Dinculeotide (NAD). Assay reagents were prepared in 25mM HEPES pH 7.2, 50mM NaCl, 1mM EDTA and 0.0025% Tween20. To determine compound IC50’s, reactions were incubated for 60minutes at room temperature in the presence of a 12-point concentration response curve of compound (starting concentration 100µM; 1 in 3 dilution between each point; 2% DMSO) and then quenched with 40µL of 0.125% Formic Acid. The peak area of NAD and linear ADPR were measured by a RapidFire High Throughput Mass Spectrometry System (Agilent Technologies, Santa Clara, CA) using an API5000 triple quadrupole mass spectrometer (AB Sciex Framingham, MA). The ratio of linear ADPR to NAD peak area was then plotted against compound concentration to obtain an IC50 as fitted via non-linear regression. SARM1 inhibitory potencies of the compounds of formula (I) according to the invention as measured in the assay described above are presented in Table 1. Table 1 Example IC50 hSARM1 Example IC50 hSARM1 [µM] [µM] 1 2.335 21 0.689 2 2.341 22 1.783 3 2.210 23 0.262 4 3.904 24 2.805 5 2.998 25 1.126 6 0.892 26 1.873 7 1.425 27 0.328 8 3.617 28 0.822 9 0.343 29 2.366 10 4.235 30 0.373 11 0.442 31 5.008 12 0.529 32 2.355 13 1.135 33 1.074 14 7.295 34 0.762 15 1.394 35 0.539 16 1.289 36 4.704 17 0.544 37 1.070 18 0.520 38 3.612 19 0.708 39 7.541 20 6.260 40 4.386 Example IC50 hSARM1 Example IC50 hSARM1 [µM] [µM] 41 3.489 62 5.611 42 1.895 63 2.363 43 7.485 64 2.565 44 0.671 65 0.730 45 2.753 66 5.939 46 4.902 67 1.084 47 2.351 68 1.232 48 1.024 69 2.722 49 0.385 70 3.155 50 4.498 71 1.215 51 7.784 72 1.260 52 1.861 73 9.991 53 5.912 74 1.540 54 5.631 75 3.199 55 2.767 76 1.145 56 7.088 77 0.263 57 0.619 78 9.115 58 0.977 79 5.297 59 7.217 80 0.991 60 2.536 81 4.612 61 4.127 82 3.292 Using the Compounds of the Invention In one aspect, the present invention provides a compound of formula (I), or a pharmaceutically acceptable salt thereof, as described herein for use as a therapeutically active substance. In a further aspect, the present invention provides a method of treating or preventing a condition associated with SARM1 in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition described herein. In a further aspect, the present invention provides a compound of formula (I) described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition described herein, for use in a method of treating or preventing a condition associated with SARM1 in a subject in need thereof. In a further aspect, the present invention provides the use of a compound of formula (I) described herein, or of a pharmaceutically acceptable salt thereof, or of a pharmaceutical composition described herein, in a method of treating or preventing a condition associated with SARM1 in a subject in need thereof. In a further aspect, the present invention provides the use of a compound of formula (I) described herein, or of a pharmaceutically acceptable salt thereof, in the preparation of a medicament for use in a method of treating or preventing a condition associated with SARM1 in a subject in need thereof. In one embodiment, said condition associated with SARM1 is a condition affecting the nervous system, including the central nervous system and the peripheral nervous system. In one embodiment, said condition affecting the nervous system is neurodegenerative disorder. In one embodiment, said condition associated with SARM1 is selected from amyotrophic lateral sclerosis, spinal muscular atrophy, chemotherapy induced peripheral neuropathy, diabetes induced peripheral neuropathy, multiple sclerosis, Parkinson's disease, glaucoma, stroke, traumatic brain injury, and Charcot-Marie-Tooth disease. In a preferred embodiment, said condition associated with SARM1 is selected from amyotrophic lateral sclerosis, spinal muscular atrophy, chemotherapy induced peripheral neuropathy, diabetes induced peripheral neuropathy, and multiple sclerosis. In a particularly preferred embodiment, said condition associated with SARM1 is amyotrophic lateral sclerosis. In a particularly preferred embodiment, said condition associated with SARM1 is spinal muscular atrophy. In a particularly preferred embodiment, said condition associated with SARM1 is chemotherapy induced peripheral neuropathy. In a particularly preferred embodiment, said condition associated with SARM1 is diabetes induced peripheral neuropathy. In a particularly preferred embodiment, said condition associated with SARM1 is multiple sclerosis. Pharmaceutical Compositions and Administration In one aspect, the present invention provides a pharmaceutical composition comprising a compound of formula (I) as described herein and a therapeutically inert carrier. In one embodiment, there is provided a pharmaceutical composition according to Example 83 or 84. The compounds of formula (I) and their pharmaceutically acceptable salts can be used as medicaments (e.g. in the form of pharmaceutical preparations). The pharmaceutical preparations can be administered internally, such as orally (e.g. in the form of tablets, coated tablets, dragées, hard and soft gelatin capsules, solutions, emulsions or suspensions), nasally (e.g. in the form of nasal sprays) or rectally (e.g. in the form of suppositories). However, the administration can also be effected parentally, such as intramuscularly or intravenously (e.g. in the form of injection solutions). The compounds of formula (I) and their pharmaceutically acceptable salts can be processed with pharmaceutically inert, inorganic or organic adjuvants for the production of tablets, coated tablets, dragées and hard gelatin capsules. Lactose, corn starch or derivatives thereof, talc, stearic acid or its salts etc. can be used, for example, as such adjuvants for tablets, dragées and hard gelatin capsules. Suitable adjuvants for soft gelatin capsules are, for example, vegetable oils, waxes, fats, semi- solid substances and liquid polyols, etc. Suitable adjuvants for the production of solutions and syrups are, for example, water, polyols, saccharose, invert sugar, glucose, etc. Suitable adjuvants for injection solutions are, for example, water, alcohols, polyols, glycerol, vegetable oils, etc. Suitable adjuvants for suppositories are, for example, natural or hardened oils, waxes, fats, semi- solid or liquid polyols, etc. Moreover, the pharmaceutical preparations can contain preservatives, solubilizers, viscosity- increasing substances, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavorants, salts for varying the osmotic pressure, buffers, masking agents or antioxidants. They can also contain still other therapeutically valuable substances. The dosage can vary in wide limits and will, of course, be fitted to the individual requirements in each particular case. In general, in the case of oral administration 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), divided into preferably 1-3 individual doses, which can consist, for example, of the same amounts, should be appropriate. It will, however, be clear that the upper limit given herein can be exceeded when this is shown to be indicated. Examples The invention will be more fully understood by reference to the following examples. The claims should not, however, be construed as limited to the scope of the examples. In case the preparative examples are obtained as a mixture of enantiomers, the pure enantiomers can be separated by methods described herein or by methods known to the man skilled in the art, such as e.g., chiral chromatography (e.g., chiral SFC) or crystallization. The compounds of formula I can contain several asymmetric centers and can be present in the form of optically pure enantiomers, mixtures of enantiomers such as, for example, racemates, optically pure diastereoisomers or mixtures of diastereoisomers. According to the Cahn-Ingold- Prelog Convention the asymmetric carbon atom can be of the "R" or "S" configuration. For the compounds described in the patent the absolute stereochemistry was arbitrarily assigned. The relative configuration at the tetrahydrofuran ring can be either cis or trans and was assigned arbitrarily. All reaction examples and intermediates were prepared under an argon atmosphere if not specified otherwise. The compounds disclosed and described herein have been named using the IUPAC naming function of Biovia Draw 22.1. Where more than one name is associated with a Formula (I) compound or intermediate, the chemical structure shall define the compound. Example 1 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(3RS)-tetrahydrofuran-3-yl]urea To a solution of tetrahydrofuran-3-ylamine; hydrochloride (CAS RN: 204512-94-7; 45.37 mg, 367.13 µmol) in DMF (734.27 µL) was added DIPEA (192.36 µL, 1.1 mmol) followed by CDT (66.28 mg, 403.85 µmol). The mixture was stirred at 50 °C for 1 h, before being treated with methyl-[(1S)-1-(4-pyridyl)ethyl]amine (CAS RN: 42732-16-1; 50 mg, 367.13 µmol). The mixture was stirred at 70 °C for 20 h, before being poured into 2-Me-THF and washed with water and brine. The organic layer was dried over Na2SO4and evaporated. Purification by FC (SiO2; DCM / MeOH) and chiral SFC (Column chiral OZ-H, 5 µm, 250x20 mm, 25% EtOH) gave the title compound as a mixture of diastereomers (39.8 mg, 43%, tR = 2.485 min) and as a colorless oil. MS (ESI): m / z = 250.2 [M+H]+Example 2 1-methyl-3-[(3RS, 4RS or 3RS,4SR)-4-methyltetrahydrofuran-3-yl]-1-[(1S)-1-(4- pyridyl)ethyl]urea To a solution of (4-methyltetrahydrofuran-3-yl)amine (CAS RN: 1527863-66-63; 7.14 mg, 367.13 µmol) in DMF (734.27 µL) was added DIPEA (192.36 µL, 1.1 mmol) followed by CDT (66.28 mg, 403.85 µmol). The mixture was stirred at room temperature for 30 min before being treated with methyl-[(1S)-1-(4-pyridyl)ethyl]amine (CAS RN: 42732-16-1; 50 mg, 367.13 µmol). The mixture was stirred at 70 °C for 30 min before being poured into 2-Me-THF and washed with water and brine. The organic layer was dried over Na2SO4and evaporated. Purification by HPLC (Gemini NX, 12 nm, 5 µm, 100 x 30 mm, 40 mL / min, MeOH / H2O+0.1% TEA) gave the title compound (20.3 mg, 20%, tR = 2.017 min) as a white oil. MS (ESI): m / z = 264.1 [M+H]+Example 3 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(3RS)-3-(trifluoromethyl)tetrahydrofuran-3-yl]urea To a solution of [3-(trifluoromethyl)tetrahydrofuran-3-yl]amine;hydrochloride (CAS RN: 1638269-35-8, 68 mg, 354.94 µmol, ) in DCM (860 µL) was added DIPEA (220 µL, 1.29 mmol) followed by CDT (75 mg, 456.97 µmol). The mixture was stirred at room temperature for 1 h. Then, methyl-[(1S)-1-(4-pyridyl)ethyl]amine (CAS RN: 42732-16-1; 48 mg, 50 µL, 352.45 mmol) was added and the reaction mixture was stirred at room temperature for 16 h. The reaction mixture was extracted with DCM. The organic layers were washed with water and brine. The combined organic layers were dried over Na2SO4 and evaporated. Purification by FC (SiO2; DCM / MeOH) gave the title compound as a mixture of diastereomers (67 mg, 57%) and as an off-white solid. MS (ESI): m / z = 318.1 [M+H]+Example 4 3-[(3RS)-3-(1H-imidazol-2-yl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea To a solution of [3-(1H-imidazol-2-yl)tetrahydrofuran-3-yl]amine;dihydrochloride (CAS RN 2031269-25-5, 99.61 mg, 440.56 µmol) in DMF (881.12 uL) was added DIPEA (230.83 µL, 1.32 mmol) followed by CDT (79.54 mg, 484.62 µmol). The mixture was stirred at 50 °C for 1 h, before being treated with methyl-[(1S)-1-(4-pyridyl)ethyl]amine (CAS RN: 42732-16-1; 60 mg, 440.56 µmol). The resulting mixture was heated up at 75°C for 20 h before being poured into 2-Me-THF and washed with water and brine. The organic layer was dried over Na2SO4and evaporated. Purification by HPLC (Gemini NX, 12 nm, 5μm, 100x30mm, CH3CN / H2O) gave the title compound as a mixture of diastereomers (9.2 mg, 6%) and as a colorless oil. MS (ESI): m / z = 316.1 [M+H]+Example 5 1-methyl-3-[(3RS)-3-(1-methylpyrazol-4-yl)tetrahydrofuran-3-yl]-1-[(1S)-1-(4- pyridyl)ethyl]urea To a solution of [rac-(2S,3R)-2-(1-methylpyrazol-4-yl)tetrahydrofuran-3- yl]amine;dihydrochloride (CAS RN 1807941-18-9; 88.16 mg, 367.13 µmol) in DMF (734.27 µL) was added DIPEA (192.36 µL, 1.1 mmol) followed by CDT (66.28 mg, 403.85 µmol). The mixture was stirred at 75 °C for 30 min, before being treated with methyl-[(1S)-1-(4-pyridyl)ethyl]amine (CAS RN: 42732-16-1; 50 mg, 367.13 µmol). The mixture was heated up at 70 °C for 30 min before being poured into 2-Me-THF and washed with water and brine. The organic layer was dried over Na2SO4and evaporated. Purification by HPLC (Gemini NX, 12 nm, 5 µm, 100x30 mm, CH3CN / H2O+0.1% HCOOH) gave the title compound as a mixture of diastereomers (70.9 mg, 53%) and as a white viscous oil. MS (ESI): m / z = 330.2 [M+H]+Example 6 3-[(2RS,3SR)-2-(5-bromo-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea To a solution of [rac-(2S,3R)-2-(5-bromo-3-pyridyl)tetrahydrofuran-3-yl]amine;dihydrochloride (CAS RN: 1955553-29-3; 116.02 mg, 367.13 µmol) in DMF (734.27 µL) was added DIPEA (142.35 mg, 192.36 µL, 1.1 mmol) followed by CDT (66.28 mg, 403.85 µmol). The mixture was stirred at 75 °C for 30 min, before being treated with methyl-[(1S)-1-(4-pyridyl)ethyl]amine (CAS RN: 42732-16-1; 50 mg, 367.13 µmol). The mixture was heated up at 70 °C for 30 min before being poured into 2-Me-THF and washed with water and brine. The organic layer was dried over Na2SO4and evaporated. Purification by HPLC (Gemini NX, 12 nm, 5 µm, 100 x 30 mm, 40 mL / min, CH3CN / H2O+0.1% HCOOH) gave the title compound as a mixture of diastereomers (80.2 mg, 53%) and as an off-white viscous oil. MS (ESI): m / z = 405.1 [M+H]+Example 7 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(2RS,3SR)-2-[5-(3-pyridyl)-3-pyridyl]tetrahydrofuran- 3-yl]urea To a solution of [rac-(2S,3R)-2-[5-(3-pyridyl)-3-pyridyl]tetrahydrofuran-3- yl]amine;trihydrochloride (CAS RN: 2241139-77-3; 128.74 mg, 367.13 µmol) in DMF (734.27 µL) was added DIPEA (192.36 µL, 1.1 mmol) followed by CDT (66.28 mg, 403.85 µmol). The mixture was stirred at 75 °C for 30 min, before being treated with methyl-[(1S)-1-(4- pyridyl)ethyl]amine (CAS RN: 42732-16-1; 50 mg, 367.13 µmol). The mixture was heated up at 70 °C for 30 min before being poured into 2-Me-THF and washed with water and brine. The organic layer was dried over Na2SO4 and evaporated. Purification by HPLC (Gemini NX, 12 nm, 5 µm, 100 x 30 mm, 40 mL / min, CH3CN / H2O+0.1% HCOOH) gave the title compound as a mixture of diastereomers (107 mg, 71%) and as a white solid. MS: (ESI): m / z = 404.2 [M+H]+ Example 8 3-[(2RS,3SR)-2-(5-cyclopropyl-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea To a solution of [rac-(2S,3R)-2-(5-cyclopropyl-3-pyridyl)tetrahydrofuran-3- yl]amine;dihydrochloride (CAS RN: 2241140-72-5; 59 mg, 212.85 µmol) in DMF (350 µL) was added DIPEA (0.140 µL, 817.84 µmol) followed by CDT (39 mg, 237.62 µmol). The mixture was stirred at 50 °C for 1 hour, before being treated with methyl-[(1S)-1-(4-pyridyl)ethyl]amine (CAS RN: 42732-16-1; 28.8 mg, 30 µL, 211.47 µmol). The mixture was heated up at 70 °C for 30 min before being poured into EtOAc and 5% aq. LiCl-H2O solution. The aqueous layer was back- extracted with EtOAc. The organic layers were washed three times with 5% aq. LiCl-solution, once with water and once with brine. The organic layers were dried over Na2SO4and evaporated. Purification by FC (SiO2; DCM / MeOH) gave the title compound as a mixture of diastereomers (43 mg, 53%) and as an off-white solid. MS (ESI): m / z = 367.2 [M+H]+Example 9 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea or 3-[(3S)- 4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 58.58 mg, 367.13 µmol) in DMF (734.27 uL) was added DIPEA (192.36 µL, 1.1 mmol) followed by CDT (66.28 mg, 403.85 µmol). The mixture was stirred at 75 °C for 30 min before being treated with methyl-[(1S)-1-(4-pyridyl)ethyl]amine (CAS RN: 42732-16-1; 50 mg, 367.13 µmol). The mixture was heated up at 75 °C for 1 h before being poured into 2-Me-THF and washed with water and brine. The organic layer was dried over Na2SO4and evaporated. Purification by HPLC (Gemini NX, 12 nm, 5 µm, 100x30 mm, MeOH / H2O+0.1% TEA) gave the title compound (20.6 mg, 19%, tR= 1.993 min) as colorless oil. MS(ESI): m / z = 286.1 [M+H]+Example 10 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea or 3-[(3R)- 4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 58.58 mg, 367.13 µmol) and DIPEA (192.36 µL, 1.1 mmol) in DMF (734.27 uL) were added CDT (66.28 mg, 403.85 µmol). The mixture was stirred at 75 °C for 30 min before being treated with methyl-[(1S)-1-(4-pyridyl)ethyl]amine (CAS RN: 42732-16-1; 50 mg, 367.13 µmol). The mixture was heated up at 75 °C for 1 h before being poured into 2-Me-THF and washed with water and brine. The organic layer was dried over Na2SO4and evaporated. Purification by HPLC (Gemini NX, 12 nm, 5 µm, 100x30 mm, MeOH / H2O+0.1% TEA) gave the title compound (23.2 mg, 21%, tR = 2.048 min) as colorless oil. MS(ESI): m / z = 286.1 [M+H]+Example 11 3-[(2S,3R)-2-(5-bromo-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea or 3-[(2R,3S)-2-(5-bromo-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)- 1-(4-pyridyl)ethyl]urea Starting from 92 mg of Example 6: 3-[(2RS,3SR)-2-(5-bromo-3-pyridyl)tetrahydrofuran-3-yl]-1- methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea , chiral SFC (Column chiral IA, 5 µm, 250x20 mm, 25% MeOH) gave the title compound (3.8 mg, 2%, tR = 2.549 min) and as a yellow viscous oil. MS (ESI): m / z = 405.1 [M+H]+ Example 12 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(2R,3S)-2-[5-(3-pyridyl)-3-pyridyl]tetrahydrofuran-3- yl]urea or 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(2S,3R)-2-[5-(3-pyridyl)-3- pyridyl]tetrahydrofuran-3-yl]urea Starting from 52.6 mg of Example 7: 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(2RS,3SR)-2-[5-(3- pyridyl)-3-pyridyl]tetrahydrofuran-3-yl]urea, chiral SFC (Column chiral Lux C4, 5 µm, 250x20 mm, 40%MeOH) gave the title compound (21.8 mg, 39%, tR= 3.746 min) and as a yellow viscous oil. MS (ESI): m / z = 404.2 [M+H]+Example 13 3-[(2R,3S)-2-(5-cyclopropyl-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea or 3-[(2S,3R)-2-(5-cyclopropyl-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1- [(1S)-1-(4-pyridyl)ethyl]urea Starting from 30 mg of Example 8: 3-[(2RS,3SR)-2-(5-cyclopropyl-3-pyridyl)tetrahydrofuran-3- yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea, chiral SFC (Column chiral Lux C4, 5 µm, 250x20 mm, 30% MeOH) gave the title compound (13.4 mg, 42%, tR = 2.601 min) and as a colorless oil. MS (ESI): m / z = 367.3 [M+H]+Example 14 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-(2,2,2-trifluoro-1-tetrahydrofuran-3-yl-ethyl)urea To a solution of (2,2,2-trifluoro-1-tetrahydrofuran-3-yl-ethyl)amine (CAS RN: 1342056-79-4; 37.26 mg, 220.28 µmol) in DMF (300 µL) was added DIPEA (76.94 µL, 440.56 µmol) followed by CDT (52.22 mg, 286.36 µmol). The mixture was stirred at 50 °C for 1 h, before being treated with methyl-[(1S)-1-(4-pyridyl)ethyl]amine (CAS RN: 42732-16-1; 30 mg, 31.25 µL, 220.28 µmol). The mixture was heated up at 70 °C for 16 h before being poured into 2-Me-THF and washed with water and brine. The organic layers were dried over Na2SO4 and evaporated. Purification by RP-HPLC gave the title compound as a diasteromeric mixture (39 mg, 51% yield) and as a colorless amorphous solid. MS (ESI): m / z = 332.2 [M+H]+Example 15 1-[(3-chloro-4-pyridyl)methyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 20 mg, 125.34 µmol) in DMF (200 µL) was added DIPEA (109.46 µL, 626.72 µmol) followed by CDT (29.71 mg, 162.95 µmol). The mixture was stirred at 50 °C for 1 h, before being treated with (3-chloro-4-pyridyl)methyl-methyl-amine;dihydrochloride (CAS RN: 2270911-80-1; 31.65 mg, 137.88 µmol). The mixture was heated up at 70 °C for 16 h. Purification by RP-HPLC gave the title compound as a racemic mixture (24 mg, 60% yield) and as an off-white solid. MS (ESI): m / z = 306.1 [M+H]+Example 16 3-(4,4-difluorotetrahydrofuran-3-yl)-1-[(3-fluoro-4-pyridyl)methyl]-1-methyl-urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 20 mg, 125.34 µmol) in DMF (200 µL) was added DIPEA (109.46 µL, 626.72 µmol) followed by CDT (29.71 mg, 162.95 µmol). The mixture was stirred at 50 °C for 1 h, before being treated with (3-fluoro-4-pyridyl)methyl-methyl-amine;dihydrochloride (CAS RN: 2460754-71-4; 26.71 mg, 125.34 µmol). The mixture was heated up to 80 °C for 16 h, before being cooled down. Purification by RP-HPLC gave the title compound as a racemic mixture (24 mg, 63% yield) and as a white solid. MS (ESI): m / z = 290.2 [M+H]+Example 17 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-(4-pyridylmethyl)urea To a solution of 4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 17 mg, 106.54 µmol) in DMF (170 µL) was added DIPEA (55.82 µL, 319.63 µmol) followed by CDT (25.26 mg, 138.51 µmol). The mixture was stirred at 50 °C for 1 h, before being treated with methyl(4-pyridylmethyl)amine (CAS RN: 6971-44-4; 13.02 mg, 106.54 µmol). The mixture was heated up at 80 °C for 16 h. Purification by RP-HPLC gave the title compound as a racemic mixture (10 mg, 33% yield) and as a colorless amorphous solid. MS (ESI): m / z = 272.2 [M+H]+Example 18 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)propyl]urea or 3-[(3S)- 4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-(4-pyridyl)propyl]urea or 3-[(3R)-4,4- difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)propyl]urea or 3-[(3R)-4,4- difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-(4-pyridyl)propyl]urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 86 mg, 538.98 µmol) in DCM (1.2 mL) was added DIPEA (0.320 mL, 1.87 mmol) followed by CDT (113 mg, 688.5 µmol). The reaction mixture was stirred at 23 °C for 1 h before being treated with a solution of methyl(4-pyridylmethyl)amine (CAS RN: 6971-44-4; 80 mg, 532.55 µmol) in DCM (0.200 mL). The mixture was stirred at 23 °C for 3 h before being poured into DCM and washed with water and brine. The aqueous layer was backextracted twice with DCM. The organic layers were dried over Na2SO4and evaporated. Purification by FC (SiO2, heptane / EtOAc) gave two diastereomers A (70 mg) and B (57 mg). Starting from 70 mg of diasteromers A, chiral SFC (Column chiral Wrr C4, 5 µm, 250x20 mm, 15% MeOH) gave the title compound (30 mg, 18%, tR= 4.280 min) as an off white solid. MS (ESI): m / z = 300.3 [M+H]+Example 19 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[(3-methyl-4-pyridyl)methyl]urea To a solution of 4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 90 mg, 564.05 µmol) in DMF (800 µL) was added DIPEA (246.28 µL, 1.41 mmol) followed by CDT (133.72 mg, 733.27 µmol). The mixture was stirred at 50 °C for 1 h, before being treated with methyl-[(3-methyl-4-pyridyl)methyl]amine (CAS RN: 915919-59-4; 76.82 mg, 564.05 µmol). The mixture was heated up at 70 °C for 1 h. Purification by RP-HPLC gave the title compound as a racemic mixture (117 mg, 69% yield) and as a colorless amorphous solid. MS (ESI): m / z = 286.2 [M+H]+Example 20 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyridazin-4-ylethyl]urea or 3- [(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyridazin-4-ylethyl]urea or 3- [(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyridazin-4-ylethyl]urea or 3- [(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyridazin-4-ylethyl]urea To a solution of 4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 75.94 mg, 475.96 µmol) in DMF (952 µL) was added DIPEA (498.76 µL, 2.86 mmol) followed by CDT (85.93 mg, 523.56 µmol). The mixture was stirred at 50 °C for 1 h, before being treated with methyl(1-pyridazin-4-ylethyl)amine;dihydrochloride (CAS RN: 2913244-09-2; 100 mg, 475.96 µmol). The mixture was heated up at 70 °C for 2 h before being poured into 2-Me-THF and washed with water and brine. The organic layers were dried over Na2SO4and evaporated. Purification by FC (SiO2, DCM / MeOH) gave the title compound as a diasteromeric mixture (92 mg, 68% yield) and as white solid. MS (ESI): m / z 287.1 [M+H]+Starting from 92 mg of diasteromeric mixture, chiral SFC (Column chiral Whelk(r,r), 5 µm, 250x20 mm, 25% EtOH) gave the title compound (12.8 mg, 9% yield, tR= 2,572 min) as a white solid. MS (ESI): m / z = 287.1 [M+H]+Example 21 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyridazin-4-ylethyl]urea or 3- [(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyridazin-4-ylethyl]urea or 3- [(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyridazin-4-ylethyl]urea or 3- [(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyridazin-4-ylethyl]urea To a solution of 4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 75.94 mg, 475.96 µmol) in DMF (952 µL) was added DIPEA (498.76 µL, 2.86 mmol) followed by CDT (85.93 mg, 523.56 µmol). The mixture was stirred at 50 °C for 1 h, before being treated with methyl(1-pyridazin-4-ylethyl)amine;dihydrochloride (CAS RN: 2913244-09-2; 100 mg, 475.96 µmol). The mixture was heated up at 70 °C for 2 h before being poured into 2-Me-THF and washed with water and brine. The organic layers were dried over Na2SO4and evaporated. Purification by FC (SiO2, DCM / MeOH) gave the title compound as a diasteromeric mixture (92 mg, 68% yield) and as white solid. MS (ESI): m / z = 287.1 [M+H]+Starting from 92 mg of diasteromeric mixture, chiral SFC (Column chiral Whelk(r,r), 5 µm, 250x20 mm, 25% EtOH) gave the title compound (13 mg, 9%, tR = 3.038 min) as a colorless oil. MS (ESI): m / z = 287.1 [M+H]+Example 22 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyridazin-4-ylethyl]urea or 3- [(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyridazin-4-ylethyl]urea or 3- [(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyridazin-4-ylethyl]urea or 3- [(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyridazin-4-ylethyl]urea To a solution of 4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 75.94 mg, 475.96 µmol) in DMF (952 µL) was added DIPEA (498.76 µL, 2.86 mmol) followed by CDT (85.93 mg, 523.56 µmol). The mixture was stirred at 50 °C for 1 h, before being treated with methyl(1-pyridazin-4-ylethyl)amine;dihydrochloride (CAS RN: 2913244-09-2; 100 mg, 475.96 µmol). The mixture was heated up at 70 °C for 2 h before being poured into 2-Me-THF and washed with water and brine. The organic layers were dried over Na2SO4and evaporated. Purification by FC (SiO2, DCM / MeOH) gave the title compound as a diasteromeric mixture (92 mg, 68% yield) and as a white solid. MS (ESI): m / z = 287.1 [M+H]+Starting from 92 mg of diasteromeric mixture, chiral SFC (Column chiral Whelk(r,r), 5 µm, 250x20 mm, 25% EtOH) gave the title compound (14 mg, 10% yield, tR = 3.373 min) as a light yellow oil. MS (ESI): m / z = 287.1 [M+H]+Example 23 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-(4-pyridylmethyl)urea or 3-[(3R)-4,4- difluorotetrahydrofuran-3-yl]-1-methyl-1-(4-pyridylmethyl)urea To a solution of 4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 70 mg, 438.71 µmol) in DMF (700 µL) was added DIPEA (229.86 µL, 1.32 mmol) followed by CDT (104. mg, 570.32 µmol). The mixture was stirred at 50 °C for 1 h, before being treated with methyl(4-pyridylmethyl)amine (CAS RN: 6971-44-4; 53.6 mg, 438.71 µmol). The mixture was heated up at 80 °C for 1 h. Purification by HPLC (Gemini NX, 12 nm, 5 µm, 100x30 mm, ACN / H2O+0.1% TEA) gave the title compound as a racemic mixture (72 mg, 57% yield) and as a white solid. MS (ESI): m / z = 272.2 [M+H]+Starting from 72 mg of the racemic mixture, chiral SFC (Column chiral Whelk(r,r), 5 µm, 250x20 mm, 23% EtOH) gave the title compound (32 mg, 44% yield, tR= 2.265 min) as a light yellow. MS (ESI): m / z = 272.2 [M+H]+Example 24 3-(4-benzoyltetrahydrofuran-3-yl)-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea To a solution of (4-aminotetrahydrofuran-3-yl)-phenyl-methanone;hydrochloride (EN300- 1693205; 83.59 mg, 367.13 µmol) in DMF (734.27 µL) was added DIPEA (192.36 µL, 1.1 mmol) followed by CDT (66.28 mg, 403.85 µmol). The mixture was stirred at 75 °C for 30 min, before being treated with methyl-[(1S)-1-(4-pyridyl)ethyl]amine (CAS RN: 42732-16-1; 50 mg, 367.13 µmol). The mixture was heated up at 75 °C for 3 h before being poured into 2-Me-THF and washed with water and brine. The organic layer was dried over Na2SO4and evaporated. Purification by RP-HPLC gave the title compound as a diasteromeric mixture (33 mg, 24% yield) and as a colorless oil. MS (ESI): m / z = 354.3 [M+H]+Example 25 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(3R)-3-(trifluoromethyl)tetrahydrofuran-3-yl]urea or 1- methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(3S)-3-(trifluoromethyl)tetrahydrofuran-3-yl]urea Starting from 30.49 mg of Example 3: 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(3RS)-3- (trifluoromethyl)tetrahydrofuran-3-yl]urea, chiral SFC (Column chiral IC, 5 µm, 250x20 mm, 15% MeOH) gave the title compound (6.7 mg, 21% yield, tR= 3.717 min) and as a colorless oil. MS (ESI): m / z = 318.1 [M+H]+ Example 26 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(3R)-3-(trifluoromethyl)tetrahydrofuran-3-yl]urea or 1- methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(3S)-3-(trifluoromethyl)tetrahydrofuran-3-yl]urea Starting from 30.49 mg of Example 3: 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(3RS)-3- (trifluoromethyl)tetrahydrofuran-3-yl]urea, chiral SFC (Column chiral IC, 5 µm, 250x20 mm, 15% MeOH) gave the title compound (5.1 mg, 16% yield, tR = 4.155 min) and as a colorless oil. MS (ESI): m / z = 318.1 [M+H]+Example 27 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(3-methyl-4-pyridyl)methyl]urea or 3- [(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(3-methyl-4-pyridyl)methyl]urea Starting from 117 mg of Example 19: 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[(3- methyl-4-pyridyl)methyl]urea, chiral SFC (Column chiral Whelk(r,r), 5 µm, 250x20 mm, 25% MeOH) gave the title compound (54 mg, 46% yield, tR = 2.493 min) and as a colorless amorphous solid. MS (ESI): m / z = 286.1 [M+H]+Example 28 1-[(3-bromo-4-pyridyl)methyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea To a solution of 4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 500 mg, 3.13 mmol) in DMF (6.93 mL) was added DIPEA (2.53 mL, 14.51 mmol) followed by CDT (436.48 mg, 2.66 mmol). The mixture was stirred at 50 °C for 1 h, before being treated with methyl-[1-(3-bromo-4-pyridyl)ethyl-]amine (CAS RN: 463941-58-4; 453.63 mg, 2.26 mmol). The mixture was heated up at 70 °C for 16 h before being poured into 2-Me-THF and washed with water and brine. The organic layer was dried over Na2SO4and evaporated. Purification by FC (SiO2, heptane / EtOAc / EtOH) gave the title compound as a racemic mixture (358.7 mg, 31% yield) and as a light yellow gum. MS (ESI): m / z = 350.1 [M+H]+Example 29 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyrimidin-4-ylethyl]urea or 3- [(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyrimidin-4-ylethyl]urea or 3- [(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyrimidin-4-ylethyl]urea or 3- [(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyrimidin-4-ylethyl]urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 93.87 mg, 588.29 µmol) in DCM (5 mL) were added DIPEA (410.97 µL, 2.35 mmol) and CDT (115.86 mg, 705.94 µmol). The mixture was stirred at 23 °C for 1 h, before being treated with methyl-[1-(4-pyrimidyl)ethyl]amine;hydrochloride (102.15 mg, 588.29 µmol). The mixture was stirred at 23 °C over 15 h. The solvent was removed in vacuo. Purification by FC (SiO2, DCM / MeOH) gave the title compound as a diasteromeric mixture. Starting from the diasteromeric mixture, chiral SFC (Column chiral Whelk(r,r), 5 µm, 250x20 mm, 15% EtOH) gave the title compound (33 mg, 19% yield, tR = 3.983 min) as a colorless oil. MS (ESI): m / z = 287.3 [M+H]+Step a): N-methyl-1-pyrimidin-4-yl-ethanamine To a solution of 1-pyrimidin-4-ylethanone (CAS RN: 39870-05-8; 500.0 mg, 4.09 mmol) in DCE (2 mL) were added DIPEA (2.18 mL, 12.28 mmol) and MeNH2·HCl (822.89 mg, 12.28 mmol). The mixture was stirred at 50 °C for 1 h before being treated with sodium cyanoborohydride (771.8 mg, 12.28 mmol). The reaction was stirred at 50 °C for 12 h before being filtered off. The filtrate was washed with DCM and concentrated to give the title compound (1856.0 mg, 83% yield) as a dark green oil. MS (ESI): m / z = 138.1 [M+H]+Step b): tert-butyl N-methyl-N-(1-pyrimidin-4-ylethyl)carbamate To a solution of N-methyl-1-pyrimidin-4-yl-ethanamine (8150.0 mg, 11.88 mmol) in MeOH (40 mL) were added Boc2O (3889.6 mg, 17.82 mmol) and DIPEA (4.14 mL, 23.76 mmol). The mixture was stirred at 25 °C for 1 h. Purification by FC (SiO2, PE / EtOAc) gave the title compound (2324.0 mg, 82% yield) as a light yellow oil. MS (ESI): m / z = 182.1 [M-C4H8+H]+Step c): N-methyl-1-pyrimidin-4-yl-ethanamine;hydrochloride A solution of tert-butyl N-methyl-N-(1-pyrimidin-4-ylethyl)carbamate (2815.0 mg, 11.86 mmol) in dioxane / HCl (30.0 mL, 60.0 mmol) was stirred at 25 °C for 2 h. The precipitate was collected by filtration, washed by PE and dried under high vacuum to give the title compound (1.77 g, 80% yield) as a light brown solid. MS (ESI): m / z = 138.2 [M+H]+Example 30 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-fluoro-4-pyridyl)ethyl]-1-methyl-urea or 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-fluoro-4-pyridyl)ethyl]-1-methyl- urea or 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-fluoro-4-pyridyl)ethyl]-1- methyl-urea or 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-fluoro-4-pyridyl)ethyl]- 1-methyl-urea Starting from 127 mg of diasteromeric mixture (step d, 3-(4,4-difluorotetrahydrofuran-3-yl)-1-[1- (3-fluoro-4-pyridyl)ethyl]-1-methyl-urea), chiral SFC (Column chiral Whelk(r,r), 5 µm, 250x20 mm, 11% EtOH) gave the title compound (31 mg, 21% yield, tR= 2.071 min) as a colorless oil. MS (ESI): m / z = 304.3 [M+H]+Step a): 1-(3-fluoro-4-pyridyl)-N-methyl-ethanamine To a solution of 1-(3-fluoro-4-pyridyl)ethanone (2.0 g, 14.38 mmol) and MeNH2·HCl (2.9 g, 43.13 mmol) in DCE (20 mL) was added DIPEA (7.64 mL, 43.13 mmol). The mixture was stirred at 50 °C for 1h before being treated with sodium cyanoborohydride (2.7 g, 43.13 mmol). The mixture was stirred at 70 °C for 12h before being concentrated under reduced pressure to give the title compound (2.0 g, 90% yield) as a yellow oil which was used in the next step without any further purification. MS (ESI): m / z = 155.2 [M+H]+Step b): tert-butyl N-[1-(3-fluoro-4-pyridyl)ethyl]-N-methyl-carbamate To a solution of 1-(3-fluoro-4-pyridyl)-N-methyl-ethanamine (2 g, 12.97 mmol) in MeOH (20 mL) and TEA (1.3 g, 12.97 mmol) was added Boc2O (5662.62 mg, 25.94 mmol). The mixture was stirred at 25°C for 2 h before being concentrated under reduced pressure.Purification by FC (SiO2, PE / EtOAc) gave the title compound (1.2 g, 36% yield) as a yellow oil. MS (ESI): m / z = 255.1 [M+H]+Step c): 1-(3-fluoro-4-pyridyl)-N-methyl-ethanamine;dihydrochloride To a solution of tert-butyl N-[1-(3-fluoro-4-pyridyl)ethyl]-N-methyl-carbamate (1.2 g, 4.72 mmol) in 1,4-dioxane (2 mL) was added a solution of HCl in 1,4-dioxane (20.0 mL, 40.0 mmol) The mixture was stirred at 25 °C for 1 h before being filtered and the cake dried under reduced pressure to give the title compound (710.31 mg, 66% yield) as a yellow solid. MS (ESI): m / z = 155.2 [M+H]+Step d): 3-(4,4-difluorotetrahydrofuran-3-yl)-1-[1-(3-fluoro-4-pyridyl)ethyl]-1-methyl-urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 89 mg, 557.78 µmol) in DCM (1.4 mL) was added DIPEA (380 µL, 2.22 mmol) followed by CDT (117 mg, 712.87 µmol). The mixture was stirred at 23 °C for 1 h. Then, 1-(3-fluoro-4-pyridyl)- methyl-ethanamine;dihydrochloride (105 mg, 462.33 mmol) was added and the reaction mixture was stirred at 23 °C for 16 h. The reaction mixture was extracted with DCM. The organic layers were washed with water and brine. The aqueous layer was backextracted twice with DCM. The combined organic layers were dried over Na2SO4and evaporated. Purification by FC (SiO2; heptane / EtOAc) gave the title compound as a diasteromeric mixture (127 mg, 90% yield). Example 31 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-fluoro-4-pyridyl)ethyl]-1-methyl-urea or 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-fluoro-4-pyridyl)ethyl]-1-methyl- urea or 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-fluoro-4-pyridyl)ethyl]-1- methyl-urea or 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-fluoro-4-pyridyl)ethyl]- 1-methyl-urea Starting from 127 mg of diasteromeric mixture of Example 30, Step d (3-(4,4- difluorotetrahydrofuran-3-yl)-1-[1-(3-fluoro-4-pyridyl)ethyl]-1-methyl-urea), chiral SFC (Column chiral Whelk(r,r), 5 µm, 250x20 mm, 11% EtOH) gave the title compound (29 mg, 19%, tR= 2.250 min) as a colorless oil. MS (ESI): m / z = 304.3 [M+H]+Example 32 3-(4,4-difluorotetrahydrofuran-3-yl)-1-[[3-(hydroxymethyl)-4-pyridyl]methyl]-1-methyl-urea To a solution of 4,4-difluorotetrahydrofuran-3-amine;hydrochloride (CAS RN: 2408969-70-8; 90.0 mg, 0.56 mmol) and DIPEA (0.59 mL, 3.38 mmol) in DMF (1 mL) was added CDT (120.34 mg, 0.73 mmol). The mixture was stirred at 50 °C for 1 h, before being treated with [4- (methylaminomethyl)-3-pyridyl]methanol;dihydrochloride (126.97 mg, 0.56 mmol). The mixture was stirred for 2 h at 80 °C, and for 18 h at 23 °C. Purification by RP-HPLC gave the title compound (10.1 mg, 6% yield) as a colorless oil. MS (ESI): m / z = 302.2 [M+H]+Step a): tert-butyl N-[(3-bromo-4-pyridyl)methyl]-N-methyl-carbamate A solution of Boc2O (7163.92 mg, 32.82 mmol) was added dropwise to a stirred solution of 1-(3- bromo-4-pyridyl)-N-methyl-methanamine (CAS RN: 463941-58-4; 6.0 g, 29.84 mmol) in DCM (30 mL), at 25 °C. The mixture was stirred for 18 h at 23 °C before being evaporated, to give the title compound (9.0 g, 96% yield) as a light yellow oil. MS (ESI): m / z = 301.0 / 303.0 [M+H]+Step b): methyl 4-[[tert-butoxycarbonyl(methyl)amino]methyl]pyridine-3-carboxylate A mixture of tert-butyl N-[(3-bromo-4-pyridyl)methyl]-N-methyl-carbamate (4.0 g, 13.28 mmol), triethylamine (2.22 mL, 15.94 mmol), 1,1'-bis(diphenylphosphino)ferrocene- palladium(II)dichloride dichloromethane complex (325.12 mg, 0.4 mmol) and MeOH (800 mL) was stirred at 130 °C for 28 h under carbon monoxide atmosphere (15000 mmHg), before being cooled down and evaporated. The residue was diluted with EtOAc (100 mL) and washed with water (2x 50 mL). The organic layer was dried over Na2SO4, filtered and evaporated, to give the title compound (2.4 g, 59% yield). MS (ESI): m / z = 281.0 [M+H]+Step c): tert-butyl N-[[3-(hydroxymethyl)-4-pyridyl]methyl]-N-methyl-carbamate A solution of methyl 4-[[tert-butoxycarbonyl(methyl)amino]methyl]pyridine-3-carboxylate (500.0 mg, 1.78 mmol) in THF (5 mL) was added dropwise to a suspension of LiAlH4(54.15 mg, 1.43 mmol) in THF (5 mL), at 0 °C. The mixture was stirred for 2 h at 0 °C before being allowed to warm up to 23 °C. Water (0.06 mL), 15% aqueous sodium hydroxide solution (0.06 mL) and then water (0.2 mL) were added to the reaction mixture at 0 °C, which was stirred for 1 h at 23 °C. The precipiate was then filtered off. The filtrate was evaporated, to give the title compound (470.0 mg, 99% yield). MS (ESI): m / z = 253.2 [M+H]+Step d): [4-(methylaminomethyl)-3-pyridyl]methanol;dihydrochloride To a solution of tert-butyl N-[[3-(hydroxymethyl)-4-pyridyl]methyl]-N-methyl-carbamate (250.0 mg, 0.79 mmol) in DCM (4.44 mL) was added 4 M HCl in 1,4-dioxane (2.38 mL, 9.51 mmol). The mixture was stirred for 18 h at 23 °C, before being evaporated to give the title compound (130.0 mg, 73% yield) as a light yellow oil. MS (ESI): m / z = 153.2 [M+H]+ Example 33 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(3-methyl-4-pyridyl)ethyl]urea or 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-(3-methyl-4-pyridyl)ethyl]urea or 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(3-methyl-4- pyridyl)ethyl]urea or 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-(3-methyl- 4-pyridyl)ethyl]urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 46.91 mg, 293.97 µmol) in DMF (587.94 µL) was added DIPEA (308.05 µL, 1.76 mmol) followed by CDT (53.07 mg, 323.37 µmol). The mixture was stirred at 50 °C for 1 h, before being treated with methyl-[1-(3-methyl-4-pyridyl)ethyl]amine (CAS RN: 1550152-27-6; 55.2 mg, 293.97 µmol). The mixture was stirred for 15 h at 70 °C, before being poured into 2-Me-THF and washed with water and brine. The organic layer was dried over Na2SO4, filtered and evaporated. Purification by FC (SiO2; DCM / MeOH) and chiral SFC (Column chiral IF, 5 µm, 250 x 20 mm, 15% MeOH) gave the title compound (7.7 mg, 9% yield, tR = 1.27 min) as a colorless oil. MS (ESI): m / z = 300.3 [M+H]+Example 34 1-[(3-cyclopropyl-4-pyridyl)methyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea To a solution of 4,4-difluorotetrahydrofuran-3-amine;hydrochloride (CAS RN: 2408969-70-8; 68.75 mg, 0.43 mmol) and DIPEA (0.45 mL, 2.59 mmol) in DMF (0.625 mL) was added 1-(3- cyclopropyl-4-pyridyl)-N-methyl-methanamine;dihydrochloride (101.32 mg, 0.43 mmol), at 23 °C. The mixture was stirred at 50°C for 1 h, before being treated with 1-(3-cyclopropyl-4-pyridyl)- N-methyl-methanamine;dihydrochloride (101.32 mg, 0.43 mmol). The mixture was stirred for 2 h at 80 °C, before being cooled down. Purification by RP-HPLC gave the title compound (77.4 mg, 58% yield) as a yellow liquid. MS (ESI): m / z = 312.2 [M+H]+Step a): tert-butyl N-[(3-bromo-4-pyridyl)methyl]-N-methyl-carbamate A solution of Boc2O (7163.92 mg, 32.82 mmol) was added dropwise to a stirred solution of 1-(3- bromo-4-pyridyl)-N-methyl-methanamine (CAS RN: 463941-58-4; 6.0 g, 29.84 mmol) in DCM (30 mL) at 25 °C. The mixture was stirred for 18 h at 23 °C before being evaporated, to give the title compound (9.0 g, 96% yield) as a light yellow oil. MS (ESI): m / z = 301.0 / 303.0 [M+H]+Step b): tert-butyl N-[(3-cyclopropyl-4-pyridyl)methyl]-N-methyl-carbamate A solution of tert-butyl N-[(3-bromo-4-pyridyl)methyl]-N-methyl-carbamate (300.0 mg, 1.0 mmol) , potassium cyclopropyltrifluoroborate (515.9 mg, 3.49 mmol), tripotassium phosphate (634.32 mg, 2.99 mmol), and RuPhos (46.48 mg, 0.1 mmol) in toluene (4.8 mL) and water (1.2 mL) was degassed. Palladium(II) acetate (11.18 mg, 0.05 mmol) was added, and the mixture was stirred for 18 h at 100 °C in a sealed tube, before being cooled down. The mixture was diluted with EtOAc (50 mL), and washed with a saturated aqueous KH2PO4solution (50 mL). The organic layer was washed with brine (50 mL), dried over Na2SO4, filtered, and evaporated. Purification by RP-HPLC gave the title compound (174.1 mg, 67% yield) as a light yellow oil. MS (ES): m / z = 263.2 [M+H]+Step c): 1-(3-cyclopropyl-4-pyridyl)-N-methyl-methanamine;dihydrochloride To a solution of tert-butyl N-[(3-cyclopropyl-4-pyridyl)methyl]-N-methyl-carbamate (110.0 mg, 0.42 mmol) in DCM (2.44 mL) was added 4 M HCl in 1,4-dioxane (1.26 mL, 5.03 mmol). The mixture was stirred for 18 h at 23 °C, before being evaporated to give the title compound (98.0 mg, 99% yield) as a white solid. MS (ESI): m / z = 163.0 [M+H]+Example 35 1-[(3-bromo-4-pyridyl)methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-urea or 1- [(3-bromo-4-pyridyl)methyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-urea Starting from 162 mg of Example 28: 1-[(3-bromo-4-pyridyl)methyl]-3-(4,4- difluorotetrahydrofuran-3-yl)-1-methyl-urea, chiral SFC (Column chiral IF, 5 µm, 250x20 mm, 25% MeOH) gave the title compound (63 mg, 39% yield, tR= 1.553 min) as a colorless oil. MS (ESI): m / z = 350. [M+H]+Example 36 1-[[3-(azetidin-1-yl)-4-pyridyl]methyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea To a solution of 4,4-difluorotetrahydrofuran-3-amine;hydrochloride (CAS RN: 2408969-70-8; 46.0 mg, 0.29 mmol) and DIPEA (0.3 mL, 1.73 mmol) in DMF (0.50 mL) was added CDT (61.51 mg, 0.37 mmol). The mixture was stirred at 50 °C for 1 h, before being treated with 1-[3-(azetidin- 1-yl)-4-pyridyl]-N-methyl-methanamine;2,2,2-trifluoroacetic acid (149.72 mg, 0.29 mmol). The mixture was stirred for 2 h at 80 °C, before being cooled down. Purification by RP-HPLC gave the title compound (15.6 mg, 17% yield) as a yellow oil. MS (ESI): m / z = 327.2 [M+H]+Step a): tert-butyl N-[(3-bromo-4-pyridyl)methyl]-N-methyl-carbamate A solution of Boc2O (7163.92 mg, 32.82 mmol) was added dropwise to a stirred solution of 1-(3- bromo-4-pyridyl)-N-methyl-methanamine (CAS RN: 463941-58-4; 6.0 g, 29.84 mmol) in DCM (30 mL), at 25 °C. The mixture was stirred for 18 h at 23 °C before being evaporated, to give the title compound (9.0 g, 96% yield) as a light yellow oil. MS (ESI): m / z = 301.0 / 303.0 [M+H]+Step b): tert-butyl N-[[3-(azetidin-1-yl)-4-pyridyl]methyl]-N-methyl-carbamate A solution of tert-butyl N-[(3-bromo-4-pyridyl)methyl]-N-methyl-carbamate (300.0 mg, 1.0 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (57.64 mg, 0.1 mmol), tris(dibenzylideneacetone)dipalladium (0) (45.61 mg, 0.05 mmol), azetidine hydrochloride (279.55 mg, 2.99 mmol) and cesium carbonate (1947.26 mg, 5.98 mmol) in 1,4-dioxane (15 mL) was sparged with Ar, before being stirred for 18 h at 100 °C. The mixture was cooled down and filtered off. The filtrated was evaporated. Purification by RP-HPLC gave the title compound (72.2 mg, 26% yield) as a light yellow oil. MS (ESI): m / z = 278.2 [M+H]+Step c): 1-[3-(azetidin-1-yl)-4-pyridyl]-N-methyl-methanamine;2,2,2-trifluoroacetic acid To a solution of tert-butyl N-[[3-(azetidin-1-yl)-4-pyridyl]methyl]-N-methyl-carbamate (85.0 mg, 0.31 mmol) in DCM (2 mL) was added trifluoroacetic acid (0.12 mL, 1.53 mmol). The mixture was stirred for 18 h at 23 °C before being evaporated, to give the title compound (150.0 mg, 90% yield) as a light yellow oil. MS (ESI): m / z = 178.0 [M+H]+Example 37 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[2-phenoxy-1-(4-pyridyl)ethyl]urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (34.96 mg, 219.07 µmol) in dichloromethane (1100 µL) was added DIPEA (250 µL, 1.46 mmol) followed by CDT (46.61 mg, 283.97 µmol). The mixture was stirred for 1 h at 23 °C, before being treated with methyl-[2- phenoxy-1-(4-pyridyl)ethyl]amine (50 mg, 219.02 µmol). The mixture was stirred for 16 h at 23 °C, before being evaporated. Purification by RP-HPLC gave the title compound (14.7 mg, 18% yield) as a white powder. MS (ESI): m / z = 378.3 [M+H]+Step a): N-methyl-2-phenoxy-1-(4-pyridyl)ethanamine Titanium isopropoxide (2.1 mL, 7.09 mmol) was added at 0 °C over 2-5 min to a solution of 2- phenoxy-1-(4-pyridyl)ethanone (CAS RN: 1574141-85-7; 1440.0 mg, 6.75 mmol) in 2-propanol (9.65 mL). Then, methylamine ethanol (2.52 mL, 20.26 mmol) was added, and the mixture was allowed to warm up to 23 °C and stirred for another 18 h at this temperature, before being cooled down to 0 °C. Sodium borohydride (383.2 mg, 10.13 mmol) was added portionwise, and the mixture was stirred at 0 °C for 1 h before being diluted with EtOAc (2 mL) and brine (2 mL). The mixture was stirred for 10 min at 23 °C, before being filtered through celite. The organic layer was washed with brine, dried over Na2SO4, filtered, and evaporated. Purification by FC (SiO2; DCM / MeOH 9:1) gave the title compound (550 mg, 36% yield) as a yellow oil. MS (ESI): m / z = 229.2 [M+H]+Example 38 3-(4,4-difluorotetrahydrofuran-3-yl)-1-[2-methoxy-1-(4-pyridyl)ethyl]-1-methyl-urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 42.71 mg, 267.69 µmol) in dichloromethane (1 mL) was added DIPEA (305.48 µL, 1.78 mmol) followed by CDT (56.95 mg, 346.99 µmol). The mixture was stirred for 1 h at 23 °C, before being treated with 2-methoxy-1-(4-pyridyl)ethanol (75 mg, 267.63 µmol). The mixture was stirred for another 16 h at 23 °C before being evaporated. Purification by RP-HPLC gave the title compound (15 mg, 17% yield) as a light yellow solid. MS (ESI): m / z = 316.2 [M+H]+Step a): 2-methoxy-1-(4-pyridyl)ethanone To a solution of 4-bromopyridine (CAS RN: 1120-87-2; 6.5 g, 41.14 mmol) in THF (70 mL) was added dropwise i-PrMgCl·LiCl in THF (79.11 mL, 102.85 mmol), at -20 °C under N2atmosphere. The mixture was stirred for 1 h at this temperature, before being treated with N,2-dimethoxy-N- methyl-acetamide (CAS RN: 132289-57-7; 13.7 g, 102.85 mmol) in THF (15 mL). The mixture was stirred for 1 h at 0 °C, before being quenched with 30 mL of saturated aqueous NH4Cl. and poured into water. The mixture was extracted with EtOAc, and the combined organic layers were washed with brine, dried over Na2SO4, filtered, and evaporated. Purification by FC (SiO2; PE / EtOAc 1:1) gave the title compound (5.0 g, 80% yield) as a colorless oil.1H NMR (400 MHz, CDCl3) δ = 8.85 - 8.76 (m, 2H), 7.77 - 7.66 (m, 2H), 4.67 (s, 2H), 3.50 ppm (s, 3H). Step b): 2-methoxy-1-(4-pyridyl)ethanol To a solution of 2-methoxy-1-(4-pyridyl)ethanone (3.0 g, 19.85 mmol) in MeOH (30 mL) at 0 °C was added NaBH4(1.5 g, 39.69 mmol). The mixture was stirred for 2 h at 23 °C, before being evaporated. Purification by FC (SiO2; PE / EtOAc) gave the title compound (1.5 g, 49% yield) as a yellow oil. MS (ESI): m / z = 154.4 [M+H]+Step c): [2-methoxy-1-(4-pyridyl)ethyl] methanesulfonate A solution of 2-methoxy-1-(4-pyridyl)ethanol (1.5 g, 9.79 mmol) in DCM (15 mL) and TEA (6.79 mL, 48.96 mmol) at 0°C was added Ms2O (5.1 g, 29.38 mmol). The mixture was stirred for 12 h at 25°C, before being evaporated. Purification by FC (SiO2; PE / EtOAc) gave the title compound (1.0 g, 44% yield) as a yellow oil. MS (ESI): m / z = 232.1 [M+H]+Step d): 2-methoxy-N-methyl-1-(4-pyridyl)ethanamine A solution of [2-methoxy-1-(4-pyridyl)ethyl] methanesulfonate (1.0 g, 4.32 mmol) in 2 M MeNH2 solution in THF (32.43 mL, 64.86 mmol). The mixture was stirred for 12 h at 70 °C, before being evaporated, giving the crude title compound (846.0 mg, 82% yield) as a yellow oil. MS (ESI): m / z = 167.2 [M+H]+Example 39 3-(4,4-difluorotetrahydrofuran-3-yl)-1-[(3-methoxy-4-pyridyl)methyl]-1-methyl-urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 30 mg, 188.02 µmol) and DIPEA (82 µL, 469.51 µmol) in DCM (450 µL) was treated with CDT (45 mg, 246.77 µmol). The mixture was stirred for 1 h at 23 °C, before being treated with (3- methoxy-4-pyridyl)methyl-methyl-amine (29 mg, 190.55 µmol). The mixture was stirred for 16 h at 23 °C, before being poured into EtOAc (10 mL). The mixture was washed three times with water and brine. The aqueous layers were back-extracted with EtOAc (20 mL). The combined organic layers were dried over Na2SO4, filtered, and evaporated. Purification by FC (SiO2; heptane / EtOAc / MeOH) gave the title compound (33.5 mg, 56% yield) as a white powder. MS (ESI): m / z = 302.2 [M+H]+Step a): (3-methoxy-4-pyridyl)methyl-methyl-amine To a solution of 3-methoxyisonicotinaldehyde (CAS RN: 1849-52-1; 100 mg, 729.18 µmol) and methylamine hydrochloride (247 mg, 3.66 mmol) in MeOH (2 mL) was added sodium triacetoxyborohydride (473 mg, 2.23 mmol). The mixture was stirred for 18 h at 23 °C, before being treated with 2 M HCl (2 mL) and evaporated. The residue was dissolved in 2 M NaOH. The aqueous phase was extracted with DCM, and the combined organic layers were dried over Na2SO4, filtered, and evaporated, to give the crude title compound (60 mg, 52% yield) as a light yellow liquid. MS (ESI): m / z = 153.2 [M+H]+Example 40 1-[1-(3-chloro-4-pyridyl)ethyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 38.53 mg, 241.49 µmol) in DCM (599.38 µL) was added DIPEA (144.65 µL, 845 µmol) followed by CDT (59.44 mg, 362.14 µmol). The mixture was stirred for 1 h at 23 °C, before being treated with 1-(3-chloro-4-pyridyl)-N-methyl-ethanamine;dihydrochloride (50 mg, 241.43 µmol) and stirred for another 16 h at 23 °C. The mixture was extracted with DCM and water. The aqueous layer was back-extracted twice with DCM. The organic layers were washed with brine. The combined organic layers were dried over sodium sulfate, filtered and evaporated. Purification by RP-HPLC gave the title compound (22.4 mg, 28% yield) as a white oil. MS (ESI): m / z = 320.1 [M+H]+Step a): tert-butyl N-[1-(3-chloro-4-pyridyl)ethyl]-N-methyl-carbamate A mixture of 1-(3-chloro-4-pyridyl)-N-methyl-ethanamine (CAS RN: 1602674-56-5; 2194.0 mg, 12.86 mmol), Boc2O (4.2 g, 19.29 mmol) in MeOH (60 mL) was stirred for 1 h at 25 °C, before being evaporated. Purification by FC (SiO2; PE / EtOAc) gave the title compound (2.0 g, 57% yield) as a colorless oil. MS (ESI): m / z = 271.0 [M+H]+Step b): 1-(3-chloro-4-pyridyl)-N-methyl-ethanamine;dihydrochloride A solution of tert-butyl N-[1-(3-chloro-4-pyridyl)ethyl]-N-methyl-carbamate (1.0 g, 3.69 mmol) in 2 M HCl in 1,4-dioxane (30.0 mL, 60.0 mmol) was stirred for 4 h at 23 °C. The resulting precipitate was filtered, and the cake was dissolved in MeOH (40 mL), before being evaporated to give the title compound (812.1 mg, 90% yield) as a light yellow solid. MS (ESI): m / z = 171.1 [M- 2 HCl + H]+Example 41 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[(3-pyrrolidin-1-yl-4-pyridyl)methyl]urea To a solution of 4,4-difluorotetrahydrofuran-3-amine;hydrochloride (CAS RN: 2408969-70-8; 265.0 mg, 1.66 mmol) and DIPEA (1.74 mL, 9.96 mmol) in DMF (3.13 mL) was added CDT (354.35 mg, 2.16 mmol). The mixture was stirred at 50 °C for 1 h, before being treated with N- methyl-1-(3-pyrrolidin-1-yl-4-pyridyl)methanamine;trihydrochloride (499.32 mg, 1.66 mmol). The mixture was heated to 80 °C and stirred for 2 h at this temperature, before being cooled down. Purification by RP-HPLC gave the title compound (53.8 mg, 9% yield) as a yellow oil. MS (ESI): m / z = 341.4 [M+H]+Step a): tert-butyl N-[(3-bromo-4-pyridyl)methyl]-N-methyl-carbamate A solution of Boc2O (7163.92 mg, 32.82 mmol) was added dropwise to a stirred solution of 1-(3- bromo-4-pyridyl)-N-methyl-methanamine (CAS RN: 463941-58-4; 6.0 g, 29.84 mmol) in DCM (30 mL), at 25 °C. The mixture was stirred for 18 h at 23 °C before being evaporated, to give the title compound (9.0 g, 96% yield) as a light yellow oil. MS (ESI): m / z = 301.0 / 303.0 [M+H]+Step b): tert-butyl N-methyl-N-[(3-pyrrolidin-1-yl-4-pyridyl)methyl]carbamate A solution of tert-butyl N-[(3-bromo-4-pyridyl)methyl]-N-methyl-carbamate (1.6 g, 5.31 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (153.7 mg, 0.27 mmol), tris(dibenzylideneacetone)dipalladium (0) (243.23 mg, 0.27 mmol), pyrrolidine (1133.46 mg, 15.94 mmol) and cesium carbonate (5.19 g, 15.94 mmol) in 1,4-dioxane (80 mL) was stirred for 18 h at 100 °C. Purification by FC (SiO2; MTBE / MeOH) gave the title compound (500.0 mg, 32% yield) as a light yellow oil. MS (ESI): m / z = 292.2 [M+H]+Step c): N-methyl-1-(3-pyrrolidin-1-yl-4-pyridyl)methanamine;trihydrochloride To a solution of tert-butyl N-methyl-N-[(3-pyrrolidin-1-yl-4-pyridyl)methyl]carbamate (500.0 mg, 1.72 mmol) in DCM (10 mL) was added a solution of 4 M HCl in 1,4-dioxane (5.15 mL, 20.59 mmol). The mixture was stirred for 18 h at 23 °C before being evaporated, to give the title compound (500.0 mg, 87% yield) as a light yellow solid. MS (ESI): m / z = 192.0 [M+H]+Example 42 1-[(S)-cyclopropyl(4-pyridyl)methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-urea or 1-[(S)-cyclopropyl(4-pyridyl)methyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl- urea or 1-[(R)-cyclopropyl(4-pyridyl)methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea or 1-[(R)-cyclopropyl(4-pyridyl)methyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3- yl]-1-methyl-urea 1-[Cyclopropyl(4-pyridyl)methyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea (52.0 mg, 0.17 mmol) was separated by chiral SFC (Column CHIRALCEL OJ-H5, 5 µm, 250x20 mm, hexane:IPA:MeOH 90:5:5) to give the title compound (6.3 mg, 12% yield, tR = 0.695 min) as a colorless oil. MS (ESI): m / z = 312.2 [M+H]+Step a): 1-cyclopropyl-N-methyl-1-(4-pyridyl)methanamine A solution of cyclopropyl(4-pyridyl)methanone (CAS RN: 39512-48-6; 900.0 mg, 6.11 mmol) and monomethylamine in THF (20% wt, 1.81 mL, 9.17 mmol) in THF (10 mL) was cooled down to 0°C, before being treated dropwise with titanium(IV) isopropylate (2.61 g, 9.17 mmol). The mixture was stirred for 16 h at 23 °C, before before being cooled down to 0 °C and treated with sodium borohydride (462.69 mg, 12.23 mmol). The mixture was stirred for 16 h before being treated with MeOH (10 mL) and sodium borohydride (102.82 mg, 2.72 mmol) at 0°C. The reaction was stirred for another 2 h at 23 °C, before being treated with ice-cold water. The mixture was extracted with EtOAc, and the combined organic layers were dried over Na2SO4, filtered, and evaporated, to give the title compound (800.0 mg, 57% yield) as a light yellow oil. MS (ESI): m / z = 163.0 [M+H]+Step b): 1-[cyclopropyl(4-pyridyl)methyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea To a solution of 4,4-difluorotetrahydrofuran-3-amine;hydrochloride (CAS RN: 2408969-70-8; 50.0 mg, 0.31 mmol) and DIPEA (0.14 mL, 0.78 mmol) in DMF (0.500 mL) was added CDT (66.86 mg, 0.41 mmol), at 23 °C. The mixture was stirred for 1 h at 50 °C, before being treated with 1-cyclopropyl-N-methyl-1-(4-pyridyl)methanamine (101.68 mg, 0.31 mmol). The mixture was stirred for 2 h at 80 °C and for 18 h at 23 °C. Purification by RP-HPLC gave the title compound (28.0 mg, 27% yield) as a light brown oil. MS (ESI): m / z = 312.2 [M+H]+Example 43 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[1-(4-pyridyl)cyclopropyl]urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (36.08 mg, 226.11 µmol) (CAS RN: 2408969-70-8) in dichloromethane (452.22 µL) was added DIPEA (96.43 mg, 130.32 µL, 746.17 µmol) followed by CDT (55.66 mg, 339.17 µmol). The mixture was stirred at 23°C for 1 h, before being treated with methyl-[1-(4-pyridyl)cyclopropyl]amine;dihydrochloride (CAS RN: 2416728-56-6; 50 mg, 226.11 µmol). The mixture was stirred for 48 h at 23 °C, before being extracted with 2-Me-THF. The organic layers were washed with water and brine. The combined organic layers were dried over Na2SO4 and evaporated. Purification by RP-HPLC gave the title compound (29.3 mg, 41% yield) as a white oil. MS (ESI): m / z = 298.3 [M+H]+Example 44 3-[(2R,3S)-2-(5-bromo-2-methyl-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea or 3-[(2S,3R)-2-(5-bromo-2-methyl-3-pyridyl)tetrahydrofuran-3-yl]-1- methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea A suspension of (2R,3S)-2-(5-bromo-2-methyl-3-pyridyl)tetrahydrofuran-3- amine;dihydrochloride (62.0 mg, 0.19 mmol) in DCM (2 mL) was cooled down to 0 °C, before being treated with triethylamine (0.1 mL, 0.75 mmol) and CDT (33.51 mg, 0.21 mmol). The mixture was stirred for 1 h at this temperature, and (1S)-N-methyl-1-(4-pyridyl)ethanamine (CAS RN: 42732-16-1; 25.59 mg, 0.19 mmol) was added. The mixture was stirred at 20 °C for 15 h and concentrated. Purification by RP-HPLC gave 50.5 mg of racemic mixture. Purification by chiral SFC (Column: CHIRALPAK IС, 250x21 mm, 5 µm, hexane:IPA:MeOH 70:15:15, 18 mL / min) gave the title compound (16.1 mg, 20% yield, tR= 24.47 min) as a light brown solid. MS (ESI): m / z = 419.0 / 421.0 [M+H]+Step a): (2S,3S)-2-(5-bromo-2-methyl-3-pyridyl)tetrahydrofuran-3-carboxylic acid A solution of 5-bromo-2-methyl-pyridine-3-carbaldehyde (CAS RN: 1211532-24-9; 250.0 mg, 1.25 mmol) and methyl 4-chlorobutyrate (CAS RN: 3153-37-5; 187.75 mg, 1.37 mmol) in THF (3 mL) was cooled down to -30 °C, before being treated with sodium tert-butoxide (180.16 mg, 1.87 mmol). The mixture was stirred for 1 h at this temperature, before being warmed up to 25 °C and stirred for another 15 h. The mixture was evaporated and dissolved in MeOH (2 mL). A solution of potassium hydroxide (105.18 mg, 1.87 mmol) in water (2 mL) was added. The resulting mixture was stirred for 2 h at 23 °C, before being evaporated. The residue was dissolved in water (2 mL), and the aqeous layer was extratcted with MTBE. The aqueous layer was separated and acidified with saturated aqueous NaHSO4 solution to pH=4. The mixture was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and evaporated, to give the crude title compound (260.0 mg, 55% yield) as a white solid. MS (ESI): m / z = 286.0 / 288.0 [M+H]+Step b): tert-butyl N-[(2R,3S)-2-(5-bromo-2-methyl-3-pyridyl)tetrahydrofuran-3-yl]carbamate To a solution of (2S,3S)-2-(5-bromo-2-methyl-3-pyridyl)tetrahydrofuran-3-carboxylic acid (260.0 mg, 0.91 mmol) and triethylamine (0.19 mL, 1.36 mmol) in tert-butanol (7.8 mL, 82.19 mmol) was added diphenylphosphonic azide (0.2 mL, 0.91 mmol) dropwise, at 23 °C. The mixture was heated at 80 °C for 15 h and evaporated. The residue was dissolved in EtOAc, and the solution was washed with water. The organic layer was dried over sodium sulfate, filtered, and evaporated. Purification by FC (SiO2; hexane / EtOAc 3:1) gave the title compound (110.0 mg, 33% yield) as a white solid. MS (ESI): m / z = 356.7 / 358.7 [M+H]+Step c): (2R,3S)-2-(5-bromo-2-methyl-3-pyridyl)tetrahydrofuran-3-amine;dihydrochloride To a solution of tert-butyl N-[(2R,3S)-2-(5-bromo-2-methyl-3-pyridyl)tetrahydrofuran-3- yl]carbamate (72.0 mg, 0.2 mmol) in DCM (2 mL) was added 4 M HCl in 1,4-dioxane (0.5 mL, 10.0 eq). The mixture was stirred at 20 °C for 15 h, before being evaporated to give the crude title compound (64.0 mg, 96% yield) as a white solid. MS (ESI): m / z = 257.0 / 259.0 [M+H]+ Example 45 1-[(1S)-1-(3-chloro-4-pyridyl)ethyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-urea or 1-[(1S)-1-(3-chloro-4-pyridyl)ethyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl- urea or 1-[(1R)-1-(3-chloro-4-pyridyl)ethyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea or 1-[(1R)-1-(3-chloro-4-pyridyl)ethyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]- 1-methyl-urea or Starting from 22.4 mg of Example 40: 1-[1-(3-chloro-4-pyridyl)ethyl]-3-(4,4- difluorotetrahydrofuran-3-yl)-1-methyl-urea, chiral SFC (chiral Whelk(r,r), 12 nm, 5 µm, 250 x 20 mm, W(r,r) 80 mL 18% EtOH) gave the title compound (0.95 mg, 5% yield, tR= 2.11 min) as a white oil. MS (ESI): m / z = 320.1 [M+H]+Example 46 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[1-(4-pyridyl)cyclopropyl]urea or 3- [(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[1-(4-pyridyl)cyclopropyl]urea Starting from 40.0 mg of Example 43: 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[1-(4- pyridyl)cyclopropyl]urea, chiral SFC (chiral Whelk(r,r), 5 µm, 250 x 20 mm, 30% MeOH) gave the title compound (8.0 mg, 40% yield, tR= 2.15 min) as a white oil. MS (ESI): m / z = 298.1 [M+H]+ Example 47 1-[[3-(3-chloroanilino)-4-pyridyl]methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl- urea or 1-[[3-(3-chloroanilino)-4-pyridyl]methyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 48.44 mg, 303.57 µmol) in DCM (940 µL) was added DIPEA (212.07 µL, 1.21 mmol), followed by the addition of CDT (59.79 mg, 364.28 µmol) at 23 °C. The mixture was stirred for 1 h at 23 °C, before being treated with a solution of [3-(3-chloroanilino)-4-pyridyl]methyl-methyl-amine (75.2 mg, 303.57 µmol) in DCM (940 µL). The mixture was stirred for another 1.5 h at 23 °C, before being treated with water and evaporated. Purification by FC (SiO2; DCM / MeOH) followed by chiral SFC (Column chiral AD-H, 5 µm, 250 x 20 mm, 18% MeOH) gave the title compound (24.4 mg, 22% yield) as a white solid. MS (ESI): m / z = 397.3 [M+H]+Step a): tert-butyl N-[(3-bromo-4-pyridyl)methyl]-N-methyl-carbamate A solution of Boc2O (7163.92 mg, 32.82 mmol) was added dropwise to a stirred solution of 1-(3- bromo-4-pyridyl)-N-methyl-methanamine (CAS RN: 463941-58-4; 6.0 g, 29.84 mmol) in DCM (30 mL), at 25 °C. The mixture was stirred for 18 h at 23 °C before being evaporated, to give the title compound (9.0 g, 96% yield) as a light yellow oil. MS (ESI): m / z = 301.0 / 303.0 [M+H]+Step b): N-[[3-(3-chloroanilino)-4-pyridyl]methyl]-N-methyl-carbamic acid tert-butyl ester A solution of 3-chloroaniline (58.76 µL, 557.31 µmol), N-[(3-bromo-4-pyridyl)methyl]-N- methyl-carbamic acid tert-butyl ester (111.9 mg, 371.54 µmol) and cesium carbonate (302.64 mg, 928.85 µmol) in toluene (1.17 mL) was degassed under Nitrogen, before being treated with palladium diacetate (8.34 mg, 37.15 µmol) and racemic-2,2'-bis(diphenylphosphino)-1,1'- binaphthyl (46.27 mg, 74.31 µmol). The mixture was stirred at 100 °C for 16 h, before being poured into 2-methyl-THF and washed with water and brine. The organic layer was dried over Na2SO4, filtered, and evaporated. Purification by FC (SiO2; heptane / EtOAc) gave the title compound (65.7 mg, 50.84% yield) as a light brown oil. MS(ESI): m / z = 348.3 [M+H]+Step c): [3-(3-chloroanilino)-4-pyridyl]methyl-methyl-amine A solution of N-[[3-(3-chloroanilino)-4-pyridyl]methyl]-N-methyl-carbamic acid tert-butyl ester (175.6 mg, 504.83 µmol) in 4 M HCl in 1,4-dioxane (2.52 mL, 10.1 mmol) was stirred for 18 h at 23 °C, before being diluted with DCM, filtered over celite, and evaporated. Purification by FC (SiO2; DCM / MeOH) gave the title compound (83.9 mg, 60.38% yield) as a light brown oil. MS (ESI): m / z = 248.1 [M+H]+Example 48 3-[(3S)-4,4-difluoro-3-methyl-tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea or 3-[(3R)-4,4-difluoro-3-methyl-tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea To a solution of 4,4-difluoro-3-methyl-tetrahydrofuran-3-carboxylic acid (CAS RN: 1782346-79- 5; 100.0 mg, 0.6 mmol) and triethylamine (0.13 mL, 0.9 mmol) in 1,4-dioxane (1.25 mL) was added diphenylphosphoryl azide (182.23 mg, 0.66 mmol), at 23 °C. The mixture was stirred for 1 h at 60 °C and for 2 h at 80 °C, before being cooled down and treated with (1S)-N-methyl-1-(4- pyridyl)ethanamine (CAS RN: 42732-16-1; 81.99 mg). The mixture was stirred for 1 h at 23 °C, before being purified by RP-HPLC. Chiral SFC (Column Chiralpak IG, 250x20 mm, 5 µm, hexane / IPA / MeOH 70:15:15, 14 mL / min) gave the title compound (36.5 mg, 20.26% yield, tR = 16.17 min) as a yellow oil. MS (ESI): m / z = 300.0 [M+H]+Example 49 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-2-phenoxy-1-(4-pyridyl)ethyl]urea or 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-2-phenoxy-1-(4- pyridyl)ethyl]urea or 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-2-phenoxy-1- (4-pyridyl)ethyl]urea or 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-2- phenoxy-1-(4-pyridyl)ethyl]urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 174.78 mg, 1.1 mmol) in DCM (5.5 mL) was added DIPEA (1.25 mL, 7.3 mmol) followed by CDT (233.03 mg, 1.42 mmol). The mixture was stirred at 23 °C for 1 h, before being treated with N-methyl-2-phenoxy-1-(4-pyridyl)ethanamine (250 mg, 1.1 mmol) and stirred for 16 h at 23 °C. Purification by FC (SiO2; DCM / MeOH) gave 340 mg of the racemic mixture. Purification by chiral SFC (Column chiral Whelk(r,r), 5 µm, 250 x 20 mm, 25% MeOH) gave the title compound (46 mg, 11% yield, tR = 3.06 min) as a white powder. MS (ESI): m / z = 378.2 [M+H]+Step a): N-methyl-2-phenoxy-1-(4-pyridyl)ethanamine Titanium isopropoxide (2.1 mL, 7.09 mmol) was added at 0 °C over 2-5 min to a solution of 2- phenoxy-1-(4-pyridyl)ethanone (CAS RN: 1574141-85-7; 1440.0 mg, 6.75 mmol) in 2-propanol (9.65 mL). Then, methylamine ethanol (2.52 mL, 20.26 mmol) was added, and the mixture was allowed to warm up to 23 °C and stirred for another 18 h at this temperature, before being cooled down to 0 °C. Sodium borohydride (383.2 mg, 10.13 mmol) was added portionwise, and the mixture was stirred at 0 °C for 1 h before being diluted with EtOAc (2 mL) and brine (2 mL). The mixture was stirred for 10 min at 23 °C, before being filtered through celite. The organic layer was washed with brine, dried over Na2SO4, filtered, and evaporated. Purification by FC (SiO2; DCM / MeOH) gave the title compound (550 mg, 36% yield) as a yellow oil. MS (ESI): m / z = 229.2 [M+H]+ Example 50 1-methyl-3-[(1R,5R)-3-oxabicyclo[3.1.0]hexan-1-yl]-1-[(1S)-1-(4-pyridyl)ethyl]urea or 1- methyl-3-[(1S,5S)-3-oxabicyclo[3.1.0]hexan-1-yl]-1-[(1S)-1-(4-pyridyl)ethyl]urea To a solution of [3-oxabicyclo[3.1.0]hexan-1-yl]amine;hydrochloride (CAS RN: 2307776-44-7; 49.78 mg, 367.13 µmol) in DCM (734.27 µL) was added DIPEA (147.47 µL, 844.41 µmol) followed by CDT (90.38 mg, 550.7 µmol).The mixture was stirred at at 23 °C for 1 h before being treated with methyl-[(1S)-1-(4-pyridyl)ethyl]amine (CAS RN: 42732-16-1; 50 mg, 367.13 µmol). The mixture was stirred at 23°C for 16 h before being poured into 2-Me-THF and washed with water and brine. The combined organic layers were dried over Na2SO4 and evaporated. Purification by (Gemini NX, 12 nm, 5 μm, 100 x 30 mm, ACN / H2O + 0.1% TEA) gave the title compound as a mixture of diasteromers (55.3 mg, 55% yield) and as a white oil . MS (ESI): m / z = 262.3 [M+H]+ Starting from 40 mg of diasteromeric mixture, chiral SFC (Column chiral AD-H, 5 µm, 250 x 20 mm, 15 % MeOH) gave the title compound (9.3 mg, 23% yield, tR= 3.420 min) as a light yellow oil. MS (ESI): m / z = 262.2 [M+H]+Example 51 1-methyl-3-[(1R,5R)-3-oxabicyclo[3.1.0]hexan-1-yl]-1-[(1S)-1-(4-pyridyl)ethyl]urea or 1- methyl-3-[(1S,5S)-3-oxabicyclo[3.1.0]hexan-1-yl]-1-[(1S)-1-(4-pyridyl)ethyl]urea To a solution of [3-oxabicyclo[3.1.0]hexan-1-yl]amine;hydrochloride (CAS RN: 2307776-44-7; 49.78 mg, 367.13 µmol) in DCM (734.27 µL) was added DIPEA (147.47 µL, 844.41 µmol) followed by CDT (90.38 mg, 550.7 µmol).The mixture was stirred at at 23 °C for 1 h before being treated with methyl-[(1S)-1-(4-pyridyl)ethyl]amine (CAS RN: 42732-16-1; 50 mg, 367.13 µmol). The mixture was stirred at 23 °C for 16 h before being poured into 2-Me-THF and washed with water and brine. The combined organic layers were dried over Na2SO4and evaporated. Purification by (Gemini NX, 12 nm, 5 μm, 100 x 30 mm, ACN / H2O + 0.1% TEA) gave the title compound as a mixture of diasteromers (55.3 mg, 55% yield) and as a white oil. MS (ESI): m / z = 262.3 [M+H]+ Starting from 40 mg of diasteromeric mixture, chiral SFC (Column chiral AD-H, 5 µm, 250 x 20 mm, 15% MeOH) gave the title compound (10.1 mg, 25% yield, tR= 3.610 min) as a light yellow oil. MS (ESI): m / z = 262.2 [M+H]+Example 52 1-[[3-(difluoromethyl)-4-pyridyl]methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl- urea or 1-[[3-(difluoromethyl)-4-pyridyl]methyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 40 mg, 250.69 µmol) in DCM (600 µL) were added DIPEA (110 µL, 629.84 µmol) and CDT (60 mg, 329.03 µmol). The mixture wasgg stirred at 23 °C for 1 h. [3-(difluoromethyl)-4- pyridyl]methyl-methyl-amine (44 mg, 255.55 µmol) was added. The reaction mixture was stirred at 23 °C for 16 h. The combined organic layers were dried over Na2SO4and evaporated. Purification by (SiO2, DCM / MeOH) and SFC (chiral Whelk(r,r), 12 nm, 5 µm, 250 x 20 mm, 20% MeOH) gave the title compound (32.3 mg, 38% yield, tR = 1.853 min) as a light yellow viscous oil. MS (ESI): m / z = 322.1 [M+H]+Step a): [3-(difluoromethyl)-4-pyridyl]methanol A solution of 3-(difluoromethyl)isonicotinaldehyde (CAS RN: 1211541-96-6; 70 mg, 445.52 µmol) and methylamine hydrochloride (CAS RN: 593-51-1; 152 mg, 2.25 mmol) in MeOH (1.25 mL) was stirred at 23 °C for 1 h before being treated with sodium triacetoxyborohydride (290 mg, 1.37 mmol). The mixture was stirred at 23 °C for 2 h before being poured in MeOH, washed by NH4Cl and neutralized by NaOH The aqueous phase was extracted with EtOAc. The combined organic layers were dried over Na2SO4and evaporated. Purification by FC (SiO2, DCM / MeOH) gave the title compound (54 mg, 72% yield) as a colorless crystalline solid. MS (ESI): m / z = 160.1 [M+H]+Step b):[3-(difluoromethyl)-4-pyridyl]methyl-methyl-amine To a solution of [3-(difluoromethyl)-4-pyridyl]methanol (54 mg, 339.35 µmol) in dry THF was added DIPEA (209 µL, 713.96 µmol). The solution was cooled to to 0 °C before being treated with methanesulfonylchloride (66 µL, 853.02 µmol). The mixture was stirred at 0°C for 1 h before being treated with a 2.0 M solution of MeNH2 (850 µL, 1.7 mmol). The mixture was stirred at 23 °C for 4 h, after which additional 2.0 M solution of MeNH2(850 µL, 1.7 mmol) was added. The mixture was heated to 60 °C for 18 h before being poured onto EtOAc (20 mL) and washed with water and brine. The combined organic layers were dried over Na2SO4 and evaporated. Purification by FC (SiO2, DCM / MeOH) gave the title compound (44 mg, 72% yield) as a light yellow liquid. MS (ESI): m / z = 173.1 [M+H]+Example 53 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[1-(4-pyridyl)cyclobutyl]urea or 3-[(3R)- 4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[1-(4-pyridyl)cyclobutyl]urea To a solution of 4,4-difluorotetrahydrofuran-3-amine;hydrochloride (CAS RN: 2408969-70-8; 165.22 mg, 1.04 mmol) in DMF (0.500 mL) were added DIPEA (0.45 mL, 2.59 mmol) and CDT (220.93 mg, 1.35 mmol). The mixture was stirred at 50 °C for 1 h before being treated with N- methyl-1-(4-pyridyl)cyclobutanamine (CAS RN: 1500790-86-2; 210.0 mg, 1.04 mmol). The mixture was then heated at 80 °C for 2 h and then at 23 °C 18 h. Purification by RP-HPLC gave 167 mg of the racemic mixture. Further separation by chiral HPLC (Column chiral IF, 5 µm, 250 x 21 mm, Hexane / IPA / MeOH) gave the title compound (61.8 mg, 19% yield, tR= 11.89 min) as a light brown oil. MS (ESI): m / z = 312.2 [M+H]+Example 54 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[[3-(1H-pyrazol-5-yl)-4-pyridyl]methyl]urea Under argon, to a solution of 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[[3-[2-(2- trimethylsilylethoxymethyl)pyrazol-3-yl]-4-pyridyl]methyl]urea and 3-(4,4- difluorotetrahydrofuran-3-yl)-1-methyl-1-[[3-[2-(2-trimethylsilylethoxymethyl)pyrazol-3-yl]-4- pyridyl]methyl]urea (14.76 mg, 29.04 µmol) in DCM (232.99 µL) was added TFA (11.19 µL, 145.21 µmol). The mixture was stirred at 23 °C for 1.5 h after which additional TFA (33.56 µL, 435.62 µmol) was added. The mixture was stirred at 23 °C for 3.5 h, after which additional TFA (11.19 µL, 145.21 µmol) was added. The mixture was stirred at 23 °C for 1 h, after which additional TFA (9.6 µL, 124.65 µmol) was added and the mixture stirred at 23 °C for 2 h, after which additional TFA (44.75 µL, 580.83 µmol) was added. The mixture was stirred at 23 °C for 3 h and then concentrated in vacuo. Purification by FC(SiO2, heptane / EtOAc / EtOH) gave the title compound as a racemic mixture (9.69 mg, 99% yield) and as a white solid. MS (ESI): m / z = 338.2 [M+H]+Step a): trimethyl-[2-[[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1- yl]methoxy]ethyl]silane and trimethyl-[3-[[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)pyrazol-1-yl]methoxy]ethyl]silane Under argon, to a solution of 1H-pyrazole-5-boronic acid pinacol ester (CAS RN: 844501-71-9; 300 mg, 1.55 mmol) in THF, extra dry (3 mL) was added NaH 60% in mineral oil (68.03 mg, 1.7 mmol) at 0 °C. The mixture was left stirring at 23 °C for 90 min before being treated with 2- (trimethylsilyl)ethoxymethyl chloride (329.06 µL, 1.86 mmol) at 0 °C. The mixture was stirred at 23 °C for 28 h before being quenched with water, extracted with EtOAc and washed with brine. The combined organic layers were dried over MgSO4 and evaporated to give the title compound as a mixture of two pyrazole regioisomers (766.45 mg, quant.) as a yellow oil. The crude was directly engaged in the next transformation. MS (ESI): m / z = 243.2 [M+H-(CH3)2C-C(CH3)2]+Step b): 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[[3-[2-(2- trimethylsilylethoxymethyl)pyrazol-3-yl]-4-pyridyl]methyl]urea and 3-(4,4- difluorotetrahydrofuran-3-yl)-1-methyl-1-[[3-[3-(2-trimethylsilylethoxymethyl)pyrazol-3-yl]-4- pyridyl]methyl]urea In a vial under argon, trimethyl-[2-[[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1- yl]methoxy]ethyl]silane (56.32 mg, 128.51 µmol), Cs2CO3(125.62 mg, 385.54 µmol), cataCXium Pd G4 (9.54 mg, 12.85 µmol) and 1-[(3-bromo-4-pyridyl)methyl]-3-(4,4-difluorotetrahydrofuran- 3-yl)-1-methyl-urea from Example 28 (50 mg, 128.51 µmol) were suspended in 1,4-dioxane (321 µL) and water (321 µL). The mixture was stirred at 100 °C for 3 h before being poured in EtOAc, filtered over celite and evaporated. Purification by FC (SiO2, heptane / EtOAc / EtOH) gave the title compound as a mixture of two pyrazole regioisomers (14.76 mg, 22% yield) and as a colorless oil. MS (ESI): m / z = 468.4 [M+H]+Example 55 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-2-hydroxy-1-(4-pyridyl)ethyl]-1-methyl-urea or 3-[(3R)-4,4-difluorotetrahydrofurapyrimidin-3-yl]-1-[(1R)-2-hydroxy-1-(4-pyridyl)ethyl]-1- methyl-urea or 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-2-hydroxy-1-(4- pyridyl)ethyl]-1-methyl-urea or 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-2-hydroxy-1- (4-pyridyl)ethyl]-1-methyl-urea To a solution of the diasteromeric mixture of 1-[2-[tert-butyl(dimethyl)silyl]oxy-1-(4- pyridyl)ethyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea (48.6 mg, 0.111 mmol) in DCM (250 µL) was added TFA (42.8 µL, 555.53 µmol). The reaction mixture was stirred at 23 °C over 1 h, before being evaporated. Purification by FC (SiO2, DCM / MeOH) gave the title compound as a diasteromeric mixture. Starting from the diasteromeric mixture, chiral SFC (Column chiral Amyl, 5 µm, 250 x 20 mm, 15 %MeOH) gave the title compound (3.4 mg, 9.55%, tR= 3.972 min) as a colorless oil. MS (ESI): m / z = 284.1 [M+H]+Step a): tert-butyl N-[2-hydroxy-1-(4-pyridyl)ethyl]carbamate To a solution of 2-amino-2-(4-pyridyl)ethanol (CAS RN: 100-43-6; 25.0 g, 180.94 mmol) in MeOH (700 mL) were added TEA (75.66 mL, 542.81 mmol) and Boc2O (39.49 g, 180.94 mmol). The mixture was stirred at 25 °C for 2 h. Purification by FC (PE / EtOAc) gave the title compound as a racemic mixture (22.3 g, 52% yield) and as a white solid. MS (ESI): m / z = 239.0 [M+H]+Step b): tert-butyl N-[2-[tert-butyl(dimethyl)silyl]oxy-1-(4-pyridyl)ethyl]carbamate To a solution of tert-butyl N-[2-hydroxy-1-(4-pyridyl)ethyl]carbamate (750.0 mg, 3.15 mmol) in DCM (20 mL) were added 1H-imidazole (535.38 mg, 7.87 mmol) and tert-butyl-chloro- dimethylsilane (1181.54 mg, 7.87 mmol). The mixture was stirred at 20 °C for 16 h. Purification by FC (PE / EtOAc) gave the title compound as a racemic mixture (1090.0 mg, 98% yield) and as white solid. MS (ESI): m / z = 353.1 [M+H]+Step c): tert-butyl N-[2-[tert-butyl(dimethyl)silyl]oxy-1-(4-pyridyl)ethyl]-N-methyl-carbamic acid tert-butyl ester To a solution of tert-butyl N-[2-[tert-butyl(dimethyl)silyl]oxy-1-(4-pyridyl)ethyl]carbamate (100 mg, 283.66 µmol) in DMF (3 mL) was added NaH 60% in mineral oil (13.62 mg, 567.31 µmol) at 0°C. The mixture was stirred at 0° C for 30 min before being treated with iodomethane (35.47 µL, 567.31 µmol). The mixture was stirred at 0 °C for 45min before being poured in EtOAc and washed with water and brine. The combined organic layers were dried over MgSO4and evaporated. Purification by FC (SiO2, heptane / EtOAc) gave the title compound as a racemic mixture (91 mg, 83% yield) and as a yellow liquid. MS (ESI): m / z = 367.3 [M+H]+Step d): [2-[tert-butyl(dimethyl)silyl]oxy-1-(4-pyridyl)ethyl]-methyl-amine. 1:1 2,2,2- trifluoroacetic acid To a solution of tert-butyl N-[2-[tert-butyl(dimethyl)silyl]oxy-1-(4-pyridyl)ethyl]-N-methyl- carbamic acid tert-butyl ester (91 mg, 0.236 mmol) in DCM (1.2 mL) was added TFA (134.45 mg, 90.84 µL, 1.18 mmol). The mixture was stirred at 23 °C over 1.8 h, then concentrated under vacuo to give the title compound as a racemic mixture (123.9 mg, 97%, 70% purity) and as a light yellow liquid which was directly used to the next step without further purification. MS (ESI): m / z = 267.3 [M+H]+Step e): 1-[2-[tert-butyl(dimethyl)silyl]oxy-1-(4-pyridyl)ethyl]-3-(4,4-difluorotetrahydrofuran-3- yl)-1-methyl-urea To a solution of 4,4-difluorotetrahydrofuran-3-amine;hydrochloride (CAS RN: 2408969-70-8; 60.54 mg, 384.16 µmol) in DCM (1 mL) were added DIPEA (268.37 µL, 1.54 mmol) and CDT (75.66 mg, 460.99 µmol). The mixture was stirred at 23 °C for 1 h before being treated with [2- [tert-butyl(dimethyl)silyl]oxy-1-(4-pyridyl)ethyl]-methyl-amine 1:1 TFA (208.8 mg, 384.16 µmol) in DCM (1 mL) and DMF (100 µL). The mixture was stirred at 23 °C over 17 h, before being evaporated. Purification by FC (SiO2, DCM / MeOH) gave the title compound as a diasteromeric mixture (48.6 mg, 29% yield) and as a light yellow oil. MS (ESI): m / z = 416.3 [M+H]+Example 56 3-[3-(difluoromethyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea To a solution of [3-(difluoromethyl)tetrahydrofuran-3-yl]amine;hydrochloride (CAS RN: 2742653-30-9; 76.48 mg, 440.56 µmol) in DMF (2.2 mL) were added DIPEA (307.77 µL, 1.76 mmol) and CDT (79.54 mg, 484.62 µmol). The mixture was stirred at 75 °C for 1h before being treated with methyl-[(1S)-1-(4-pyridyl)ethyl]amine (CAS RN: 42732-16-1; 60 mg, 440.56 µmol). The mixture was stirred at 75 °C for 16 h. Purification by RP-HPLC gave the title compound as a diasteromeric mixture (73.2 mg, 53% yield) and as a colorless gum. MS (ESI): m / z = 298.2 [M- H]˗Example 57 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(3-phenyl-4-pyridyl)methyl]urea or 3- [(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(3-phenyl-4-pyridyl)methyl]urea In a vial under argon, benzeneboronic acid, pinacol ester (34.2 mg, 162.78 µmol), Cs2CO3(159.11 mg, 488.35 µmol), cataCXium Pd G4 (12.08 mg, 16.27 µmol) and 1-[(3-bromo-4-pyridyl)methyl]- 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea from Example 28 (60 mg, 162.78 µmol) were suspended in 1,4-dioxane (405 µL) and water (405 µL). The mixture was stirred at 100 °C for 4 h before being poured in EtOAc, filtered over celite and concentrated in vacuo. Purification by FC (SiO2, heptane / EtOAc / EtOH) gave the title compound as a racemic mixture (45.13 mg, 80% yield) and as an off-white oil. MS (ESI): m / z = 348.2 [M+H]+Starting from 45.13 mg of diasteromeric mixture, chiral SFC (Column chiral OZ, 5 µm, 250 x 20 mm, 20 % MeOH) gave the title compound (24.29 mg, 54% yield, tR= 1.953 min) as a white solid. MS (ESI): m / z = 348.2 [M+H]+Example 58 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]thiourea To a solution of 4,4-difluorotetrahydrofuran-3-amine;hydrochloride (CAS RN: 2408969-70-8; 117.16 mg, 734.27 µmol) in DCM, extra dry (2.38 mL) were added DIPEA (384.72 µL, 2.2 mmol) and 1,1'-thiocarbonyldiimidazole (143.94 mg, 807.7 µmol). The mixture was stirred at 23 °C for 30 min before being treated with methyl-[(1S)-1-(4-pyridyl)ethyl]amine (CAS RN: 42732-16-1; 100 mg, 734.27 µmol). The mixture was stirred at 23 °C for 16 h before being poured in MeOH and evaporated. Purification by FC (SiO2, DCM / MeOH) gave the title compound as a diasteromeric mixture (25.1 mg, 10.89% yield) and as a light yellow oil. MS (ESI): m / z = 302.2 [M+H]+Example 59 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[[3-(3-methyl-1H-pyrazol-5-yl)-4- pyridyl]methyl]urea Under argon, to a solution of 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[[3-[5-methyl-2- (2-trimethylsilylethoxymethyl)pyrazol-3-yl]-4-pyridyl]methyl]urea and 3-(4,4- difluorotetrahydrofuran-3-yl)-1-methyl-1-[[3-[5-methyl-1-(2- trimethylsilylethoxymethyl)pyrazol-3-yl]-4-pyridyl]methyl]urea (41.87 mg, 0.080 mmol in DCM, extra dry (400 µL) was added TFA (123.24 µL, 1.6 mmol). The mixture was stirred at 23 °C for 4 h after which additional TFA (61.62 µL, 789.83 µmol) was added. The mixture was stirred at 23 °C for 1.5 h after which the mixture was concentrated in vacuo. Purification by FC (SiO2, heptane / EtOAc / EtOH) gave the title compound as a racemic mixture (27.68 mg, 98% yield) and as a white solid. MS (ESI): m / z = 352.2 [M+H]+Step a): trimethyl-[2-[[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1- yl]methoxy]ethyl]silane and trimethyl-[2-[[5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2-yl)pyrazol-1-yl]methoxy]ethyl]silane Under argon, to a solution of 1H-pyrazole-5-boronic acid pinacol ester (CAS RN: 1888441-67-5; 300 mg, 1.44 mmol) in THF, extra dry (2.5 mL) was added NaH 60% in mineral oil (63.44 mg, 1.586 mmol) at 0 °C. The mixture was left stirring at 23 °C for 90 min before being treated with 2-(trimethylsilyl)ethoxymethyl chloride (306.87 µL, 1.73 mmol) at 0 °C. The mixture was stirred at 23 °C for 28 h before being quenched with water, extracted with EtOAc and washed with brine. The combined organic layers were dried over MgSO4 and evaporated to give the title compound as a mixture of two pyrazole regioisomers (437.06 mg, 79% yield) as a colorless oil. The crude was directly engaged in the next transformation. MS (ESI): m / z = 256.4 [M+H-(CH3)2C-C(CH3)2]+Step b): 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[[3-[5-methyl-2-(2- trimethylsilylethoxymethyl)pyrazol-3-yl]-4-pyridyl]methyl]urea and 3-(4,4- difluorotetrahydrofuran-3-yl)-1-methyl-1-[[3-[5-methyl-1-(2-trimethylsilylethoxymethyl)pyrazol- 3-yl]-4-pyridyl]methyl]urea In a vial under argon, trimethyl-[2-[[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)pyrazol-1-yl]methoxy]ethyl]silane and trimethyl-[2-[[5-methyl-3-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)pyrazol-1-yl]methoxy]ethyl]silane as the two pyrazole regioisomers (100 mg, 260.1 µmol), Cs2CO3 (254.24 mg, 780.3 µmol), cataCXium Pd G4 (19.3 mg, 26.01 µmol) and 1- [(3-bromo-4-pyridyl)methyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea from Example 28 (95.87 mg, 260.1 µmol) were suspended in 1,4-dioxane (650.25 µL) and water (650.25 µL). The mixture was stirred at 100 °C for 3 h before being poured in EtOAc, filtered over celite and concentrated in vacuo. Purification by FC (SiO2, heptane / EtOAc / EtOH) gave the title compound as a mixture of two pyrazole regioisomers (41.87 mg, 31% yield) and as a colorless oil. MS (ESI): m / z = 482.3 [M+H]+Example 60 2-cyano-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]guanidine To a solution of 3-(4,4-difluorotetrahydrofuran-3-yl)-1,2-dimethyl-1-[(1S)-1-(4- pyridyl)ethyl]isothiourea (48 mg, 152.2 µmol) in THF, extra dry (500 µL) was added cyanamide (63.98 mg, 1.52 mmol) at 23 °C. The mixture was stirred at 23 °C for 16 h after which further DIPEA (53.16 µL, 304.39 µmol) was added. The reaction was heated to 45 °C for 32 h before being concentrated under reduced pressure. Purification by FC (SiO2, DCM / MeOH) followed by RP FC (MeCN / H2O) gave the title compound as a diasteromeric mixture (7.4 mg, 15% yield) and as a colorless oil. MS (ESI): m / z = 310.1 [M+H]+Step a): 3-(4,4-difluorotetrahydrofuran-3-yl)-1,2-dimethyl-1-[(1S)-1-(4-pyridyl)ethyl]isothiourea To a solution of Example 58: 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]thiourea (46.1 mg, 152.97 µmol) in MeOH, extra dry (1 mL) at -78 °C was added dropwise iodomethane (309 µL, 4.94 mmol). The mixture was stirred at 23 °C for 16 h. before being treated with 2 M NH3in MeOH and evaporated, to give the crude title compound (45 mg, 47% yield) as a light yellow oil which was directly used in the next step. MS (ESI): m / z = 316.1 [M+H]+Example 61 1-Methyl-3-(5-oxotetrahydrofuran-3-yl)-1-[(1S)-1-(4-pyridyl)ethyl]urea To a solution of 4-aminotetrahydrofuran-2-one;hydrochloride (CAS RN: 138846-59-0; 100 mg, 726.96 µmol) in DCM (5 mL) were added DIPEA (507.85 µL, 2.91 mmol) followed by CDT (143.17 mg, 872.35 µmol), at 23 °C. The reaction mixture was stirred at 23 °C for 1 h. Then, methyl-[(1S)-1-(4-pyridyl)ethyl]amine;dihydrochloride (CAS RN: 42732-16-1; 152.02 mg, 726.96 µmol) in DCM (5 mL) was added and the reaction mixture was stirred at 23 °C for 15 h. The solvent was evaporated. Purification by FC (SiO2; DCM / MeOH ) and by RP-HPLC (YMC- Triart C18, 12nm, 5μm, 100 x 30mm, CH3CN / H2O+0.1% TEA) delivered the title compound as a mixture of diasteromers (171.9 mg, 88% yield, tR = 0.825 min) and as a colorless oil. MS (ESI): m / z = 264.2 [M+H]+Example 62 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-[[(3S)-tetrahydrofuran-3-yl]methyl]- 4-pyridyl]methyl]urea or 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-[[(3R)- tetrahydrofuran-3-yl]methyl]-4-pyridyl]methyl]urea or 3-[(3R)-4,4-difluorotetrahydrofuran-3- yl]-1-methyl-1-[[3-[[(3S)-tetrahydrofuran-3-yl]methyl]-4-pyridyl]methyl]urea or 3-[(3R)-4,4- difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-[[(3R)-tetrahydrofuran-3-yl]methyl]-4- pyridyl]methyl]urea To a solution of 4,4-difluorotetrahydrofuran-3-amine;hydrochloride (CAS RN: 2408969-70-8; 171.45 mg, 1.07 mmol) in DCM (25 mL) were added DIPEA (0.75 mL, 4.3 mmol) followed by CDT (193.99 mg, 1.18 mmol). The reaction mixture was stirred at 23 °C for 2 h, before being treated with N-methyl-1-[3-(tetrahydrofuran-3-ylmethyl)-4- pyridyl]methanamine;dihydrochloride (300.0 mg, 1.07 mmol). The mixture was stirred at 23 °C for 20 h before being treated with water. The aqueous layer was back-extracted three times with DCM. The organic layers were dried over Na2SO4 and evaporated. Purification by RP-HPLC (XBridge BEH C18, 100 x 19mm, 5 µM, MeCN / H2O+0.1% HCl) and chiral SFC (Column Chiralpak IF, 250x20 mm, 5 µm, 25% / 25% IPA / MeOH) delivered the title compound (16.5 mg, 4% yield, tR= 21.23 min) as a yellow oil. MS (ESI): m / z = 356.2 [M+H]+Step a: tert-butyl N-[(3-bromo-4-pyridyl)methyl]-N-methyl-carbamate Boc2O (7.16 g, 32.82 mmol) was added dropwise to a solution of 1-(3-bromo-4-pyridyl)-N- methyl-methanamine (CAS RN: 73335-64-5; 6.0 g, 29.84 mmol) in DCM (30 mL) at 25 °C. After stirring for 18 h, the solvent was evaporated to give the title compound (9.0 g, 96% yield) as a light yellow oil. MS (ESI): m / z = 303.0 [M+H]+Step b: tert-butyl N-methyl-N-[[3-[(E)-tetrahydrofuran-3-ylidenemethyl]-4-pyridyl]methyl] carbamate In a vial under argon, 4,4,5,5-tetramethyl-2-[(Z)-tetrahydrofuran-3-ylidenemethyl]-1,3,2- dioxaborolane (CAS RN: 2365173-52-8; 800.0 mg, 3.81 mmol), tert-butyl N-[(3-bromo-4- pyridyl)methyl]-N-methyl-carbamate (1.147 g, 3.81 mmol), K2CO3 (1.053 g, 7.62 mmol) and (PPh3)2PdCl2·DCM complex (466.11 mg, 0.57 mmol) were suspended in 1,4-dioxane (32 mL) and water (8 mL). The mixture was sparged with Argon for 10 min and then stirred vigorously at 90 °C for 16 h. After cooling to 23 °C, the mixture was diluted with EtOAc, filtered and evaporated. Purification by FC (SiO2; PE / THF) delivered the title compound (760 mg, 60% yield) as a light brown solid. MS (ESI): m / z = 305.2 [M-Bu+H]+Step c: tert-butyl N-methyl-N-[[3-(tetrahydrofuran-3-ylmethyl)-4-pyridyl]methyl]carbamate tert-Butyl N-methyl-N-[[3-[(E)-tetrahydrofuran-3-ylidenemethyl]-4-pyridyl]methyl]carbamate (100.0 mg, 0.33 mmol) was dissolved in EtOAc (15 mL) and hydrogenated at 3800 mmHg over Pd / C 10% (14.14 mg, 0.01 mmol) for 48 h. The reaction mixture was filtered to remove Pd / C and the solvent evaporated to deliver the title compound (100.0 mg, 93% yield) as a light yellow oil. MS (ESI): m / z = 307.2 [M+H]+Step d: N-methyl-1-[3-(tetrahydrofuran-3-ylmethyl)-4-pyridyl]methanamine;dihydrochloride tert-Butyl N-methyl-N-[[3-(tetrahydrofuran-3-ylmethyl)-4-pyridyl]methyl]carbamate (600.0 mg, 1.96 mmol) was dissolved in MeOH (25 mL) and HCl (4 N in 1,4-dioxane) (0.49 mL, 1.96 mmol) was added. The reaction was stirred at 25 °C for 16 h. The solvent was evaporated and the residue triturated with Et2O, filtered and dried to deliver the title compound (350.0 mg, 61% yield) as a yellow solid. MS (ESI): m / z = 207.2 [M+H]+ Synthesis of the most common intermediate 1-[(3-bromo-4-pyridyl)methyl]-3-[(3S)-4,4- difluorotetrahydrofuran-3-yl]-1-methyl-urea Int-1 for Examples 63, 64, 65, 66, 67, 70 and 74 To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 474.78 mg, 2.98 mmol) in DCM (7 mL) were added DIPEA (1.56 mL, 8.93 mmol) followed by CDT (732.54 mg, 4.46 mmol). The mixture was stirred at 23 °C for 2 h. Then, 1-(3-bromopyridin- 4-yl)-n-methylmethanamine (CAS RN: 463941-58-4; 418.08 µL, 2.98 mmol) was added. The reaction mixture was stirred at 23 °C for 20 h before being treated with water. The aqueous layer was back-extracted three times with DCM. The organic layers were dried over Na2SO4and evaporated. Purification by FC (SiO2; EtOAc / EtOH / Heptane) and by chiral SFC (Column Chiralpak IF, 250x20 mm, 5 µm, 26% MeOH) delivered the title compound (383.43 mg, 49% yield, tR = 1.512 min) as an off-white semisolid. MS (ESI): m / z = 352.0 [M+H]+Example 63 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-(4-pyridyl)-4-pyridyl]methyl]urea In a vial under argon, 1-[(3-bromo-4-pyridyl)methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]- 1-methyl-urea Int-1 (63.91 mg, 182.5 µmol), pyridine-4-boronic acid, pinacol ester (CAS RN: 181219-01-2; 41.17 mg, 200.75 µmol), Cs2CO3 (178.39 mg, 547.51 µmol) and cataCXium Pd G4 (13.55 mg, 18.25 µmol) were suspended in 1,4-dioxane (456.26 µL) and water (456.26 µL). The reaction mixture was sparged with Argon for 10 min and then stirred vigorously at 100 °C for 3 h. After cooling to 23 °C, the mixture was diluted with EtOAc, filtered and evaporated. Purification by FC (SiO2; EtOAc / EtOH / Heptane) delivered the title compound (39.78 mg, 61% yield) as a white solid. MS (ESI): m / z = 349.2 [M+H]+ Example 64 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-(3-pyridyl)-4-pyridyl]methyl]urea In a vial under argon, 1-[(3-bromo-4-pyridyl)methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]- 1-methyl-urea Int-1 (63.91 mg, 182.5 µmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)pyridine (CAS RN: 329214-79-1; 41.17 mg, 200.75 µmol), Cs2CO3 (178.39 mg, 547.51 µmol) and cataCXium Pd G4 (13.55 mg, 18.25 µmol) were suspended in 1,4-dioxane (456.26 µL) and water (456.26 µL). The mixture was sparged with Argon for 10 min and then stirred vigorously at 100 °C for 3 h. After cooling to 23 °C, the mixture was diluted with EtOAc, filtered and evaporated. Purification by FC (SiO2; EtOAc / EtOH / Heptane) delivered the title compound (43.08 mg, 68% yield) as a white solid. MS (ESI): m / z 349.2 [M+H]+Example 65 1-[[3-(4-chlorophenyl)-4-pyridyl]methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl- urea In a vial under argon, 1-[(3-bromo-4-pyridyl)methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]- 1-methyl-urea Int-1 (63.91 mg, 182.5 µmol), 4-chlorophenylboronic acid (CAS RN: 1679-18-1; 31.39 mg, 200.75 µmol), Cs2CO3 (178.39 mg, 547.51 µmol) and cataCXium Pd G4 (13.55 mg, 18.25 µmol) were suspended in 1,4-dioxane (456.26 µL) and water (456.26 µL). The reaction mixture was sparged with Argon for 10 min and then stirred vigorously at 100 °C for 3 h. After cooling to 23 °C, the mixture was diluted with EtOAc, filtered and evaporated. Purification by RP (C18, MeCN / H2O) delivered the title compound (19.31 mg, 28% yield) as a white solid. MS (ESI): m / z = 382.1 [M+H]+ Example 66 1-[[3-(2-chlorophenyl)-4-pyridyl]methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl- urea In a vial under argon, 1-[(3-bromo-4-pyridyl)methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]- 1-methyl-urea Int-1 (63.91 mg, 182.5 µmol), 2-chlorophenylboronic acid (CAS RN: 3900-89-8; 41.17 mg, 200.75 µmol), Cs2CO3(178.39 mg, 547.51 µmol) and cataCXium Pd G4 (13.55 mg, 18.25 µmol) were suspended in 1,4-dioxane (456.26 µL) and water (456.26 µL). The mixture was sparged with Argon for 10 min and then stirred vigorously at 100 °C for 3 h. After cooling to 23 °C, the mixture was diluted with EtOAc, filtered and evaporated. Purification by FC (SiO2; EtOAc / EtOH / Heptane) delivered the title compound (46.94 mg, 67% yield) as a white solid. MS (ESI): m / z 382.1 [M+H]+Example 67 1-[[3-(3-chlorophenyl)-4-pyridyl]methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl- urea In a vial under Argon, 1-[(3-bromo-4-pyridyl)methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]- 1-methyl-urea Int-1 (63.91 mg, 182.5 µmol), 3-chlorophenylboronic acid (CAS RN: 63503-60-6; 31.39 mg, 200.75 µmol), Cs2CO3 (178.39 mg, 547.51 µmol) and cataCXium Pd G4 (13.55 mg, 18.25 µmol) were suspended in 1,4-dioxane (456.26 µL) and water (456.26 µL). The reaction mixture was sparged with Argon for 10 min and then stirred vigorously at 100 °C for 3 h. After cooling to 23 °C, the mixture was diluted with EtOAc, filtered and evaporated. Purification by RP (C18, MeCN / H2O) delivered the title compound (30.25 mg, 43% yield) as a white solid. MS (ESI): m / z = 382.1 [M+H]+Example 68 1-[2-(3-chlorophenoxy)-1-(4-pyridyl)ethyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 26.67 mg, 167.15 µmol) in DCM (840 µL) were added DIPEA (190.75 µL, 1.11 mmol) followed by CDT (35.56 mg, 216.7 µmol). The mixture was stirred at 23 °C for for 2 h. Then, [2-(3- chlorophenoxy)-1-(4-pyridyl)ethyl]-methyl-amine;hydrochloride (50 mg, 167.11 µmol) was added. The reaction mixture was stirred at 23 °C for 16 h. The organic layers were dried over Na2SO4 and evaporated. Purification by RP-HPLC (Phenomenex Gemini NX C18, 12nm, 5μm, 100 x 30mm, CH3CN / H2O+0.1% HCOOH) delivered the title compound as a diasteromeric mixture (13 mg, 19% yield) and as an off-white semisolid. MS (ESI): m / z = 412.2 [M+H]+Step a: 2-(3-chlorophenoxy)-1-(4-pyridyl)ethanone To a solution of 3-chlorophenol (CAS RN: 108-43-0; 22.65 g, 176.19 mmol) in MeCN (150 mL) was added K2CO3(24.35 g, 176.19 mmol) at 25 °C.4-(Bromoacetyl)pyridine hydrobromide (CAS RN: 5349-17-7; 3.0 g, 10.68 mmol) was then added and the reaction stirred for 0.15 h at 60 °C. A second portion of 4-(bromoacetyl)pyridine hydrobromide (CAS RN: 5349-17-7; 5.0 g, 17.8 mmol) was then added and the reaction stirred for further 0.15 h at 60 °C. A third portion of 4- (bromoacetyl)pyridine hydrobromide (CAS RN: 5349-17-7; 8.0 g, 28.48 mmol) was then added and the reaction stirred for further 30 min at 60 °C. The solvent was evaporated. Purification by FC (SiO2; PE / EtOAc) delivered the title compound (10.76 g, 74%, yield) as a pink solid. MS (ESI): m / z = 248.0 [M+H]+Step b: 2-(3-chlorophenoxy)-N-methyl-1-(4-pyridyl)ethanamine;dihydrochloride A mixture of 2-(3-chlorophenoxy)-1-(4-pyridyl)ethanone (2.0 g, 8.07 mmol), MeNH2·HCl (CAS RN: 593-51-1; 1.09 g, 16.15 mmol), NaOAc (1.373 g, 20.19 mmol) in DCE (20 mL) was stirred at 70 °C for 2 h. To the reaction was added NaBH3CN (1.526 g, 24.22 mmol) and the resulting mixture was stirred at 25 °C for 12 h. The precipitate was filtered off and the filtrate evaporated. Purification by RP-HPLC (Phenomenex Luna C18, 15μm, 150 x 40mm, CH3CN / H2O+0.1% HCO2H) and titration with HCl delivered the title compound (253.11 mg, 12% yield) as a yellow solid. MS (ESI): m / z = 263.1 [M-2HCl+H]+Example 69 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[(3-prop-1-ynyl-4-pyridyl)methyl]urea In a vial under argon, bis(triphenylphosphine)palladium (II) chloride (3.06 mg, 4.36 µmol),TEA (91.21 µL, 654.39 µmol) and 1-[(3-bromo-4-pyridyl)methyl]-3-(4,4-difluorotetrahydrofuran-3- yl)-1-methyl-urea (80.4 mg, 0.218 mmol) were dissolved in THF extra dry (1.09 mL).1 M Prop- 1-yne solution (261.75 µL, 261.75 µmol) and CuI (1.66 mg, 8.73 µmol) were then added and the mixture heated to 65 °C. After 1.5 h, further 1 M prop-1-yne solution (218.13 µL, 218.13 µmol) was added and the mixture heated to 65 °C. After 4.5 h, further 1 M prop-1-yne solution (436.26 µL, 436.26 µmol) was added and the mixture heated to 65 °C. After 25 h, further 1 M prop-1-yne solution (436.26 µL, 436.26 µmol) was added. After 26 h, further bis(triphenylphosphine)palladium (II) chloride (15.31 mg, 21.81 µmol), CuI (8.31 mg, 43.63 µmol), TEA (91.21 µL, 654.39 µmol ) and 1 M prop-1-yne solution (436.26 µL, 436.26 µmol) were added. The reaction mixture was filtered through a celite pad and washed with EtOAc. The combined filtrate was evaporated. Purification by RP-HPLC (Phenomenex Gemini NX C18, 12nm, 5μm, 100 x 30mm, CH3CN / H2O+0.1% HCOOH) delivered the title compound (1.1 mg, 2% yield) as a light yellow oil. MS (ESI): m / z = 310.1 [M+H]+Step a: 1-[(3-bromo-4-pyridyl)methyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 39.68 mg, 248.68 µmol) in DCM (800 µL) were added DIPEA (130 µL, 746.05 µmol) followed by CDT (44.9 mg, 273.55 µmol). The reaction mixture was stirred at 23 °C for 16 h. Then, 1-(3- bromopyridin-4-yl)-n-methylmethanamine (CAS RN: 463941-58-4; 50 mg, 248.68 µmol) was added. The reaction mixture was stirred at 23 °C for 4 h. MeOH and Isolute were added. The organic layers were dried over Na2SO4 and evaporated. Purification by FC (SiO2; DCM / MeOH) delivered the title compound (80.4 mg, 88% yield) as a colorless oil. Example 70 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-(2-pyridyl)-4-pyridyl]methyl]urea In a vial under Argon, 1-[(3-bromo-4-pyridyl)methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]- 1-methyl-urea Int-1 (30.47 mg, 87.02 µmol), 2-tri-n-butylstannylpyridine (CAS RN: 17997-47-6; 69.64 µL, 174.03 µmol) and LiCl (7.38 mg, 174.03 µmol) and tetrakis(triphenylphosphine)palladium (20.11 mg, 17.4 µmol) were suspended in 1,4-dioxane (1.5 mL). The mixture was sparged with Argon for 10 min and then stirred vigorously at 100 °C for 15 h. After cooling to 23 °C, the mixture was diluted with EtOAc, filtered and evaporated. Purification by RP (C18, MeCN:H2O) and FC (SiO2; EtOAc / EtOH / Heptane) delivered the title compound (5.79 mg, 19% yield) as a white solid. MS (ESI): m / z = 349.1 [M+H]+Example 71 1-[2-(4-chlorophenoxy)-1-(4-pyridyl)ethyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 30.37 mg, 190.35 µmol) in DCM (956 µL) were added DIPEA (217.23 µL, 1.27 mmol) followed by CDT (40.5 mg, 246.75 µmol). The reaction mixture was stirred at 23 °C for 1 h. Then, [2-(4- chlorophenoxy)-1-(4-pyridyl)ethyl]-methyl-amine (50 mg, 190.31 µmol) was added. The reaction mixture was stirred at 23 °C for 16 h. The organic layers were dried over Na2SO4and evaporated. Purification by RP-HPLC (Phenomenex Gemini NX C18, 12nm, 5μm, 100 x 30mm, CH3CN / H2O+0.1% HCOOH) delivered the title compound as a diasteromeric mixture (23 mg, 29% yield) and as a white powder. MS (ESI): m / z = 412.1 [M+H]+Step a: 2-(4-chlorophenoxy)-1-(4-pyridyl)ethanone To a solution of 4-chlorophenol (CAS RN: 106-48-9; 2.75 g, 21.36 mmol) in MeCN (10 mL) was added K2CO3(6.18 g, 44.5 mmol) at 25 °C. 4-(bromoacetyl)pyridine hydrobromide (CAS RN: 5349-17-7; 5.0 g, 17.8 mmol) was then added and the reaction stirred at 25 °C for 12 h. The solvent was evaporated. Purification by RP-HPLC (CH3CN / H2O+0.1% NH3.H2O) delivered the title compound (3.0 g, 68% yield) as a white solid. MS (ESI): m / z = 248.6 [M+H]+Step b: 2-(4-chlorophenoxy)-N-methyl-1-(4-pyridyl)ethanamine A mixture of 2-(4-chlorophenoxy)-1-(4-pyridyl)ethanone (3.0 g, 12.11 mmol), MeNH2.HCl (CAS RN: 593-51-1; 1.7 g, 24.22 mmol), NaOAc (2.06 g, 30.28 mmol) in DCE (20 mL) was stirred at 70°C for 2 h. To the reaction was added NaBH3CN (2.29 g, 36.34 mmol) and the resulting mixture was stirred at 25 °C for 12 h. The precipitate was filtered off and the filtrate was evaporated. Purification by RP-HPLC (CH3CN / H2O+0.1% TEA) and trituration with HCl delivered the title compound (590.66 mg, 18% yield) as a yellow solid. MS (ESI): m / z = 263.2 [M+H]+Example 72 3-[(3S,4R)-4-hydroxytetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea or 3- [(3R,4S)-4-hydroxytetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea To a solution of (trans-4-amino-tetrahydrofuran-3-ol (CAS RN: 330975-13-8; 57.55 mg, 558.04 µmol) in DMF (1.12 mL) were added DIPEA (382.11 µL, 2.23 mmol) and TMSCl (72.78 µL, 558.04 µmol). The reaction was stirred at 23 °C for 30 min, before being treated with CDT (137.38 mg, 837.07 µmol). The reaction mixture was stirred at 75 °C for 40 min. Then, methyl-[(1S)-1-(4- pyridyl)ethyl]amine (CAS RN: 42732-16-1; 80 mg, 558.04 µmol) was added. The mixture was stirred at 75 °C for 16 h. The organic layers were dried over Na2SO4and evaporated. Purification by RP (C18, CH3CN / H2O) and chiral SFC (Column chiral Amy1, 5 µm, 250x20 mm, 28% MeOH) gave the title compound (8.7 mg, 6% yield, tR = 3.695 min) as a light brown solid. MS (ESI): m / z = 266.2 [M+H]+Example 73 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-(tetrahydropyran-4-ylmethyl)-4- pyridyl]methyl]urea or 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3- (tetrahydropyran-4-ylmethyl)-4-pyridyl]methyl]urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 166.3 mg, 1.04 mmol) in DCM (5 mL) were added DIPEA (910 µL, 5.21 mmol) followed by CDT (205.2 mg, 1.25 mmol). The reaction mixture was stirred at 23 °C for 40 min. Then, methyl-[[3- (tetrahydropyran-4-ylmethyl)-4-pyridyl]methyl]amine.2,2,2-trifluoroacetic acid (1.16 g, 1.04 mmol) was added. The reaction mixture was stirred at 23 °C for 16 h. The organic layers were dried over Na2SO4, mixed with Isolute and evaporated. Purification by FC (SiO2; DCM / MeOH) and by chiral SFC (Chiral column OZ-H, 5μm, 250 x 20 mm, 25% MeOH) delivered the title compound (24.9 mg, 6% yield, tR = 1.780 min) as a yellow gum. MS (ESI): m / z = 370.2 [M+H]+Step a: N-[(3-bromo-4-pyridyl)methyl]-N-methyl-carbamic acid tert-butyl ester To a solution of (3-bromo-4-pyridyl)methyl-methyl-amine (CAS RN: 463941-58-4; 2500 mg, 12.43 mmol) in DCM (60 mL) was added DIPEA (8.69 mL, 49.74 mmol), followed by the addition of Boc2O (4.33 mL, 18.65 mmol), at 23 °C. The mixture was for 17 h at this temperature, before being treated with water and diluted with DCM. The aqueous layer was extracted twice with DCM. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and evaporated. Purification by FC (SiO2; heptane / EtOAc), to give the title compound (3078 mg, 80.55%) as an orange oil. MS (ESI): m / z = 301.1 [M+H]+ Step b: N-methyl-N-[[3-(tetrahydropyran-4-ylidenemethyl)-4-pyridyl]methyl]carbamic acid tert- butyl ester To a solution of N-[(3-bromo-4-pyridyl)methyl]-N-methyl-carbamic acid tert-butyl ester (500 mg, 1.63 mmol) and 4,4,5,5-tetramethyl-2-(tetrahydropyran-4-ylidenemethyl)-1,3,2-dioxaborolane (364.6 mg, 1.63 mmol) in 1,4-dioxane (15 mL) and water (1.5 mL) was added K2CO3(674.58 mg, 4.88 mmol) under Argon, followed by the addition of dichloro(1,1’- bis(diphenylphosphino)ferrocene)palladium (II) (120.68 mg, 162.69 μmol). The mixture was stirred for 15 h at 90 °C, before being cooled down to 23 °C, filtered, and evaporated. Purification by FC (SiO2; DCM / MeOH) gave the title compound (413.8 mg, 75.89%) as an orange oil. MS (ESI): m / z = 319.2 [M+H]+Step c: N-methyl-N-[[3-(tetrahydropyran-4-ylmethyl)-4-pyridyl]methyl]carbamic acid tert-butyl ester A solution of N-methyl-N-[[3-(tetrahydropyran-4-ylidenemethyl)-4-pyridyl]methyl]carbamic acid tert-butyl ester (515 mg, 1.54 mmol) in MeOH (8 mL) was purged with Argon, followed by addition of Pd / C (163.52 mg, 153.65 µmol). The system was then purged with H2. The reaction mixture was stirred for 3 h at 23 °C, before being filtered on a celite pad, washed with MeOH, and evaporated, giving the title compound (433.8 mg, 79.3%) as an orange oil. MS (ESI): m / z = 321.2 [M+H]+Step d: methyl-[[3-(tetrahydropyran-4-ylmethyl)-4-pyridyl]methyl]amine 1:1 2,2,2- trifluoroacetic acid To a solution of N-methyl-N-[[3-(tetrahydropyran-4-ylmethyl)-4-pyridyl]methyl]carbamic acid tert-butyl ester (433.8 mg, 1.22 mmol) in DCM (6 mL) was added TFA (938.68 µL, 12.18 mmol) at 23 °C. The mixture was stirred for 3 h at this temperature, before being treated with more TFA (469.34 µL, 6.09 mmol). The mixture was stirred for another 2 h at 23 °C before being eevaporated, giving the title compound (1.16 g, 85.52%) as a brown oil. MS (ES): m / z = 221.2 [M+H]+Example 74 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-[4-(trifluoromethyl)phenyl]-4- pyridyl]methyl]urea In a vial under Argon, 1-[(3-bromo-4-pyridyl)methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]- 1-methyl-urea Int-1 (60.0 mg, 171.35 µmol), 4-(trifluoromethyl)phenylboronic acid (CAS RN: 128796-39-4; 36.91 mg, 188.49 µmol), Cs2CO3 (167.49 mg, 514.05 µmol) and cataCXium Pd G4 (12.72 mg, 17.14 µmol) were suspended in 1,4-dioxane (400 µL) and water (400 µL). The mixture was sparged with Argon for 10 min and then stirred vigorously at 100 °C for 3 h. After cooling to 23 °C, the mixture was diluted with EtOAc, filtered and evaporated. Purification by FC (SiO2; EtOAc / EtOH / Heptane) delivered the title compound (48.57 mg, 68% yield) as a white solid. MS (ESI): m / z 416.0 [M+H]+Example 75 [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1-methyl- urea and 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1- methyl-urea] or [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1-methyl- urea and 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1- methyl-urea] or [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1-methyl- urea and 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1- methyl-urea] or [3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1-methyl- urea and 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1- methyl-urea] or [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1-methyl- urea and 3-[(3R)-4,4-difluorotetrahydrofuran-3 yl]-1-[(1R)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1- methyl-urea] or [3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1-methyl- urea and 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3,5-dimethyl-4-pyridyl)ethyl]-1- methyl-urea] To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 195 mg, 1.22 mmol) in DCM (2.5 mL) were added DIPEA (534 µL, 3.06 mmol) followed by CDT (251 mg, 1.53 mmol). The reaction mixture was stirred at 23 °C for for 2 h. Then, 1-(3,5-dimethyl- 4-pyridyl)ethyl-methyl-amine (167.3 mg, 1.02 mmol) was added. The reaction mixture was stirred at 23 °C for 17 h. The mixture was treated with H2O and extracted with EtOAc. The organic layers were dried over MgSO4, and evaporated. Purification by FC (SiO2; Heptane / EtOAc / EtOH) and by SFC (Chiral column OZ-H, 5μm, 250 x 20 mm, 25% MeOH + 0.2% DIPEA) delivered the title compound as a mixture of two configurational isomers (4.34 mg, 1.32% yield, tR = 0.981 min) and as an off-white solid. MS (ESI): m / z = 314.2 [M+H]+Step a: 1-(3,5-dimethyl-4-pyridyl)ethanol Under argon, to a solution of 3,5-dimethylpyridine-4-carbaldehyde (CAS RN: 201286-64-8; 150 mg, 1.11 mmol) in THF (8 mL) was added 3.4 M MeMgBr in 2-Me-THF (816.03 µL, 2.77 mmol) dropwise at -78 °C. The reaction mixture was slowly warmed up to 0 °C over 3.5 h. The reaction was quenched with sat. aq. NH4Cl solution. The aqueous phase was extracted with EtOAc. The organic layers were dried over Na2SO4and evaporated, to deliver the title compound (184.2 mg, over quant.) as a yellow solid. The crude was directly engaged in the next transformation without further purification. MS (ESI): m / z = 152.1 [M+H]+Step b: 4-(1-chloroethyl)-3,5-dimethyl-pyridine In a flask under Argon, to a solution of 1-(3,5-dimethyl-4-pyridyl)ethanol (184.2 mg, 1.16 mmol) in DCM, extra dry (5 mL) was added SOCl2 (253.4 µL, 3.47 mmol) at 0 °C. The reaction mixture was stirred at 23 °C for 20 h. The mixture was quenched with sat. aq. NaHCO3 and extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered, and evaporated to deliver the title compound (261.78 mg, over quant.) as a yellow oil. The crude was directly engaged in the next transformation without further purification. MS (ESI): m / z = 170.0 [M+H]+Step c: 1-(3,5-dimethyl-4-pyridyl)ethyl-methyl-amine In a flask under Argon, 4-(1-chloroethyl)-3,5-dimethyl-pyridine (261.78 mg, 1.48 mmol), 2 M MeNH2 in THF (888.8 µL, 1.78 mmol) and K2CO3 (409.47 mg, 2.96 mmol) were suspended in DMF (7 mL). The mixture was stirred at 100 °C for 14 h. The reaction was cooled to 50 °C. Additional 2 M MeNH2 in THF (2.96 mL, 5.93 mmol) and KI (12.3 mg, 74.07 µmol) were added and the mixture was stirred at 50 °C for 18 h. The mixture was treated with H2O and extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered, and evaporated to deliver the title compound (167.3 mg, 57% yield) as a brown oil. MS (ESI): m / z = 165.2 [M+H]+Example 76 1-[(1S)-1-(3-bromo-4-pyridyl)ethyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-urea or 1-[(1S)-1-(3-bromo-4-pyridyl)ethyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl- urea or 1-[(1R)-1-(3-bromo-4-pyridyl)ethyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea or 1-[(1R)-1-(3-bromo-4-pyridyl)ethyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]- 1-methyl-urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 277 mg, 1.74 mmol) in DCM (3.5 mL) were added DIPEA (758 µL, 4.34 mmol) followed by CDT (356 mg, 2.17 mmol). The reaction mixture was stirred at 23 °C for 2 h. Then, 1-(3-bromo-4- pyridyl)ethyl-methyl-amine (611 mg, 1.45 mmol) was added. The reaction mixture was stirred at 23 °C for 20 h. The mixture was treated with H2O and extracted with EtOAc. The organic layers were dried over MgSO4, and evaporated. Purification by FC (SiO2; Heptane / EtOAc / EtOH) and by chiral SFC (Chiral column Whelk01 r,r , 5μm, 250 x 20 mm, 20% MeOH) delivered the title compound (4.34 mg, 1.32% yield, tR= 2.181 min) and as an off-white solid. MS (ESI): m / z = 364.1 [M+H]+Step a: 1-(3-bromo-4-pyridyl)ethyl-methyl-amine 1-(3-Bromopyridin-4-yl)ethanone (CAS RN: 111043-06-2; 325.95 µL, 2.5 mmol), 2 M MeNH2 in THF (1.5 mL, 3.00 mmol) and Ti(OiPr)4(740.05 µL, 2.5 mmol) were dissolved in THF, extra dry (6 mL). The mixture was stirred at 23 °C for 20 h. NaBH4 (283.68 mg, 7.5 mmol) was added at 0 °C and the mixture was stirred at 23 °C for 4.5 h. The reaction was quenched with 12 mL 25 % aq. NH3sol. and the mixture stirred at 23 °C for 1 h. The mixture was filtered over celite and the solvent evaporated. The crude was partitioned between EtOAc and 1 M NaOH aqueous solution. The aqueous phase was extracted with EtOAc. The organic layers were dried over MgSO4 and evaporated, to give the title compound (610.48 mg, 58% yield) as a yellow oil. MS (ESI): m / z 215.0 [M+H]+Example 77 1-[(1R)-2-(4-chlorophenoxy)-1-(4-pyridyl)ethyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea or 1-[(1R)-2-(4-chlorophenoxy)-1-(4-pyridyl)ethyl]-3-[(3R)-4,4- difluorotetrahydrofuran-3-yl]-1-methyl-urea or 1-[(1S)-2-(4-chlorophenoxy)-1-(4- pyridyl)ethyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-urea or 1-[(1S)-2-(4- chlorophenoxy)-1-(4-pyridyl)ethyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 30.37 mg, 190.35 µmol) in DCM (956 µL) were added DIPEA (217 µL, 1.27 mmol) followed by CDT (40.5 mg, 247 µmol). The reaction mixture was stirred at 23 °C for 1 h. Then, [2-(4- chlorophenoxy)-1-(4-pyridyl)ethyl]-methyl-amine (50.0 mg, 190 µmol) was added. The reaction mixture was stirred at 23 °C for 16 h. The organic layers were dried over MgSO4, and evaporated. Purification by RP-HPLC (Phenomenex Gemini NX C18, 12nm, 5μm, 100 x 30mm, CH3CN / H2O+0.1% HCOOH) and by chiral SFC (Chiral column Wrr, 5μm, 250 x 20 mm, 24% MeOH+0.2% TEA) delivered the title compound (5.6 mg, 25% yield, tR= 3.069 min) and as a white powder. MS (ESI): m / z = 412.1 [M+H]+Step a: 2-(4-chlorophenoxy)-1-(4-pyridyl)ethanone To a solution of 4-chlorophenol (CAS RN: 106-48-9; 2.75 g, 21.36 mmol) in MeCN (10 mL) were added K2CO3(6.18 g, 44.49 mmol) and 4-(bromoacetyl)pyridine hydrobromide (CAS RN: 5349- 17-7; 5g, 17.8 mmol). The mixture was stirred at 25 °C for 12 h. The solvent was removed in vacuo. Purification by RP-HPLC (0.1% NH3.H2O) delivered the title compound (3.0 g, 68% yield) as a white solid. MS (ESI): m / z = 248.6 [M+H]+Step b: 2-(4-chlorophenoxy)-N-methyl-1-(4-pyridyl)ethanamine A mixture of 2-(4-chlorophenoxy)-1-(4-pyridyl)ethanone (3.0 g, 12.11 mmol), MeNH3 HCl (1.7 g, 24.22 mmol), NaOAc (2.06 g, 30.28 mmol) in DCE (20 mL) was stirred at 70 °C for 2 h. NaBH3CN (2.29 g, 36.34 mmol) was then added. The mixture was stirred at 25 °C for 1 h. The reaction was filtered and evaporated. Purification by RP-HPLC (0.1% NH3·H2O) delivered the title compound (590.66 mg, 19% yield) as a brown oil. MS (ESI): m / z = 263.2 [M+H]+Example 78 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-3-(4-fluorophenyl)-1-(4-pyridyl)propyl]-1- methyl-urea or 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-3-(4-fluorophenyl)-1-(4- pyridyl)propyl]-1-methyl-urea or 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-3-(4- fluorophenyl)-1-(4-pyridyl)propyl]-1-methyl-urea or 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]- 1-[(1R)-3-(4-fluorophenyl)-1-(4-pyridyl)propyl]-1-methyl-urea

[0002] To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 102 mg, 639.26 µmol) in DCM (2.3 mL) were added DIPEA (280 µL, 1.6 mmol) followed by CDT (152 mg, 926 µmol). The reaction mixture was stirred at 23 °C for 1 h. Then, [3-(4- fluorophenyl)-1-(4-pyridyl)propyl]-methyl-amine (150.0 mg, 614 µmol) was added. The reaction mixture was stirred at 23 °C for 16 h. The organic layers were dried over MgSO4, and evaporated. Purification by FC (SiO2; DCM / MeOH) and by chiral SFC (Chiral column Wrr, 5μm, 250 x 20 mm, 29% EtOH) delivered the title compound (25 mg, 14% yield, tR = 3.005min) as a white powder. MS (ESI): m / z = 394.2 [M+H]+Step a: N-[(E)-2-(4-fluorophenyl)ethylideneamino]-4-methyl-benzenesulfonamide To a solution of (4-fluorophenyl)acetaldehyde (CAS RN: 1736-67-0; 3.5 g, 25.34 mmol) in MeOH (100 mL) was added 4-methylbenzenesulfonhydrazide (CAS RN: 1576-35-8; 4.8 g, 25.34 mmol) and mixture was stirred at 60 °C for 0.4 h. The mixture was evaporated. Purification by FC (SiO2; PE / EtOAc) delivered the title compound (7.8 g, quant.) as a yellow oil. MS (ESI): m / z = 307.0 [M+H]+Step b: 3-(4-fluorophenyl)-1-(4-pyridyl)propan-1-one To a solution of 4-pyridinecarboxaldehyde (CAS RN: 872-85-5; 1.56 mL, 16.32 mmol) in 1,4- dioxane (100 mL) were added N-[(E)-2-(4-fluorophenyl)ethylideneamino]-4-methyl- benzenesulfonamide (5.0 g, 16.32 mmol) and Cs2CO3(1.6 g, 48.96 mmol). The mixture was stirred at 110 °C for 12 h. The mixture was evaporated. Purification by FC (SiO2; PE / EtOAc) delivered the title compound (2.8 g, 75% yield) as a yellow oil. MS (ESI): m / z = 230.1 [M+H]+Step c: 3-(4-fluorophenyl)-N-methyl-1-(4-pyridyl)propan-1-amine;dihydrochloride To a solution of 3-(4-fluorophenyl)-1-(4-pyridyl)propan-1-one (2.8 g, 12.2 mmol) in THF (100 mL) was added AcOH (70 µL, 1.22 mmol) and the reaction was stirred at 25 °C for 15 min. MeNH2 in THF (73.28 mL, 146.56 mmol) was then added and the resulting mixture stirred at 25 °C for 4 h. NaBH3CN (3.8 g, 61.07 mmol) was added portionwise at 0 °C and the mixture stirred at 25 °C for 12 h. The mixture was evaporated. Purification by RP-HPLC (C18, CH3CN / H2O ) delivered the title compound (983.7 mg, 25% yield) as a yellow solid. MS (ESI): m / z = 245.1 [M+H]+Example 79 1-[(1S)-3,3-difluoro-1-(4-pyridyl)propyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl- urea or 1-[(1S)-3,3-difluoro-1-(4-pyridyl)propyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea or 1-[(1R)-3,3-difluoro-1-(4-pyridyl)propyl]-3-[(3R)-4,4-difluorotetrahydrofuran- 3-yl]-1-methyl-urea or 1-[(1R)-3,3-difluoro-1-(4-pyridyl)propyl]-3-[(3S)-4,4- difluorotetrahydrofuran-3-yl]-1-methyl-urea To a 0 °C solution of 3,3-difluoro-N-methyl-1-(4-pyridyl)propan-1-amine; 2,2,2-trifluoroacetic acid (0.3 g, 0.72 mmol) in DCM (25 mL) were added TEA (710 µL, 5.07 mmol) followed by CDI (180 mg, 1.09 mmol). The reaction mixture was stirred at 25 °C for 1 h. Then, (4,4- difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 130.0 mg, 800 µmol) was added. The mixture was stirred at 23 °C for 18 h. The organic layers were dried over MgSO4, and evaporated. Purification by RP-HPLC (C18 Chromatorex SMB, CH3CN / H2O) and by chiral HPLC (Chiralpack IG, 5μm, 250 x 20 mm, Hexane / MeOH / IPA 50% / 25% / 25%) delivered the title compound (17.6 mg, 7% yield, tR= 15.46 min) as a yellow solid. MS (ESI): m / z = 336.0 [M+H]+Step a: methyl 4,4-difluoro-2-(4-pyridyl)butanoate To a solution of bis(isopropyl)amine (4.65 mL, 33.19 mmol) in THF (60 mL) was added n-BuLi 1 M in THF (14.34 mL, 35.84 mmol) dropwise, at 0 °C. The reaction was stirred at 0 °C for 30 min. Then, methyl 2-(pyridin-4-yl)acetate (CAS RN: 29800-89-3; 4.01 g, 26.55 mmol) in THF (60 mL) was added, at -40 °C. The mixture was stirred for 1 h at 0 °C. Afterwards, a solution of 2,2-difluoroethyl trifluoromethanesulfonate (3.87 mL, 29.2 mmol) in THF (40 ml) was added dropwise and the resulting mixture was stirred at -40 °C for 1 h. Then, the reaction was warmed to 23 °C and stirred for 18 h. The mixture was poured into NH4Cl sat. aq. sol. (100 mL) and extracted by EtOAc. The organic layers were dried over Na2SO4, and evaporated. Purification by FC (SiO2; PE / EtOAc) delivered the title compound (2.3 g, 38% yield). MS (ESI): m / z = 216.2 [M+H]+Step b: 4,4-difluoro-2-(4-pyridyl)butanehydrazide To solution of methyl 4,4-difluoro-2-(4-pyridyl)butanoate (2.3 g, 10.05 mmol) and hydrazine hydrate (CAS RN: 7803-57-8; 1.18 mL, 30.14 mmol) in EtOH (25 mL) was stirred at 75 °C for 18 h, before being evaporated. Purification by FC (SiO2; CH3CN / MeOH) delivered the title compound (1.18 g, 49% yield). MS (ESI): m / z = 216.2 [M+H]+Step c: tert-butyl N-[3,3-difluoro-1-(4-pyridyl)propyl]carbamate 4,4-Difluoro-2-(4-pyridyl)butanehydrazide (2.4 g, 11.15 mmol) was dissolved in HCl (64.0 mL, 182.6 mmol) and the solution was cooled to 0 °C. NaNO2(2.31 g, 33.46 mmol) in H2O (12 mL) was added dropwise over 40 min. The reaction was stirred at 0 °C for 1 h. Et2O (100 mL) was added and the mixture slowly neutralized at the same temperature with NaHCO3 sat. aq. sol. The organic layer was washed with water and brine, dried over Na2SO4, and evaporated. The residue was diluted intBuOH (40 mL) and heated at 82 °C for 2 h. The solvent was removed in vacuo by azeotropic distillation with toluene. Purification by FC (SiO2; CHCl3 / CH3CN) delivered the title compound (1.1 g, 33% yield). MS (ESI): m / z = 273.2 [M+H]+Step d: tert-butyl N-[3,3-difluoro-1-(4-pyridyl)propyl]-N-methyl-carbamate Sodium hydride (60% in mineral oil) (8.08 mg, 0.2 mmol) was added portionwise at 0 °C to a solution of tert-butyl N-[3,3-difluoro-1-(4-pyridyl)propyl]carbamate (50.0 mg, 0.18 mmol) in THF (1 mL).The reaction mixture was stirred for 30 min then iodomethane (10 µL, 0.2 mmol) was added dropwise and the reaction was stirred at 23 °C for 18 h. The reaction was quenched with saturated NH4Cl sol. and extracted with EtOAc (30 mL). The organic phases were washed with water (2 x 50 mL) and brine (30 mL). The organic layers were combined, dried over Na2SO4, filtered and evaporated. Purification by FC (SiO2; heptane / EtOAc) delivered the title compound (30.0 mg, 17% yield) as a dark brown viscous oil. MS (ESI): m / z = 287.2 [M+H]+Step e: [3,3-difluoro-1-(4-pyridyl)propyl]-methyl-ammonium;2,2,2-trifluoroacetate TFA (3.75 mL, 48.56 mmol) was added to a stirred solution of tert-butyl N-[3,3-difluoro-1-(4- pyridyl)propyl]-N-methyl-carbamate (0.68 g, 2.36 mmol) in DCM (7 mL) at 20 °C. The mixture was then stirred at 20 °C for 18 h. The solvent was evaporated to deliver the title compound (1.3 g, 87% yield). MS (ESI): m / z = 187.2 [M+H]+Example 80 1-(difluoromethyl)-3-(4,4-difluorotetrahydrofuran-3-yl)-1-(4-pyridylmethyl)urea In a vial under Argon, N-(4-pyridylmethyl)thioformamide (200.0 mg, 1.31 mmol) was dissolved in CH3CN (5 mL). A solution of AgOCF3in CH3CN (3.94 mL, 3.94 mmol) was added. The mixture was stirred at 50 °C for 2 h. The resulting suspension was diluted with DCM and filtered through Celite. The filtrate was evaporated. The residue was diluted with DCM / CH3CN 1 / 1 (20 mL), filtered of through Celite and concentrated. The residue was dissolved in CH3CN (5 mL), DIPEA (0.92 mL, 5.26 mmol) and (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 209.66 mg, 1.31 mmol) were added. The mixture was stirred at 20 °C for 15 h. The solvent was evaporated. Purification by HPLC (Chromatorex 18, CH3CN / H2O) delivered the title compound (15.9 mg, 4% yield) as a white solid. MS (ESI): m / z = 308.2 [M+H]+Step a: N-(4-pyridylmethyl)formamide To a solution of 4-(aminomethyl)pyridine (CAS RN: 3731-53-1; 1.00 g, 9.25 mmol) in THF (20 mL), (2,5-dioxopyrrolidin-1-yl) formate (CAS RN: 17592-54-0; 1.324 g, 9.25 mmol) was added portionwise at 0 °C. The mixture was stirred at 20 °C for 5 h. The mixture was evaporated. The residue was diluted with CH3CN (10 mL) and TEA (1.5 mL) was added. The precipitated solid was filtered off, and the filtrate evaporated to deliver the title compound (800.0 mg, 57% yield) as a light brown oil. MS (ESI): m / z = 137.0 [M+H]+Step b: N-(4-pyridylmethyl)thioformamide To a solution of N-(4-pyridylmethyl)formamide (800.0 mg, 5.88 mmol) in THF (20 mL), Lawesson reagent (CAS RN: 19172-47-5; 1.307 g, 3.23 mmol) was added in one portion. The mixture was heated at 55 °C for 15 h. The mixture was evaporated. The residue was diluted with water (10 mL) and TEA (2 mL) was added. The resulting solution was extracted with DCM (2×20 mL). The organic layers were dried over Na2SO4, and evaporated.. Purification by RP-HPLC (XBridge BEH C18, H2O / CH3CN+0.1% NH4OH) delivered the title compound (29.0 mg, 3% yield) as a white solid. MS (ESI): m / z = 153.0 [M+H]+Example 81 [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-ethyl-4-pyridyl)ethyl]-1-methyl-urea and 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-ethyl-4-pyridyl)ethyl]-1-methyl- urea] or [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-ethyl-4-pyridyl)ethyl]-1- methyl-urea and 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-ethyl-4-pyridyl)ethyl]- 1-methyl-urea] or [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-ethyl-4- pyridyl)ethyl]-1-methyl-urea and 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-ethyl- 4-pyridyl)ethyl]-1-methyl-urea] or [3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3- ethyl-4-pyridyl)ethyl]-1-methyl-urea and 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1- (3-ethyl-4-pyridyl)ethyl]-1-methyl-urea] or [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)- 1-(3-ethyl-4-pyridyl)ethyl]-1-methyl-urea and 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1- [(1R)-1-(3-ethyl-4-pyridyl)ethyl]-1-methyl-urea] or [3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]- 1-[(1S)-1-(3-ethyl-4-pyridyl)ethyl]-1-methyl-urea and 3-[(3S)-4,4-difluorotetrahydrofuran-3- yl]-1-[(1R)-1-(3-ethyl-4-pyridyl)ethyl]-1-methyl-urea To a solution of (4,4-difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 151.55 mg, 949.77 µmol) in DCM (1.3 mL) were added DIPEA (581 µL, 3.2 mmol) followed by CDT (234 mg, 1.42 mmol). The reaction mixture was stirred at 23 °C for for 1 h. Then, 1-(3-ethyl- 4-pyridyl)ethyl-methyl-amine (156 mg, 950 µmol) was added. The reaction mixture was stirred at 23 °C for 16 h. The organic layers were dried over MgSO4, and evaporated. Purification by SFC (Chiral column Wrr, 5μm, 250 x 20 mm, 15% MeOH) delivered the title compound as a mixture of diastereomers (0.8 mg, 0.25% yield, tR = 1.834 min) and as a colorless oil. MS (ESI): m / z = 412.1 [M+H]+Step a: N-[1-(3-ethyl-4-pyridyl)ethyl]carbamic acid tert-butyl ester To a solution of 1-(3-ethyl-4-pyridyl)ethylamine (CAS RN: 56129-55-6; 500 mg, 3.16 mmol) in DCM (16 mL) was added TEA (1.76 mL, 12.65 mmol) followed by (Boc)2O (1.04 g, 4.74 mmol). The reaction was stirred at 23 °C for 18 h. The reaction was quenched with brine and extracted with DCM. The organic layers were dried over Na2SO4, and evaporated. Purification by FC (SiO2; DCM / MeOH) delivered the title compound (337 mg 41% yield) as an orange gum. MS (ESI): m / z = 251.2 [M+H]+Step b: N-[1-(3-ethyl-4-pyridyl)ethyl]-N-methyl-carbamic acid tert-butyl ester To a solution of N-[1-(3-ethyl-4-pyridyl)ethyl]carbamic acid tert-butyl ester (230 mg, 872.81 µmol) in THF, extra dry (8.73 mL) was added 0.5 M KHMDS (3.49 mL, 1.75 mmol) under Argon at 0 °C and the mixture was stirred for 1 h. Then CH3I (81.86 µL, 1.31 mmol) was added and the reaction stirred at 50 °C for 3 h. The solution was quenched with NH4Cl sat. sol. and extracted with DCM to deliver the title compound (253.1 mg, 88% yield, 80% purity) as a light brown oil. MS (ESI): m / z = 265.2 [M+H]+Step c: 1-(3-ethyl-4-pyridyl)ethyl-methyl-amine To a solution of N-[1-(3-ethyl-4-pyridyl)ethyl]-N-methyl-carbamic acid tert-butyl ester (253.1 mg, 0.957 mmol) in DCM (4.8 mL) was added TFA (737.56 µL, 9.57 mmol). The resulting solution was stirred overnight at 23 °C. The mixture was neutralised with NaOH to pH 8 / 9. The water phase was extracted with DCM and further washed with water. The organic layers were dried over Na2SO4, and evaporated to deliver the title compound (156 mg, 79% yield, 80% purity) as a light brown oil. MS (ESI): m / z = 165.1 [M+H]+ Example 82 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[2,2,2-trifluoro-1-(4-pyridyl)ethyl]urea] Triphosgene (CAS RN: 32315-10-9; 74.9 mg, 0.25 mmol) was dissolved in DCM (6 mL) at 0 °C. (4,4-Difluorotetrahydrofuran-3-yl)amine;hydrochloride (CAS RN: 2408969-70-8; 0.1 g, 0.63 mmol) and DIPEA (0.4 mL, 2.27 mmol) were dissolved in DCM (6 ml) and added dropwise. The reaction mixture was allowed to warm up to 23 °C and stirred for 30 min. After that, the solution was cooled down to 0 °C and a solution of 2,2,2-trifluoro-N-methyl-1-(4-pyridyl)ethanamine (0.12 g, 0.63 mmol) and DIPEA (0.4 mL, 2.27 mmol) in DCM (6 mL) was added dropwise. The mixture was stirred at 20 °C for 18 h. The solvent was evaporated. Purification by RP-HPLC (CROMATOREX SMB C18, CH3CN / H2O) and chiral RP-HPLC (Column Chiralpak AD-H, 250x4.6 mm, 5 µm, 50% / 25% / 25% Hexane / IPA / MeOH) delivered the title compound (4.2 mg, 1.47% yield) as an orange oil. MS (ESI): m / z = 340.2 [M+H]+Step a: 2,2,2-trifluoro-N-methyl-1-(4-pyridyl)ethanamine MeNH2·HCl (CAS RN: 593-51-1; 0.62 g, 9.14 mmol) and TEA (1.27 mL, 9.14 mmol) were added to a stirred solution of 2,2,2-trifluoro-1-(4-pyridyl)ethanone (0.8 g, 4.57 mmol) in THF (15 mL). The solution of Ti(OiPr)4(4.06 mL, 13.71 mmol) was added to the mixture. The reaction was stirred at 70 °C for 16 h. NaBH4 (0.02 g, 0.57 mmol) was added and the reaction stirred at 23 °C for 16 h. The reaction was quenched by reverse adding in NH3·H2O solution (1% in 20 mL of water), extracted with EtOAc (20 mL), and filtered. The organic layers were dried over Na2SO4, and the solvent evaporated. Purification by FC (SiO2; CHCl3 / CH3CN) delivered the title compound (0.1 g, 10% yield) as a light red oil. MS (ESI): m / z = 191.2 [M+H]+Example 83 A compound of formula (I) can be used in a manner known per se as the active ingredient for the production of tablets of the following composition: Per tablet Active ingredient 200 mg Microcrystalline cellulose 155 mg Corn starch 25 mg Talc 25 mg Hydroxypropylmethylcellulose 20 mg 425 mg Example 84 A compound of formula (I) can be used in a manner known per se as the active ingredient for the production of capsules of the following composition: Per capsule Active ingredient 100.0 mg Corn starch 20.0 mg Lactose 95.0 mg Talc 4.5 mg Magnesium stearate 0.5 mg 220.0 mg

Claims

Claims 1. A compound of formula (I)or a pharmaceutically acceptable salt thereof, wherein: X, Y and Z are each selected from CRZand N, provided that at most two of X, Y and Z are N; U is selected from O, S, and NRU; V is a covalent bond or C(RV)2; A is selected from 3- to 14-membered heterocyclyl, 5- to 14-membered heteroaryl, C6-C10-aryl and C3-C10-cycloalkyl; L is selected from a covalent bond, –CH2–, and –NRL–; RLis selected from hydrogen and C1-C6-alkyl; RUis selected from hydrogen, C1-C6-alkyl and cyano; each RVis independently selected from hydrogen, C1-C6-alkyl and halo-C1-C6-alkyl; RZis selected from hydrogen and C1-C6-alkyl; R1is selected from hydrogen, halogen, cyano, C1-C6-alkyl, C2-C6-alkenyl, C2-C6- alkynyl, halo-C1-C6-alkyl, hydroxy-C1-C6-alkyl, C1-C6-alkoxy, halo-C1-C6- alkoxy, and a groupR1ais selected from hydrogen, halogen, C1-C6-alkyl, and halo-C1-C6-alkyl; R2aand R2bare each independently selected from hydrogen, C1-C6-alkyl, halo-C1-C6- alkyl, C1-C6-alkoxy, halo-C1-C6-alkoxy, C1-C6-alkyl-NH-C1-C6-alkyl-, C3-C10- cycloalkyl, C3-C10-cycloalkyl-C1-C6-alkyl, C6-C10-aryl, C6-C10-aryl-C1-C6- alkyl, and R2c-O-C1-C6-alkyl; wherein each C6-C10-aryl and C3-C10-cycloalkyl is optionally substituted with 1-2 halogen substituents or R2aand R2b, taken together with the carbon atom to which they are attached, form a C3-C10-cycloalkyl;R2cis selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, and C6-C10-aryl; wherein said C6-C10-aryl is optionally substituted with 1-2 halogen substituents; R3is selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, and C3-C10- cycloalkyl; R4aand R4bare each independently selected from hydrogen, halogen, hydroxy, C1- C6-alkyl, 5- to 14-membered heteroaryl, C6-C10-aryl, C6-C10-aroyl, 5- to 14- membered heteroaroyl; wherein said 5- to 14-membered heteroaryl, C6-C10- aryl, C6-C10-aroyl, 5- to 14-membered heteroaroyl are optionally substituted with 1-3 substituents independently selected from halogen and hydroxy-C1-C6- alkyl; or R4aand R4b, taken together with the carbon atom to which they are attached, form a C3-C10-cycloalkyl or a 3- to 14-membered heterocyclyl, wherein said C3-C10- cycloalkyl and 3- to 14-membered heterocyclyl are optionally substituted with 1-3 halogen substituents; or R4aand R7, taken together with the carbon atoms to which they are attached, form a C3-C10-cycloalkyl; R5aand R5bare each independently selected from hydrogen and C1-C6-alkyl; or R5aand R5b, taken together with the carbon atom to which they are attached, form a C3-C10-cycloalkyl or oxo; R6aand R6bare each independently selected from hydrogen, 5- to 14-membered heteroaryl, and C6-C10-aryl; wherein said 5- to 14-membered heteroaryl, and C6-C10-aryl are optionally substituted with 1-3 substituents independently selected from halogen, C1-C6-alkyl, halo-C1-C6-alkyl, C3-C10-cycloalkyl, and 5- to 14-membered heteroaryl; and R7is selected hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, and 5- to 14-membered heteroaryl.

2. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, wherein: (i) X and Y are CH and Z is CRZ; wherein RZis selected from hydrogen and C1- C6-alkyl; or (ii) X and Z are CH and Y is N; or (iii) X is N and Y and Z are CH.

3. The compound of formula (I) according to claim 2, or a pharmaceutically acceptable salt thereof, wherein: (i) X, Y are CH and Z is CRZ; wherein RZis selected from hydrogen and methyl; or (ii) X and Z are CH and Y is N.

4. The compound of formula (I) according to claim 3, or a pharmaceutically acceptable salt thereof, wherein X, Y and Z are CH.

5. The compound of formula (I) according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, wherein: R1is selected from hydrogen, halogen, cyano, C1-C6-alkyl, C2-C6-alkynyl, halo- C1-C6-alkyl, hydroxy-C1-C6-alkyl, C1-C6-alkoxy, and a groupA is selected from 3- to 6-membered heterocyclyl comprising 1 to 3 heteroatoms selected from N, O, and S, 5- to 6-membered heteroaryl comprising 1 to 3 heteroatoms selected from N, O, and S, phenyl, and C3-C6-cycloalkyl; L is selected from a covalent bond, –CH2–, and –NRL–; RLis hydrogen; and R1ais selected from hydrogen, halogen, C1-C6-alkyl, and halo-C1-C6-alkyl.

6. The compound of formula (I) according to claim 5, or a pharmaceutically acceptable salt thereof, wherein: R1is selected from hydrogen, fluoro, chloro, bromo, cyano, methyl, ethyl, prop-1- ynyl, hydroxymethyl, CHF2, methoxy, and a group; A is selected from azetidine, tetrahydrofurane, tetrahydropyrane, pyrrolidine, pyrazole, phenyl, pyridyl, and cyclopropyl; L is selected from a covalent bond, –CH2–, and –NRL–; RLis hydrogen; and R1ais selected from hydrogen, chloro, methyl, and CF3.

7. The compound of formula (I) according to claim 5, or a pharmaceutically acceptable salt thereof, wherein R1is selected from hydrogen, halogen, and C1-C6-alkyl.

8. The compound of formula (I) according to claim 7, or a pharmaceutically acceptable salt thereof, wherein R1is selected from hydrogen, fluoro, and methyl.

9. The compound of formula (I) according to any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof, wherein: R2ais selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, C1-C6-alkyl-NH-C1- C6-alkyl-, C3-C10-cycloalkyl, phenyl-C1-C6-alkyl, and R2c-O-C1-C6-alkyl; wherein said phenyl is optionally substituted with 1 halogen substituent; R2bis hydrogen; and R2cis selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, and phenyl; wherein said phenyl is optionally substituted with 1 halogen substituent; or R2aand R2b, taken together with the carbon atom to which they are attached, form a C3-C6-cycloalkyl.

10. The compound of formula (I) according to claim 9, or a pharmaceutically acceptable salt thereof, wherein: R2ais selected from hydrogen, methyl, ethyl, CH2F, CHF2, CF3, CH2CHF2, CH3N- CH2-, hydroxymethyl, methoxymethyl, phenoxymethyl, chlorophenoxymethyl, fluorophenylethyl, CHF2-O-CH2-, CF3-O-CH2-, and cyclopropyl; and R2bis hydrogen; or R2aand R2b, taken together with the carbon atom to which they are attached, form a cyclopropyl or a cyclobutyl.

11. The compound of formula (I) according to claim 8, or a pharmaceutically acceptable salt thereof, wherein: R2ais C1-C6-alkyl; and R2bis hydrogen.

12. The compound of formula (I) according to claim 10, or a pharmaceutically acceptable salt thereof, wherein: R2ais methyl; and R2bis hydrogen.

13. The compound of formula (I) according to any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, wherein R3is selected from C1-C6-alkyl and halo-C1-C6-alkyl.

14. The compound of formula (I) according to any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, wherein R3is selected from methyl and CHF2.

15. The compound of formula (I) according to claim 13, or a pharmaceutically acceptable salt thereof, wherein R3is C1-C6-alkyl.

16. The compound of formula (I) according to claim 15, or a pharmaceutically acceptable salt thereof, wherein R3is methyl.

17. The compound of formula (I) according to any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, wherein: R4ais selected from hydrogen, halogen, hydroxy, C1-C6-alkyl, 5- to 14-membered heteroaryl, and C6-C10-aroyl; wherein said 5- to 14-membered heteroaryl is optionally substituted with 1 substituent selected from halogen and hydroxy- C1-C6-alkyl; and R4bis selected from hydrogen, halogen, and C1-C6-alkyl; or R4aand R4b, taken together with the carbon atom to which they are attached, form a C3-C10-cycloalkyl; or R4aand R7, taken together with the carbon atoms to which they are attached, form a C3-C6-cycloalkyl; R5aand R5bare each independently selected from hydrogen and C1-C6-alkyl; or R5aand R5b, taken together with the carbon atom to which they are attached, form a C3-C10-cycloalkyl or oxo; R6ais selected from hydrogen, 5- to 14-membered heteroaryl, and C6-C10-aryl; wherein said 5- to 14-membered heteroaryl, and C6-C10-aryl are substituted with 1-3 substituents independently selected from halogen, C1-C6-alkyl, C3- C10-cycloalkyl, and 5- to 14-membered heteroaryl; R6bis hydrogen; and R7is selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, and 5- to 14- membered heteroaryl.

18. The compound of formula (I) according to claim 17, or a pharmaceutically acceptable salt thereof, wherein: R4ais selected from hydrogen, fluoro, hydroxy, methyl, benzoyl, pyridyl, triazolyl, 1,2,4-triazolyl, and pyrazolyl; wherein said pyridyl, triazolyl, 1,2,4-triazolyl, and pyrazolyl is optionally substituted with 1 substituent selected from chloro, bromo, and hydroxymethyl; and R4bis selected from hydrogen, fluoro, and methyl; or R4aand R4b, taken together with the carbon atom to which they are attached, form a cyclopropyl; or R4aand R7, taken together with the carbon atoms to which they are attached, form a cyclopropyl; R5aand R5bare each independently selected from hydrogen and methyl; or R5aand R5b, taken together with the carbon atom to which they are attached, form a cyclopropyl or oxo; R6ais selected from hydrogen, pyrazolyl, pyridyl, pyridazinyl, isoxazolyl, 1,2,4- oxadiazolyl, and phenyl; wherein said pyrazolyl, pyridyl, pyridazinyl, isoxazolyl, 1,2,4-oxadiazolyl, and phenyl are substituted with 1-3 substituents independently selected from fluoro, chloro, bromo, methyl, cyclopropyl, and pyridyl; R6bis hydrogen; and R7is selected from hydrogen, methyl, CHF2, CF3, and imidazolyl.

19. The compound of formula (I) according to claim 17, or a pharmaceutically acceptable salt thereof, wherein: R4ais selected from hydrogen, halogen, and C1-C6-alkyl; R4bis selected from hydrogen and halogen; R5ais hydrogen; R5bis hydrogen; R6ais selected from hydrogen and 5- to 14-membered heteroaryl; wherein said 5- to 14-membered heteroaryl is substituted with 1 substituent selected from halogen, C1-C6-alkyl, C3-C10-cycloalkyl, and 5- to 14-membered heteroaryl; R6bis hydrogen; and R7is selected from hydrogen, halo-C1-C6-alkyl, and 5- to 14-membered heteroaryl.

20. The compound of formula (I) according to claim 19, or a pharmaceutically acceptable salt thereof, wherein: R4ais selected from hydrogen, fluoro, and methyl; R4bis selected from hydrogen and fluoro; R5ais hydrogen; R5bis hydrogen; R6ais selected from hydrogen, pyridyl, and pyrazolyl; wherein said pyridyl and pyrazolyl are substituted with 1 substituent selected from bromo, methyl, cyclopropyl, and pyridyl; R6bis hydrogen; and R7is selected from hydrogen, CF3, and imidazolyl.

21. The compound of formula (I) according to any one of claims 1 to 20, or a pharmaceutically acceptable salt thereof, wherein: U is selected from O, S, and NRU; V is a covalent bond or CHRV; RUis cyano; and RVis halo-C1-C6-alkyl.

22. The compound of formula (I) according to claim 21, or a pharmaceutically acceptable salt thereof, wherein: U is selected from O, S, and NRU; V is a covalent bond or CHRV; RUis cyano; and RVis CF3.

23. The compound of formula (I) according to claim 22, or a pharmaceutically acceptable salt thereof, wherein U is O and V is a covalent bond, represented by Formula (Ia):wherein X, Y, Z, and R1to R7are as defined in any one of claims 1 to 20.

24. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, wherein: (i) X and Y are CH and Z is CRZ; or (ii) X and Z are CH and Y is N; or (iii) X is N and Y and Z are CH; U is selected from O, S, and NRU; V is a covalent bond or CHRV; A is selected from 3- to 6-membered heterocyclyl comprising 1 to 3 heteroatoms selected from N, O, and S, 5- to 6-membered heteroaryl comprising 1 to 3 heteroatoms selected from N, O, and S, phenyl, and C3-C6-cycloalkyl; L is selected from a covalent bond, –CH2–, and –NRL–; RLis hydrogen; RUis cyano; RVis halo-C1-C6-alkyl; RZis selected from hydrogen and C1-C6-alkyl; R1is selected from hydrogen, halogen, cyano, C1-C6-alkyl, C2-C6-alkynyl, halo- C1-C6-alkyl, hydroxy-C1-C6-alkyl, C1-C6-alkoxy, and a groupR1ais selected from hydrogen, halogen, C1-C6-alkyl, and halo-C1-C6-alkyl; R2ais selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, C1-C6-alkyl-NH-C1- C6-alkyl-, C3-C10-cycloalkyl, phenyl-C1-C6-alkyl, and R2c-O-C1-C6-alkyl; wherein said phenyl is optionally substituted with 1 halogen substituent; R2bis hydrogen; and R2cis selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, and phenyl; wherein said phenyl is optionally substituted with 1 halogen substituent; or R2aand R2b, taken together with the carbon atom to which they are attached, form a C3-C6-cycloalkyl; R3is selected from C1-C6-alkyl and halo-C1-C6-alkyl; R4ais selected from hydrogen, halogen, hydroxy, C1-C6-alkyl, 5- to 14-membered heteroaryl, and C6-C10-aroyl; wherein said 5- to 14-membered heteroaryl isoptionally substituted with 1 substituent selected from halogen and hydroxy- C1-C6-alkyl; and R4bis selected from hydrogen, halogen, and C1-C6-alkyl; or R4aand R4b, taken together with the carbon atom to which they are attached, form a C3-C10-cycloalkyl; or R4aand R7, taken together with the carbon atoms to which they are attached, form a C3-C6-cycloalkyl; R5aand R5bare each independently selected from hydrogen and C1-C6-alkyl; or R5aand R5b, taken together with the carbon atom to which they are attached, form a C3-C10-cycloalkyl or oxo; R6ais selected from hydrogen, 5- to 14-membered heteroaryl, and C6-C10-aryl; wherein said 5- to 14-membered heteroaryl, and C6-C10-aryl are substituted with 1-3 substituents independently selected from halogen, C1-C6-alkyl, C3- C10-cycloalkyl, and 5- to 14-membered heteroaryl; R6bis hydrogen; and R7is selected from hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, and 5- to 14- membered heteroaryl.

25. The compound of formula (I) according to claim 24, or a pharmaceutically acceptable salt thereof, wherein: (i) X and Y are CH and Z is CRZ; or (ii) X and Z are CH and Y is N; or (iii) X is N and Y and Z are CH; U is selected from O, S, and NRU; V is a covalent bond or CHRV; A is selected from azetidine, tetrahydrofurane, tetrahydropyrane, pyrrolidine, pyrazole, phenyl, pyridyl, and cyclopropyl; L is selected from a covalent bond, –CH2–, and –NRL–; RLis hydrogen; RUis cyano; RVis CF3; RZis selected from hydrogen and methyl;R1is selected from hydrogen, fluoro, chloro, bromo, cyano, methyl, ethyl, prop-1- ynyl, hydroxymethyl, CHF2, methoxy, and a group;; R1ais selected from hydrogen, chloro, methyl, and and CF3; R2ais selected from hydrogen, methyl, ethyl, CH2F, CHF2, CF3, CH2CHF2, CH3N- CH2-, hydroxymethyl, methoxymethyl, phenoxymethyl, chlorophenoxymethyl, fluorophenylethyl, CHF2-O-CH2-, CF3-O-CH2-, and cyclopropyl; and R2bis hydrogen; or R2aand R2b, taken together with the carbon atom to which they are attached, form a cyclopropyl or a cyclobutyl; R3is selected from methyl and CHF2; R4ais selected from hydrogen, fluoro, hydroxy, methyl, benzoyl, pyridyl, triazolyl, 1,2,4-triazolyl, and pyrazolyl; wherein said pyridyl, triazolyl, 1,2,4-triazolyl, and pyrazolyl is optionally substituted with 1 substituent selected from chloro, bromo, and hydroxymethyl; and R4bis selected from hydrogen, fluoro, and methyl; or R4aand R4b, taken together with the carbon atom to which they are attached, form a cyclopropyl; or R4aand R7, taken together with the carbon atoms to which they are attached, form a cyclopropyl; R5aand R5bare each independently selected from hydrogen and methyl; or R5aand R5b, taken together with the carbon atom to which they are attached, form a cyclopropyl or oxo; R6ais selected from hydrogen, pyrazolyl, pyridyl, pyridazinyl, isoxazolyl, 1,2,4- oxadiazolyl, and phenyl; wherein said pyrazolyl, pyridyl, pyridazinyl, isoxazolyl, 1,2,4-oxadiazolyl, and phenyl are substituted with 1-3 substituents independently selected from fluoro, chloro, bromo, methyl, cyclopropyl, and pyridyl; R6bis hydrogen; and R7is selected from hydrogen, methyl, CHF2, CF3, and imidazolyl.

26. The compound of formula (I) according to claim 24, or a pharmaceutically acceptable salt thereof, wherein:(i) X, Y and Z are CH; or (ii) X and Z are CH and Y is N; U is O; V is a covalent bond; R1is selected from hydrogen, halogen, and C1-C6-alkyl; R2ais C1-C6-alkyl; and R2bis hydrogen; R3is C1-C6-alkyl; R4ais selected from hydrogen, halogen, and C1-C6-alkyl; R4bis selected from hydrogen and halogen; R5ais hydrogen; R5bis hydrogen; R6ais selected from hydrogen and 5- to 14-membered heteroaryl; wherein said 5- to 14-membered heteroaryl is substituted with 1 substituent selected from halogen, C1-C6-alkyl, C3-C10-cycloalkyl, and 5- to 14-membered heteroaryl; R6bis hydrogen; and R7is selected from hydrogen, halo-C1-C6-alkyl, and 5- to 14-membered heteroaryl.

27. The compound of formula (I) according to claim 26, or a pharmaceutically acceptable salt thereof, wherein: (i) X, Y and Z are CH; or (ii) X and Z are CH and Y is N; U is O; V is a covalent bond; R1is selected from hydrogen, fluoro, and methyl; R2ais methyl; and R2bis hydrogen; R3is methyl; R4ais selected from hydrogen, fluoro, and methyl; R4bis selected from hydrogen and fluoro; R5ais hydrogen; R5bis hydrogen;R6ais selected from hydrogen, pyridyl, and pyrazolyl; wherein said pyridyl and pyrazolyl are substituted with 1 substituent selected from bromo, methyl, cyclopropyl, and pyridyl; R6bis hydrogen; and R7is selected from hydrogen, CF3, and imidazolyl.

28. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, wherein said compound of formula (I) is selected from: 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(3RS)-tetrahydrofuran-3-yl]urea; 1-methyl-3-[(3RS, 4RS)-4-methyltetrahydrofuran-3-yl]-1-[(1S)-1-(4- pyridyl)ethyl]urea; 1-methyl-3-[(3RS, 4SR)-4-methyltetrahydrofuran-3-yl]-1-[(1S)-1-(4- pyridyl)ethyl]urea; 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(3RS)-3-(trifluoromethyl)tetrahydrofuran-3- yl]urea; 3-[(3RS)-3-(1H-imidazol-2-yl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea; 1-methyl-3-[(3RS)-3-(1-methylpyrazol-4-yl)tetrahydrofuran-3-yl]-1-[(1S)-1-(4- pyridyl)ethyl]urea; 3-[(2RS,3SR)-2-(5-bromo-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea; 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(2RS,3SR)-2-[5-(3-pyridyl)-3- pyridyl]tetrahydrofuran-3-yl]urea; 3-[(2RS,3SR)-2-(5-cyclopropyl-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1- (4-pyridyl)ethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea; 3-[(2S,3R)-2-(5-bromo-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea; 3-[(2R,3S)-2-(5-bromo-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea;1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(2R,3S)-2-[5-(3-pyridyl)-3- pyridyl]tetrahydrofuran-3-yl]urea; 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(2S,3R)-2-[5-(3-pyridyl)-3- pyridyl]tetrahydrofuran-3-yl]urea; 3-[(2R,3S)-2-(5-cyclopropyl-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea; 3-[(2S,3R)-2-(5-cyclopropyl-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea; 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-(2,2,2-trifluoro-1-tetrahydrofuran-3-yl- ethyl)urea; 1-[(3-chloro-4-pyridyl)methyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-[(3-fluoro-4-pyridyl)methyl]-1-methyl-urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-(4-pyridylmethyl)urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)propyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-(4- pyridyl)propyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)propyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-(4- pyridyl)propyl]urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[(3-methyl-4-pyridyl)methyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyridazin-4- ylethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyridazin-4- ylethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyridazin-4- ylethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyridazin-4- ylethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyridazin-4- ylethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyridazin-4- ylethyl]urea;3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyridazin-4- ylethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyridazin-4- ylethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyridazin-4- ylethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyridazin-4- ylethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyridazin-4- ylethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyridazin-4- ylethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-(4-pyridylmethyl)urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-(4-pyridylmethyl)urea; 3-(4-benzoyltetrahydrofuran-3-yl)-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]urea; 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(3R)-3-(trifluoromethyl)tetrahydrofuran-3- yl]urea; 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(3S)-3-(trifluoromethyl)tetrahydrofuran-3- yl]urea; 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(3R)-3-(trifluoromethyl)tetrahydrofuran-3- yl]urea; 1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]-3-[(3S)-3-(trifluoromethyl)tetrahydrofuran-3- yl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(3-methyl-4- pyridyl)methyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(3-methyl-4- pyridyl)methyl]urea; 1-[(3-bromo-4-pyridyl)methyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyrimidin-4- ylethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyrimidin-4- ylethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-pyrimidin-4- ylethyl]urea;3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-pyrimidin-4- ylethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-fluoro-4-pyridyl)ethyl]-1- methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-fluoro-4-pyridyl)ethyl]-1- methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-fluoro-4-pyridyl)ethyl]-1- methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-fluoro-4-pyridyl)ethyl]-1- methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-fluoro-4-pyridyl)ethyl]-1- methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-fluoro-4-pyridyl)ethyl]-1- methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-fluoro-4-pyridyl)ethyl]-1- methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-fluoro-4-pyridyl)ethyl]-1- methyl-urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-[[3-(hydroxymethyl)-4-pyridyl]methyl]-1- methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(3-methyl-4- pyridyl)ethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-(3-methyl-4- pyridyl)ethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(3-methyl-4- pyridyl)ethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-1-(3-methyl-4- pyridyl)ethyl]urea; 1-[(3-cyclopropyl-4-pyridyl)methyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl- urea; 1-[(3-bromo-4-pyridyl)methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl- urea; 1-[(3-bromo-4-pyridyl)methyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl- urea;1-[[3-(azetidin-1-yl)-4-pyridyl]methyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1- methyl-urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[2-phenoxy-1-(4-pyridyl)ethyl]urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-[2-methoxy-1-(4-pyridyl)ethyl]-1-methyl- urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-[(3-methoxy-4-pyridyl)methyl]-1-methyl- urea; 1-[1-(3-chloro-4-pyridyl)ethyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[(3-pyrrolidin-1-yl-4- pyridyl)methyl]urea; 1-[(S)-cyclopropyl(4-pyridyl)methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea; 1-[(S)-cyclopropyl(4-pyridyl)methyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea; 1-[(R)-cyclopropyl(4-pyridyl)methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea; 1-[(R)-cyclopropyl(4-pyridyl)methyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[1-(4-pyridyl)cyclopropyl]urea; 3-[(2R,3S)-2-(5-bromo-2-methyl-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)- 1-(4-pyridyl)ethyl]urea; 3-[(2S,3R)-2-(5-bromo-2-methyl-3-pyridyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)- 1-(4-pyridyl)ethyl]urea; 1-[(1S)-1-(3-chloro-4-pyridyl)ethyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea; 1-[(1S)-1-(3-chloro-4-pyridyl)ethyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea; 1-[(1R)-1-(3-chloro-4-pyridyl)ethyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea; 1-[(1R)-1-(3-chloro-4-pyridyl)ethyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[1-(4- pyridyl)cyclopropyl]urea;3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[1-(4- pyridyl)cyclopropyl]urea; 1-[[3-(3-chloroanilino)-4-pyridyl]methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]- 1-methyl-urea; 1-[[3-(3-chloroanilino)-4-pyridyl]methyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]- 1-methyl-urea; 3-[(3S)-4,4-difluoro-3-methyl-tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea; 3-[(3R)-4,4-difluoro-3-methyl-tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-2-phenoxy-1-(4- pyridyl)ethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-2-phenoxy-1-(4- pyridyl)ethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1R)-2-phenoxy-1-(4- pyridyl)ethyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(1S)-2-phenoxy-1-(4- pyridyl)ethyl]urea; 1-methyl-3-[(1R,5R)-3-oxabicyclo[3.1.0]hexan-1-yl]-1-[(1S)-1-(4- pyridyl)ethyl]urea; 1-methyl-3-[(1S,5S)-3-oxabicyclo[3.1.0]hexan-1-yl]-1-[(1S)-1-(4-pyridyl)ethyl]urea; 1-methyl-3-[(1R,5R)-3-oxabicyclo[3.1.0]hexan-1-yl]-1-[(1S)-1-(4- pyridyl)ethyl]urea; 1-methyl-3-[(1S,5S)-3-oxabicyclo[3.1.0]hexan-1-yl]-1-[(1S)-1-(4-pyridyl)ethyl]urea; 1-[[3-(difluoromethyl)-4-pyridyl]methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]- 1-methyl-urea; 1-[[3-(difluoromethyl)-4-pyridyl]methyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]- 1-methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[1-(4-pyridyl)cyclobutyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[1-(4-pyridyl)cyclobutyl]urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[[3-(1H-pyrazol-5-yl)-4- pyridyl]methyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-2-hydroxy-1-(4-pyridyl)ethyl]-1- methyl-urea;3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-2-hydroxy-1-(4-pyridyl)ethyl]-1- methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-2-hydroxy-1-(4-pyridyl)ethyl]-1- methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-2-hydroxy-1-(4-pyridyl)ethyl]-1- methyl-urea; 3-[3-(difluoromethyl)tetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(3-phenyl-4- pyridyl)methyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[(3-phenyl-4- pyridyl)methyl]urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[(1S)-1-(4-pyridyl)ethyl]thiourea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[[3-(3-methyl-1H-pyrazol-5-yl)-4- pyridyl]methyl]urea; 2-cyano-3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]guanidine; 1-methyl-3-(5-oxotetrahydrofuran-3-yl)-1-[(1S)-1-(4-pyridyl)ethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-[[(3S)-tetrahydrofuran-3- yl]methyl]-4-pyridyl]methyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-[[(3R)-tetrahydrofuran-3- yl]methyl]-4-pyridyl]methyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-[[(3S)-tetrahydrofuran-3- yl]methyl]-4-pyridyl]methyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-[[(3R)-tetrahydrofuran-3- yl]methyl]-4-pyridyl]methyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-(4-pyridyl)-4- pyridyl]methyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-(3-pyridyl)-4- pyridyl]methyl]urea; 1-[[3-(4-chlorophenyl)-4-pyridyl]methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]- 1-methyl-urea; 1-[[3-(2-chlorophenyl)-4-pyridyl]methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]- 1-methyl-urea;1-[[3-(3-chlorophenyl)-4-pyridyl]methyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]- 1-methyl-urea; 1-[2-(3-chlorophenoxy)-1-(4-pyridyl)ethyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1- methyl-urea; 3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[(3-prop-1-ynyl-4- pyridyl)methyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-(2-pyridyl)-4- pyridyl]methyl]urea; 1-[2-(4-chlorophenoxy)-1-(4-pyridyl)ethyl]-3-(4,4-difluorotetrahydrofuran-3-yl)-1- methyl-urea; 3-[(3S,4R)-4-hydroxytetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea; 3-[(3R,4S)-4-hydroxytetrahydrofuran-3-yl]-1-methyl-1-[(1S)-1-(4- pyridyl)ethyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-(tetrahydropyran-4- ylmethyl)-4-pyridyl]methyl]urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-(tetrahydropyran-4- ylmethyl)-4-pyridyl]methyl]urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-methyl-1-[[3-[4- (trifluoromethyl)phenyl]-4-pyridyl]methyl]urea; [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3,5-dimethyl-4-pyridyl)ethyl]- 1-methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3,5-dimethyl-4-pyridyl)ethyl]- 1-methyl-urea]; [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3,5-dimethyl-4-pyridyl)ethyl]- 1-methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3,5-dimethyl-4-pyridyl)ethyl]- 1-methyl-urea]; [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3,5-dimethyl-4-pyridyl)ethyl]- 1-methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3,5-dimethyl-4-pyridyl)ethyl]- 1-methyl-urea]; [3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3,5-dimethyl-4-pyridyl)ethyl]- 1-methyl-urea;3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3,5-dimethyl-4-pyridyl)ethyl]- 1-methyl-urea]; [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3,5-dimethyl-4-pyridyl)ethyl]- 1-methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3 yl]-1-[(1R)-1-(3,5-dimethyl-4-pyridyl)ethyl]- 1-methyl-urea]; [3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3,5-dimethyl-4-pyridyl)ethyl]- 1-methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3,5-dimethyl-4-pyridyl)ethyl]- 1-methyl-urea]; 1-[(1S)-1-(3-bromo-4-pyridyl)ethyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea; 1-[(1S)-1-(3-bromo-4-pyridyl)ethyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea; 1-[(1R)-1-(3-bromo-4-pyridyl)ethyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea; 1-[(1R)-1-(3-bromo-4-pyridyl)ethyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1- methyl-urea; 1-[(1R)-2-(4-chlorophenoxy)-1-(4-pyridyl)ethyl]-3-[(3S)-4,4- difluorotetrahydrofuran-3-yl]-1-methyl-urea; 1-[(1R)-2-(4-chlorophenoxy)-1-(4-pyridyl)ethyl]-3-[(3R)-4,4- difluorotetrahydrofuran-3-yl]-1-methyl-urea; 1-[(1S)-2-(4-chlorophenoxy)-1-(4-pyridyl)ethyl]-3-[(3R)-4,4- difluorotetrahydrofuran-3-yl]-1-methyl-urea; 1-[(1S)-2-(4-chlorophenoxy)-1-(4-pyridyl)ethyl]-3-[(3S)-4,4- difluorotetrahydrofuran-3-yl]-1-methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-3-(4-fluorophenyl)-1-(4- pyridyl)propyl]-1-methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-3-(4-fluorophenyl)-1-(4- pyridyl)propyl]-1-methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-3-(4-fluorophenyl)-1-(4- pyridyl)propyl]-1-methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-3-(4-fluorophenyl)-1-(4- pyridyl)propyl]-1-methyl-urea;1-[(1S)-3,3-difluoro-1-(4-pyridyl)propyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]- 1-methyl-urea; 1-[(1S)-3,3-difluoro-1-(4-pyridyl)propyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]- 1-methyl-urea; 1-[(1R)-3,3-difluoro-1-(4-pyridyl)propyl]-3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]- 1-methyl-urea; 1-[(1R)-3,3-difluoro-1-(4-pyridyl)propyl]-3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]- 1-methyl-urea; 1-(difluoromethyl)-3-(4,4-difluorotetrahydrofuran-3-yl)-1-(4-pyridylmethyl)urea; [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-ethyl-4-pyridyl)ethyl]-1- methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-ethyl-4-pyridyl)ethyl]-1- methyl-urea]; [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-ethyl-4-pyridyl)ethyl]-1- methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-ethyl-4-pyridyl)ethyl]-1- methyl-urea]; [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-ethyl-4-pyridyl)ethyl]-1- methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-ethyl-4-pyridyl)ethyl]-1- methyl-urea]; [3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-ethyl-4-pyridyl)ethyl]-1- methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-ethyl-4-pyridyl)ethyl]-1- methyl-urea]; [3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-ethyl-4-pyridyl)ethyl]-1- methyl-urea; 3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-ethyl-4-pyridyl)ethyl]-1- methyl-urea]; [3-[(3R)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1S)-1-(3-ethyl-4-pyridyl)ethyl]-1- methyl-urea; 3-[(3S)-4,4-difluorotetrahydrofuran-3-yl]-1-[(1R)-1-(3-ethyl-4-pyridyl)ethyl]-1- methyl-urea]; and3-(4,4-difluorotetrahydrofuran-3-yl)-1-methyl-1-[2,2,2-trifluoro-1-(4- pyridyl)ethyl]urea].

29. The compound of formula (I) according to any one of claims 1 to 28, or a pharmaceutically acceptable salt thereof, for use as a therapeutically active substance.

30. A pharmaceutical composition comprising a compound of formula (I) according to any one of claims 1 to 28, or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

31. A method of treating or preventing a condition associated with SARM1 in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the compound according to any one of claims 1 to 28, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 30.

32. The method according to claim 31, wherein said condition associated with SARM1 is a condition affecting the nervous system, including the central nervous system and the peripheral nervous system.

33. The method according to claim 32, wherein said condition affecting the nervous system is neurodegenerative disorder.

34. The method according to claim 31, wherein said condition associated with SARM1 is selected from amyotrophic lateral sclerosis, spinal muscular atrophy, chemotherapy induced peripheral neuropathy, diabetes induced peripheral neuropathy, multiple sclerosis, Parkinson's disease, glaucoma, stroke, traumatic brain injury, and Charcot-Marie-Tooth disease.

35. A compound according to any one of claims 1 to 28, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 30, for use in a method according to any one of claims 31 to 34.

36. Use of a compound according to any one of claims 1 to 28, or of a pharmaceutically acceptable salt thereof, or of a pharmaceutical composition according to claim 30, in a method according to any one of claims 31 to 34.

37. Use of a compound according to any one of claims 1 to 28, or of a pharmaceutically acceptable salt thereof, in the preparation of a medicament for use in a method according to any one of claims 31 to 34.

38. A process of manufacturing a compound of formula (Ia) according to claim 23, or a pharmaceutically acceptable salt thereof, comprising: reacting a first amine 1, wherein R4a, R4b, R5a, R5b, R6a, R6b, and R7are as defined in any one of claims 1 to 28,1 with a second amine 3, wherein R1, R2a, R2b, R3, X, Y, and Z are as defined in any one of claims 1 to 28,in the presence of a base and a urea forming reagent, to form said compound of formula (Ia).

39. A compound of formula (I) according to any one of claims 1 to 28, when manufactured according to the process of claim 38.

40. The invention as described hereinbefore.

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