Substituted imidazoles as inhibitors of nav1.8

Abstract

The invention relates to compounds according to general formula (I) which act as inhibitors of NaV1.8 and can be used in the treatment of pain.

Description

[0001] 1 GRA 4216-foreign filing __________________________________________________________________________________ Substituted imidazoles as inhibitors of NaV1.8 __________________________________________________________________________________ The invention relates to compounds according to general formula (I) which act as inhibitors of NaV1.8 and can be used in the treatment of pain. Normal pain sensation (nociception) serves primarily as a survival mechanism, the body^s way of self-protection, alerting against (further) tissue damage and disease from noxious stimuli. For instance, acute pain can arise when the external environment (temperature, pressure, chemicals) activates modality specific receptors (nociceptors) and ion channels within the skin. The peripheral terminals of pain-signaling neurons ^ whose cell bodies are found in the dorsal root ganglia [DRG] and trigeminal ganglia [TG] ^ convert the external stimuli into electrochemical generator potentials. Specific voltage-gated sodium channels (NaVs) integrate and amplify these generator signals until the threshold for an action potential [AP] is reached. Thus, what starts as a noxious stimuli in the periphery eventually leads to action potential firing that travels towards the central nervous system, synapsing first onto neurons in the spinal cord and then towards the brain. NaVs also function to support propagation of action potentials to the central terminals within the spinal cord. At the end of its travels along the somatosensory pathway, the action potential signal is interpreted as pain by the brain (Lumpkin and Caterina, Nature (2007), Vol.445 pp 858-865; and Crawford and Caterina Toxicologic Pathology (2020) 48(1)-174; Goodwin G and McMahon S.B. Nature Re- views Neuroscience (2021) Vol 22 pp 263-274; Bennett D.L. et al. Physiol Rev 99 (2019) Vol 99 pp 1079-1151). Abnormal persistent neuropathic pain arises as a consequence of a lesion or disease of this somatosensory pathway. In response to nerve injury or inflammation, abnormal changes in ion channel expression can cause hyper-excita- bility of pain-signaling neurons and their nerves / axons, thus resulting in pathological pain. The voltage-gated NaV1.8 sodium channel is a therapeutic target for analgesia because of its restricted expression profile (almost exclusive to peripheral sensory tissues), its placement along the pain pathway (free nerve endings, sciatic nerve, and DRG), prominent physiological role in pain signaling (supports upstroke of AP and facilitates repetitive AP firing), and supporting genetic / pharmaco-phenotypic evidence (human / animal studies showing changes in NaV1.8 function cause parallel changes in pain sensitivity). Regarding its expression profile along the pain pathway, because NaV1.8 was first found predominantly in periph- eral sensory neurons of the dorsal root ganglia (DRG) and trigeminal ganglia (TG), it was originally termed SNS (sensory neuron specific) (Akopian A.N. et al Nature (1996) Vol 379 pp 257-261) or PN3 (peripheral nerve 3) 2 GRA 4216-foreign filing (Sangameswaran L. et al J. Biol. Chem. (1996) Vol 271 pp 5953-5956). As well, NaV1.8 is localized at free nerve endings, where pain signaling is initiated in the skin (Persson A.K. et al Mol. Pain. (2010) 6:84) and is diffusely localized along the entire length of non-myelinated axons of sciatic nerve (Rush A.M. et al. Eur.J.Neurosci (2005) Vol 22 pp 39-49). In contrast, NaV1.8 has minimal expression in nonneuronal tissue, such as heart and skeletal muscle, and in the CNS, including brain and spinal cord (9, 10, 338, 406) (Akopian A.N. op. cit.; Akopian A.N. et al. Nat. Neurosci (1999) Vol 2 pp 541-548; Novakovic S.D. et al. J. Neurosci. (1998) Vol 18, pp 2174-2187; and Sagameswaran L. op. cit.). Regarding its physiological role, NaV1.8 contributes the majority of the inward current during the rising phase of an all-or-none action potential in nociceptive sensory neurons (Blair N.T. et al. J. Neurosci. (2003) Vol 23 pp 10338-10350 and Renganathan M et al. J. Neurophysiol (2001) Vol 86 pp 629-640) ^ and also contributes most of the current in subsequent spikes during repetitive firing in DRG neurons (Choi J.S. J. Neurophysiol (2011) Vol 106 pp 3173-3184; and Tan Z.Y. et al. J. Neurosci. (2014) Vol 34 pp 7190-7197). Regarding genetic and pharmacology studies, gain-of-function mutations in NaV1.8 were found in patients with chronic neuropathic pain such as small fiber neuropathy (Faber C.G. et al. (2012) Ann. Neurol Vol 71 pp 26-39; Han C et al. J. Neurol Neurosurg Psychiatry (2014) Vol 85 pp 499-505; and, Kist A.M. et al. PLoS One (2016) Vol 11 e0161789); Eijkenboom I. et al J. Neurol Neurosurg Psychiatry (2019) 90 (3) pp 342-352); loss-of-function (gene knockout) studies in mice reduced pain sensitivity, notably in nociception (Laird J.M. et al. J. Neurosci (2002) J. Neurosci Vol 22 pp 8352-8356; Jarvis M.F. et al Proc Natl Acad Sci USA (2007) Vol 104 pp 8520-8525; Joshi S.K. et al Pain (2006) Vol 123 pp 75-82) and in neuropathic models (Roza C. et al J Physiol (2003) Vol 550 pp 921-926); NaV1.8-selective small molecule inhibitors reduced pain in rodents, specifically in inflammatory and neuropathic models (Jarvis et al. op. cit.; Kort M.E. et al Bioorg Med Chem Lett (2010) Vol 20 pp 6812-6815; Scanio M.J. et al Bioorg Med Chem (2010) Vol 18 pp 7816-7825; Payne C.E. et al Br J Pharmacol (2015) Vol 172 pp 2654-2670). Currently, non-selective NaV channel inhibitors are used to treat epilepsy, cardiac arrhythmia, and chronic pain (Hille, B. J. Gen. Physiol. (1977) Vol.69 pp.497-515; Hille. B, Ion Channels of Excitable Membranes (1992) pp. 391-421; Sunderland, Mass., Sinauer Associates, Inc. 3rded.; Hondeghem L.M. and Katzung B.G. Annu. Rev. Pharmacol. Toxicol. (1984) Vol.24. Pp.387-423; Catterall W.A. Trends Pharmacol. Sci. (1987) Vol.8 pp.57-65) ^ however, all of these analgesics have limited efficacy owing to dose-limiting adverse side-effects related to inhibiting NaV1.1 / NaV1.2 / 1.6 (seizure liability), inhibiting NaV1.4 (muscle weakness / paralysis), inhibiting NaV1.5 (arrhythmia risk). There is a need to develop a NaV1.8-selective small molecule inhibitor as an effective and safe analgesic. It was an object of the invention to provide novel compounds which are inhibitors, preferably selective inhibitors, of NaV1.8, and which preferably have advantages over the compounds of the prior art. The novel compounds should in particular be suitable for use in the treatment of pain. This object has been achieved by the subject-matter of the patent claims. 3 GRA 4216-foreign filing It was surprisingly found that the compounds according to the invention are highly potent and selective inhibitors of the NaV1.8 channel. Further it was surprisingly found that the compounds according to the invention have ad- vantageous properties compared to the NaV1.8 inhibitors of the prior art. The invention relates to a compound according to general formula (I) wherein R1represents H or OH; A and B independently from one another represent phenyl, 5 to 10-membered heteroaryl, C3-7-cycloalkyl, or 4- to 10-membered heterocycloalkyl; R2 and R3 independently from one another represent F, Cl, CN, C1-4-alkyl, C3-6-cycloalkyl, NH2, N(H)C1-4-alkyl, N(C1-4-alkyl)2, OH, or O-C1-4-alkyl; x and y independently from one another represent 0, 1, 2, 3, or 4; R4 represents H, Cl, C1-6-alkyl, or C3-6-cycloalkyl; L represents bond, C1-3-alkylene or C1-2-alkylene-N(H); and R5represents S(=O)R6, S(=O)(=NH)R6, S(=O)(=N(C1-4-alkyl))R6, S(=O)(=NR6)R6, S(=O)2R6, S(=O)2NH2, S(=O)2N(H)R6, or S(=O)2N(C1-4-alkyl)R6; R6 represents C1-6-alkyl, C3-7-cycloalkyl, 4- to 10-membered heterocycloalkyl, C1-4-alkylene-(C3-7-cyclo- alkyl), or C1-4-alkylene-(4- to 7-membered heterocycloalkyl); or R4and R5together with the carbon atoms to which they are connected form 5- to 7- membered heterocycloalkyl; wherein C1-6-alkyl, C1-4-alkyl, C1-4-alkylene, C1-3-alkylene and C1-2-alkylene in each case independently from one another is linear or branched, saturated or unsaturated; wherein C1-6-alkyl, C1-4-alkyl, C1-4-alkylene, C1-3-alkylene, C1-2-alkylene, C3-6-cycloalkyl, C5-7-cycloalkyl, 4- to 7- membered heterocycloalkyl, 4- to 10- membered heterocycloalkyl, and 5- to 7- membered heterocycloalkyl in each case independently from one another are unsubstituted or mono- or polysubstituted with one or more substit- uents selected from F; Cl; CN; C1-6-alkyl; C1-6-alkylene-NH2, CF3; CF2H; CFH2; C(O)-C1-6-alkyl; C(O)-OH; C(O)- OC1-6-alkyl; C(O)-NH2; C(O)-N(H)(C1-6-alkyl); C(O)-N(C1-6-alkyl)2; OH; =O; OCF3; OCF2H; OCFH2; O-C1-6- alkyl;; NH2; N(H)(C1-6-alkyl); N(C1-6-alkyl)2; N(H)-C(O)-C1-6-alkyl; and S(O)2-C1-6-alkyl;; wherein phenyl, 5 to 10-membered heteroaryl and 5 or 6-membered heteroaryl in each case independently from one another are unsubstituted or mono- or polysubstituted with one or more substituents selected from F; Cl; CN; 4 GRA 4216-foreign filing C1-6-alkyl; CF3; CF2H; CFH2; OH; OCF3; OCF2H; OCFH2; O-C1-6-alkyl; NH2; N(H)(C1-6-alkyl); and N(C1-6-al- kyl)2; in the form of the free compound or a physiologically acceptable salt thereof. In a preferred embodiment, the compound according to the invention is present in form of the free compound. For the purpose of specification, "free compound" preferably means that the compound according to the invention is not present in form of a salt. Methods to determine whether a chemical substance is present as the free compound or as a salt are known to the skilled artisan such as14N or15N solid state NMR, x-ray diffraction, x-ray powder diffraction, IR, Raman, XPS.1H-NMR recorded in solution may also be used to consider the presence of protona- tion. In another preferred embodiment, the compound according to the invention is present in form of a physiologically acceptable salt. For the purposes of this specification, the term "physiologically acceptable salt" preferably refers to a salt obtained from a compound according to the invention and a physiologically acceptable acid or base. According to the invention, the compound according to the invention may be present in any possible form includ- ing solvates, cocrystals and polymorphs. For the purposes of this specification, the term "solvate" preferably refers to an adduct of (i) a compound according to the invention and / or a physiologically acceptable salt thereof with (ii) distinct molecular equivalents of one or more solvents. Further, the compound according to the invention may be present in form of the racemate, enantiomers, diastere- omers, tautomers or any mixtures thereof. The person skilled in the art knows that imidazoles show annular tau- tomerism. The compounds according to the invention may have one or more stereocenter. The person skilled in art knows by looking at a chemical structure whether the depicted compound has one or more stereocenters or not. For some compounds according to the invention that have one or more stereocenters and which chemical structures are disclosed in the examples of the present application, the chemical structure includes bold bonds and / or hashed bonds to indicate the relative structural orientation of those substituents connected by the bold bonds and / or hashed bonds to the superior structure. If the bold bonds and / or hashed bonds are depicted in form of a wedge, the absolute stereochemical configuration of the compound is known and thereby indicated. If the bold bonds and / or hashed bonds are depicted as a straight bond (i.e. no wedge), the absolute stereochemical configuration of the compound has not been determined. In that case, the bold bonds and / or hashed bonds merely serve to indicate that this par- ticular compound is present as one enantiomer or one diastereomer (e.g. cis-diastereomer (i.e. mixture of two cis- enantiomers) or trans-diastereomer (i.e. mixture of two trans-enantiomers)). All compounds according to the in- vention that have one or more stereocenters but which chemical structures disclosed in the examples of the present application do not include bold bonds and / or hashed bonds, are present as a mixture of the respective stereoiso- mers. The invention also includes isotopic isomers of a compound of the invention, wherein at least one atom of the compound is replaced by an isotope of the respective atom which is different from the naturally predominantly occurring isotope, as well as any mixtures of isotopic isomers of such a compound. Preferred isotopes are2H 5 GRA 4216-foreign filing (deuterium),3H (tritium),13C and14C. Isotopic isomers of a compound of the invention can generally be prepared by conventional procedures known to a person skilled in the art. According to the invention, the terms "C1-3-alkyl", ^C1-4-alkyl^ and ^C1-6-alkyl^ preferably mean acyclic and pref- erably saturated hydrocarbon residues, which can be linear (i.e. unbranched) or branched and which can be unsub- stituted or mono- or polysubstituted (e.g. di- or trisubstituted), and which contain 1 to 3 (i.e.1, 2, or 3), 1 to 4 (i.e. 1, 2, 3 or 4) or 1 to 6 (i.e.1, 2, 3, 4, 5 or 6) carbon atoms, respectively. Preferably, C1-3-alkyl, C1-4-alkyl and C1-6- alkyl are saturated. Preferred C1-3-alkyl groups are selected from the group consisting of methyl, ethyl, n-propyl, and 2-propyl. Preferred C1-4-alkyl groups are selected from the group consisting of methyl, ethyl, n-propyl, 2- propyl, n-butyl, isobutyl, sec-butyl and tert-butyl. Preferred C1-6-alkyl groups are selected from the group consist- ing of methyl, ethyl, n-propyl, 2-propyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 3-pentyl, 2- methylbutyl, 3-methylbutyl, 3-methylbut-2-yl, 2-methylbut-2-yl, 2,2-dimethylpropyl, and n-hexyl. Still further according to the invention, the terms ^C3-7-cycloalkyl^, ^C3-6-cycloalkyl^, and ^C5-7-cycloalkyl^ pref- erably means monocyclic or polycyclic, preferably monocyclic or bicyclic, aliphatic hydrocarbons containing 3 to 7 (i.e.3, 4, 5, 6 or 7), 3 to 6 (i.e.3, 4, 5 or 6) or 5 to 7 (i.e.5, 6 or 7) carbon atoms, wherein the hydrocarbons in each case can be saturated or unsaturated (but not aromatic), unsubstituted or mono- or polysubstituted. For the purpose of this specification, ^polycyclic^ and ^bicyclic^ shall preferably mean fused, bridged or spiro cyclic systems. Preferably, C3-7-cycloalkyl, C3-6-cycloalkyl, and C5-7-cycloalkyl are saturated. C3-7-cycloalkyl, C3-6-cycloalkyl, and C5-7-cycloalkyl can be bound to the respective superordinate general structure via any desired and possible ring member of the cycloalkyl group. C3-7-cycloalkyl, C3-6-cycloalkyl and C5-7-cycloalkyl can also be fused with further saturated or (partially) unsaturated heterocycloalkyl, aromatic or heteroaromatic ring systems, preferably aromatic ring system, which can in turn be unsubstituted or mono- or polysubstituted, thereby being part of a bi- or polycy- clic system having up to 14 ring members. Accordingly, the terms ^C3-7-cycloalkyl^, ^C3-6-cycloalkyl^, and ^C5-7- cycloalkyl^ preferably include monocyclic or polycyclic, preferably monocyclic or bicyclic, aliphatic hydrocar- bons containing 3 to 7, 3 to 6 or 5 to 7 carbon atoms; which are fused with a phenyl moiety. Preferred C3-7- cycloalkyl groups are selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cy- cloheptyl, spiro[2.2]pentyl, spiro[2.3]hexyl, spiro[3.3]heptyl, bicyclo[1.1.0]butyl, bicyclo[2.1.0]pentyl, bicy- clo[2.1.1]hexyl, bicyclo[3.1.1]heptyl, bicyclo[2.2.1]heptyl, bicyclo[3.1.0]hexyl, bicyclo[3.2.0]heptyl, and bicy- clo[4.1.0]heptyl. Preferred C3-6-cycloalkyl groups are selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, spiro[2.2]pentyl, spiro[2.3]hexyl, bicyclo[1.1.0]butyl, bicyclo[2.1.0]pentyl, bicyclo[2.1.1]hexyl, and bicyclo[3.1.0]hexyl. Preferred C5-7-cycloalkyl groups are selected from the group consisting of cyclopentyl, cyclohexyl, cycloheptyl, spiro[2.2]pentyl, spiro[2.3]hexyl, spiro[3.3]heptyl, bicyclo[2.1.0]pentyl, bicyclo[2.1.1]hexyl, bicyclo[3.1.1]hep- tyl, bicyclo[2.2.1]heptyl, bicyclo[3.1.0]hexyl, bicyclo[3.2.0]heptyl, and bicyclo[4.1.0]heptyl. Further according to the present invention, the terms ^C1-3-alkylene^ and ^C1-2-alkylene^ relate to linear or branched, preferably linear, and preferably saturated aliphatic residues which are preferably selected from the group consisting of methylene (-CH2-), ethylene (-CH2CH2-), propylene (-CH2CH2CH2- or ^C(CH3)2-), more pref- erably methylene (-CH2-) and ethylene (-CH2CH2). 6 GRA 4216-foreign filing According to the invention, C1-6-alkyl, C1-4-alkyl, C1-4-alkylene, C1-3-alkylene and C1-2-alkylene in each case inde- pendently from one another is linear or branched, saturated or unsaturated. In a preferred embodiment, C1-6-alkyl, C1-4-alkyl, C1-4-alkylene, C1-3-alkylene and C1-2-alkylene in each case independently from one another is linear or branched, and saturated. According to the present invention, the terms "4 to 7-membered heterocycloalkyl^, ^5 to 7-membered heterocy- cloalkyl^ and ^4 to 10-membered heterocycloalkyl^ preferably mean monocyclic or polycyclic, preferably mono- cyclic or bicyclic, heterocycloaliphatic saturated or unsaturated (but not aromatic) residues having 4 to 7 (i.e.4, 5, 6 or 7), 5 to 7 (i.e.5, 6 or 7) or 4 to 10 (i.e.4, 5, 6, 7, 8, 9 or 10) ring memberswherein in each case at least one, if appropriate also two or three carbon atoms are replaced by a heteroatom or a heteroatom group each selected independently of one another from the group consisting of O, S, S(=O), S(=O)2, N, NH and N(C1-4-alkyl) such as N(CH3), wherein the carbon atoms of the ring can be unsubstituted or mono- or polysubstituted. Preferably, 4 to 7-membered heterocycloalkyl, 5 to 7-membered heterocycloalkyl and 4 to 10-membered heterocycloalkyl are sat- urated. The 4 to 7-membered heterocycloalkyl, the 5 to 7-membered heterocycloalkyl and the 4 to 10-membered heterocycloalkyl groups can also be fused with further saturated or (partially) unsaturated cycloalkyl, aromatic or heteroaromatic ring systems, preferably aromatic ring system, which can in turn be unsubstituted or mono- or polysubstituted, if not indicated otherwise, thereby being being part of a bi- or polycyclic system having up to 14 ring members.. In a preferred embodiment, 4 to 7-membered heterocycloalkyl, 5 to 7-membered heterocycloalkyl and 4 to 10-membered heterocycloalkyl are not fused with further ring systems. Still more preferably, 4 to 7- membered heterocycloalkyl, 5 to 7-membered heterocycloalkyl and 4 to 10-membered heterocycloalkyl are not fused with further ring systems and are saturated. In another preferred embodiment, 4 to 7-membered heterocy- cloalkyl, 5 to 7-membered heterocycloalkyl and 4 to 10-membered heterocycloalkyl are condensed with further ring systems, preferably phenyl. The 4 to 7-membered heterocycloalkyl, the 5 to 7-membered heterocycloalkyl and 4 to 10-membered heterocycloalkyl group can be bound to the superordinate general structure via any desired and possible ring member of the heterocycloaliphatic residue if not indicated otherwise. In a preferred embodi- ment, 4 to 7-membered heterocycloalkyl, 5 to 7-membered heterocycloalkyl and 4 to 10-membered heterocyclo- alkyl are bound to the superordinate general structure via a carbon atom. In another preferred embodiment, 4 to 7- membered heterocycloalkyl, 5 to 7-membered heterocycloalkyl and 4 to 10-membered heterocycloalkyl are bound to the superordinate general structure via a heteroatom, in particular N. Preferred 4 to 7-membered heterocycloalkyl groups are selected from the group consisting of 1,1-dioxo tetrahy- drothiophenyl, 1-oxo thiomorpholinyl, tetrahydropyranyl, oxetanyl, tetrahydrofuranyl, morpholinyl, pyrrolidinyl, pyrrolidinonyl, azetidinyl, piperazinyl, piperazinonyl, piperidinyl, thietanyl, 1,1-dioxothietanyl, 2,6-dia- zaspiro[3.3]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, azepanyl, dioxepanyl, oxazepanyl, diazepanyl, thiazolidinyl, tetrahydrothiophenyl, tetrahydropyridinyl, thiomorpholinyl, 4-methylpiperazinyl, morpholinonyl, dithiolanyl, di- hydropyrrolyl, dioxanyl, dioxolanyl, dihydropyridinyl, dihydrofuranyl, dihydroisoxazolyl, dihydrooxazolyl, imid- azolidinyl, isoxazolidinyl, oxazolidinyl, pyrazolidinyl, and cromanyl. Particularly preferred 4 to 7-membered heterocycloalkyl groups are selected from 5 to 7-membered heterocyclo- alkyl groups. Preferred 5 to 7-membered heterocycloalkyl groups are selected from the group consisting of 1,1- dioxo tetrahydrothiophenyl, 1-oxo thiomorpholinyl, tetrahydropyranyl, tetrahydrofuranyl, morpholinyl, pyrroli- dinyl, pyrrolidinonyl, piperazinyl, piperazinonyl, piperidinyl, 2,6-diazaspiro[3.3]heptyl, 2,5-diazabicy- 7 GRA 4216-foreign filing clo[2.2.1]heptyl, azepanyl, dioxepanyl, oxazepanyl, diazepanyl, thiazolidinyl, tetrahydrothiophenyl, tetrahydro- pyridinyl, thiomorpholinyl, 4-methylpiperazinyl, morpholinonyl, dithiolanyl, dihydropyrrolyl, dioxanyl, dioxola- nyl, dihydropyridinyl, dihydrofuranyl, dihydroisoxazolyl, dihydrooxazolyl, imidazolidinyl, isoxazolidinyl, oxa- zolidinyl, pyrazolidinyl and cromanyl. Preferred 4 to 10-membered heterocycloalkyl groups are selected from the group consisting of tetrahydro-2H- thiopyranyl 1,1-dioxide, 1-oxo thiomorpholinyl, tetrahydropyranyl, oxetanyl, tetrahydrofuranyl, morpholinyl, pyr- rolidinyl, pyrrolidinonyl, azetidinyl, piperazinyl, piperazinonyl, piperidinyl, thietanyl, 1,1-dioxothietanyl, 2,6-di- azaspiro[3.3]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, cromanyl, thiepanyl 1,1-dioxide, 1,2-thiazepanyl 1,1-dioxide, 2,5,6,7-tetrahydro-1,2-thiazepinyl 1,1-dioxide, 5,6-dihydro-2H-1,2-thiazinyl 1,1-dioxide, 1,1-dioxo tetrahydrothi- ophenyl, 2-oxaspiro[3.4]octyl, 5-oxaspiro[2.4]heptyl, 2-oxabicyclo[2.1.1]hexyl, 1,1-dioxo thietanyl, 2,3-dihydro- [1,4]dioxino[2,3-b]pyridyl, tetrahydro-1,8-naphthyridinyl, azepanyl, dioxepanyl, oxazepanyl, diazepanyl, thiazol- idinyl, tetrahydrothiophenyl, tetrahydropyridinyl, thiomorpholinyl, 4-methylpiperazinyl, morpholinonyl, dithiola- nyl, dihydropyrrolyl, dioxanyl, dioxolanyl, dihydropyridinyl, dihydrofuranyl, dihydroisoxazolyl, dihydrooxazolyl, imidazolidinyl, isoxazolidinyl, oxazolidinyl, pyrazolidinyl, 5,7-dihydrofuro[3,4-b]pyridinyl, and 5,7-dihydro- furo[3,4-d]pyrimidinyl, more preferably tetrahydro-2H-thiopyranyl 1,1-dioxide, 1-oxo thiomorpholinyl, tetrahy- dropyranyl, oxetanyl, tetrahydrofuranyl, pyrrolidinyl, pyrrolidinonyl, azetidinyl, piperazinyl, piperazinonyl, piper- idinyl, 1,1-dioxothietanyl, 2,6-diazaspiro[3.3]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, cromanyl, thiepanyl 1,1-diox- ide, 1,2-thiazepanyl 1,1-dioxide, 2,5,6,7-tetrahydro-1,2-thiazepinyl 1,1-dioxide and 5,6-dihydro-2H-1,2-thiazinyl 1,1-dioxide. According to the present invention, the terms ^5 to 10-membered heteroaryl^ and "5- to 6-membered heteroaryl^ preferably mean a 5, 6, 7, 8, 9 or 10-membered and 5 or 6-membered monocyclic or bicyclic aromatic residue, respectively, which contains at least 1, if appropriate also 2, 3, 4 or 5 heteroatoms, wherein the heteroatoms are each selected independently of one another from the group S, N and O and the heteroaryl residue can be unsubsti- tuted or mono- or polysubstituted, if not indicated otherwise. In the case of substitution on the heteroaryl, the substituents can be the same or different and be in any desired and possible position of the heteroaryl. The binding to the superordinate general structure can be carried out via any desired and possible ring member of the heteroaryl residue if not indicated otherwise. Preferably, the 5 to 10-membered heteroaryl and 5- to 6-membered heteroaryl are bound to the suprordinate general structure via a carbon atom of the heterocycle. The heteroaryl can also be fused with further saturated or (partially) unsaturated cycloalkyl, or heterocycloalkyl ring systems, which can in turn be unsubstituted or mono- or polysubstituted, thereby being being part of a bi- or polycyclic system having up to 14 ring members.. In a preferred embodiment, the 5 to 10-membered heteroaryl and 5- to 6-membered het- eroaryl are not fused with further saturated or (partially) unsaturated cycloalkyl, or heterocycloalkyl ring systems. Preferably, the 5 to 10-membered heteroaryl is selected from 5- to 6-membered heteroaryl. Preferably, the 5- to 6- membered heteroaryl is selected from the group consisting of pyridyl (i.e.2-pyridyl, 3-pyridyl, 4-pyridyl), pyrim- idinyl, pyridazinyl, pyrazinyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, furanyl, thienyl (thiophenyl), triazolyl, thiadiazolyl, 4,5,6,7-tetrahydro-2H-indazolyl, 2,4,5,6-tetrahydrocyclopenta[c]pyra- zolyl, benzofuranyl, benzoimidazolyl, benzothienyl, benzothiadiazolyl, benzothiazolyl, benzotriazolyl, benzooxa- zolyl, benzooxadiazolyl, quinazolinyl, quinoxalinyl, carbazolyl, quinolinyl, dibenzofuranyl, dibenzothienyl, imid- azothiazolyl, indazolyl, indolizinyl, indolyl, isoquinolinyl, naphthyridinyl, oxazolyl, oxadiazolyl, phenazinyl, phe- nothiazinyl, phthalazinyl, purinyl, phenazinyl, tetrazolyl and triazinyl. Particularly preferred 5- to 6-membered heteroaryl are selected from the group consisting of pyridyl (i.e.2-pyridyl, 3-pyridyl, 4-pyridyl). 8 GRA 4216-foreign filing In connection with the terms ^C1-6-alkyl^, ^C1-4-alkyl^, ^C1-4-alkylene^, ^C1-3-alkylene^, ^C1-2-alkylene^, ^C3-7- cycloalkyl^, ^C3-6-cycloalkyl^, ^C5-7-cycloalkyl^, ^4- to 7- membered heterocycloalkyl^, ^4- to 10- membered heterocycloalkyl^ and ^5- to 7- membered heterocycloalkyl^ the term "substituted" refers in the sense of the in- vention, with respect to the corresponding residues or groups, to the single substitution (monosubstitution) or multiple substitution (polysubstitution), e.g. disubstitution, trisubstitution or tetrasubstitution; more preferably to monosubstitution, disubstitution or trisubstitution; of one or more hydrogen atoms each independently of one an- other by at least one substituent. In case of a multiple substitution, i.e. in case of polysubstituted residues, such as di- or trisubstituted residues, these residues may be polysubstituted either on different or on the same atoms, for example trisubstituted on the same carbon atom, as in the case of CF3, CH2CF3or disubstituted as in the case of 1,1-difluorocyclopropyl, or at various points, as in the case of 1-chloro-3-fluorocyclopropyl. The multiple substi- tution can be carried out using the same or using different substituents. If a residue occurs multiply within a molecule, then this residue can have respectively different meanings for various substituents: if, for example, both R4and R6denote C1-6-alkyl, then C1-6-alkyl can e.g. represent methyl for R4and can represent 2-propyl for R6. According to the invention, C1-6-alkyl, C1-4-alkyl, C1-4-alkylene, C1-3-alkylene, C1-2-alkylene, C3-7-cycloalkyl, C3- 6-cycloalkyl, C5-7-cycloalkyl, 4- to 7- membered heterocycloalkyl, 4- to 10- membered heterocycloalkyl and 5- to 7- membered heterocycloalkyl in each case independently from one another are unsubstituted or mono- or pol- ysubstituted with one or more substituents selected from F; Cl; CN; C1-6-alkyl; C1-6-alkylene-NH2, CF3; CF2H; CFH2; C(O)-C1-6-alkyl; C(O)-OH; C(O)-OC1-6-alkyl; C(O)-NH2; C(O)-N(H)(C1-6-alkyl); C(O)-N(C1-6-alkyl)2; OH; =O; OCF3; OCF2H; OCFH2; O-C1-6-alkyl;; NH2; N(H)(C1-6-alkyl); N(C1-6-alkyl)2; N(H)-C(O)-C1-6-alkyl; and S(O)2-C1-6-alkyl.. Further according to the invention, phenyl, 5 to 10-membered heteroaryl and 5 or 6-membered heteroaryl in each case independently from one another are unsubstituted or mono- or polysubstituted with one or more substituents selected from F; Cl; CN; C1-6-alkyl; CF3; CF2H; CFH2; OH; OCF3; OCF2H; OCFH2; O-C1-6-alkyl; NH2; N(H)(C1-6-alkyl); and N(C1-6-alkyl)2; preferably F; Cl; C1-6-alkyl; CF3; OH; OCF3; and O-C1-6-alkyl. According to the invention, A and B independently from one another represent phenyl, 5 to 10-membered het- eroaryl, C3-7-cycloalkyl, or 4- to 10-membered heterocycloalkyl; preferably phenyl, 5 or 6-membered heteroaryl, C3-7-cycloalkyl, or 4- to 7-membered heterocycloalkyl ; more preferably phenyl, 5- or 6-membered heteroaryl, or C3-7-cycloalkyl; more preferably phenyl or 5- or 6-membered heteroaryl. In a preferred embodiment, at least one of A and B represents phenyl or 5- or 6-membered heteroaryl. In another preferred embodiment, A represents phenyl. In still another preferred embodiment, B represents phenyl, 5- or 6-membered heteroaryl, or C3-7-cycloalkyl; more preferably phenyl or 5- or 6-membered heteroaryl; most preferably phenyl or pyridyl. In another preferred embodiment, B represents phenyl, pyridyl, thiophenyl, thiazolyl, oxazolyl, cyclobutyl, cyclo- pentyl, cyclohexyl, spiro[2.3]hexyl, spiro[3.3]heptyl or cromanyl. According to the invention, R1represents H, or OH. In a preferred embodiment, R1represents H. 9 GRA 4216-foreign filing According to the invention, R2and R3independently from one another represent F, Cl, CN, C1-4-alkyl, C3-6-cyclo- alkyl, NH2, N(H)C1-4-alkyl, N(C1-4-alkyl)2, OH, or O-C1-4-alkyl; preferably wherein C1-4-alkyl can in each case independently be unsubstituted, mono-, di- or trisubstituted with F. In a preferred embodiment, R2 represents F, Cl, OCH3, OCF3, or CHF2. In another preferred embodiment, R3represents F, Cl, NH2, C1-4-alkylor O-C1-4-alkyl; preferably wherein C1-4- alkyl can in each case independently be unsubstituted, mono-, di- or trisubstituted with F. Particularly preferably, R3 represents F, Cl, NH2, CH3, CF3, CHF2, OCH3, OCF3, OCHF2 or O-CH2-CF3. In a preferred embodiment, when x and y are 2, 3 or 4; the 2, 3 or 4 entities of R2 and the 2, 3 or 4 entities of R3 are not identical. In a particularly preferred embodiment, when x represents 2, one R2will represent F and one R2will represent Cl. In a particularly preferred embodiment, when y represents 2, one R3will represent F and one R3will represent Cl. According to the invention, x and y independently from one another represent 0, 1, 2, 3, or 4. In a preferred embodiment, x and y independently from one another represent 1 or 2. In another preferred embodiment, x and y independently from one another represent 0, 1, 2 or 3; more preferably 0, 1 or 2; most preferably 1 or 2 and inparticular 2. In another preferred embodiment, x and y independently from one another represent 1, 2, 3, or 4; preferably 1, 2 or 3; more preferably 1 or 2; and most preferably 2. According to the invention, R4represents H, Cl, C1-6-alkyl, or C3-6-cycloalkyl; preferably H, Cl, methyl, ethyl, CH2OH, CH2OCH3, CF3or cyclopropyl. In a preferred embodiment, R4represents H. According to the invention, L represents bond, C1-3-alkylene or C1-2-alkylene-N(H). In a preferred embodiment, L represents bond or C1-3-alkylene; more preferably bond, methylene, or ethylene. According to the invention, R5represents S(=O)R6, S(=O)(=NH)R6, S(=O)(=N(C1-4-alkyl))R6, S(=O)(=NR6)R6, S(=O)2R6, S(=O)2NH2, S(=O)2N(H)R6, or S(=O)2N(C1-4-alkyl)R6.. In a preferred embodiment, R5 represents S(=O)R6, S(=O)(=NH)R6, S(=O)(=N(C1-4-alkyl))R6, S(=O)2R6, S(=O)2NH2, S(=O)2N(H)R6, or S(=O)2N(C1-4-alkyl)R6. . According to the invention, R6 represents C1-6-alkyl, C3-7-cycloalkyl, 4- to 10-membered heterocycloalkyl, C1-4- alkylene-(C3-7-cycloalkyl), or C1-4-alkylene-(4- to 7-membered heterocycloalkyl). In a preferred embodiment, R6represents (i) C1-6-alkyl selected from the group consisting of methyl, ethyl, n-propyl, 2-propyl, n-butyl, isobutyl, sec- butyl, tert-butyl, n-pentyl, 2-pentyl, 3-pentyl, 2-methylbutyl, 3-methylbutyl, 3-methylbut-2-yl, 2-methyl- but-2-yl, 2,2-dimethylpropyl, and n-hexyl; 10 GRA 4216-foreign filing (ii) C3-7-cycloalkyl selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cy- cloheptyl, spiro[2.2]pentyl, spiro[2.3]hexyl, spiro[3.3]heptyl, bicyclo[1.1.0]butyl, bicyclo[2.1.0]pentyl, bi- cyclo[2.1.1]hexyl, bicyclo[3.1.1]heptyl, bicyclo[2.2.1]heptyl, bicyclo[3.1.0]hexyl, bicyclo[3.2.0]heptyl, and bicyclo[4.1.0]heptyl; (iii) 4- to 7-membered heterocycloalkyl selected from the group consisting of 1,1-dioxo tetrahydrothiophenyl, 1-oxo thiomorpholinyl, tetrahydropyranyl, oxetanyl, tetrahydrofuranyl, morpholinyl, pyrrolidinyl, pyrroli- dinonyl, azetidinyl, piperazinyl, piperazinonyl, piperidinyl, thietanyl, 1,1-dioxothietanyl, 2,6-dia- zaspiro[3.3]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, tetrahydro-2H-thiopyranyl 1,1-dioxide, azepanyl, diox- epanyl, oxazepanyl, diazepanyl, thiazolidinyl, tetrahydrothiophenyl, tetrahydropyridinyl, thiomorpholinyl, 4-methylpiperazinyl, morpholinonyl, dithiolanyl, dihydropyrrolyl, dioxanyl, dioxolanyl, dihydropyridinyl, dihydrofuranyl, dihydroisoxazolyl, dihydrooxazolyl, imidazolidinyl, isoxazolidinyl, oxazolidinyl, and py- razolidinyl; (iv) C1-4-alkylene-(C3-7-cycloalkyl) selected from the group consisting of (CH2)1-2-cyclopropyl, (CH2)1-2-cyclo- butyl, (CH2)1-2-cyclopentyl, (CH2)1-2-cyclohexyl; (CH2)1-2-cycloheptyl, (CH2)1-2-spiro[2.2]pentyl, (CH2)1-2- spiro[2.3]hexyl, (CH2)1-2-spiro[3.3]heptyl, (CH2)1-2-bicyclo[1.1.0]butyl, (CH2)1-2-bicyclo[2.1.0]pentyl, (CH2)1-2-bicyclo[2.1.1]hexyl, (CH2)1-2-bicyclo[3.1.1]heptyl, (CH2)1-2-bicyclo[2.2.1]heptyl, (CH2)1-2-bicy- clo[3.1.0]hexyl, (CH2)1-2-bicyclo[3.2.0]heptyl, and (CH2)1-2-bicyclo[4.1.0]heptyl; or (v) C1-4-alkylene-(4- to 7-membered heterocycloalkyl) selected from the group consisting of (CH2)1-2-(1,1-di- oxo tetrahydrothiophenyl), (CH2)1-2-(1-oxo thiomorpholinyl), (CH2)1-2-tetrahydropyranyl, (CH2)1-2-oxeta- nyl, (CH2)1-2-tetrahydrofuranyl, (CH2)1-2-morpholinyl, (CH2)1-2-pyrrolidinyl, (CH2)1-2-pyrrolidinonyl, (CH2)1-2-azetidinyl, (CH2)1-2-piperazinyl, (CH2)1-2-piperazinonyl, (CH2)1-2-piperidinyl, (CH2)1-2-thietanyl, (CH2)1-2-(1,1-dioxothietanyl), (CH2)1-2-(2,6-diazaspiro[3.3]heptyl), (CH2)1-2-(2,5-diazabicyclo[2.2.1]hep- tyl), (CH2)1-2-tetrahydro-2H-thiopyranyl 1,1-dioxide, (CH2)1-2-azepanyl, (CH2)1-2-dioxepanyl, (CH2)1-2-ox- azepanyl, (CH2)1-2-diazepanyl, (CH2)1-2-thiazolidinyl, (CH2)1-2-tetrahydrothiophenyl, (CH2)1-2-tetrahydro- pyridinyl, (CH2)1-2-thiomorpholinyl, (CH2)1-2-(4-methylpiperazinyl), (CH2)1-2-morpholinonyl, (CH2)1-2-di- thiolanyl, (CH2)1-2-dihydropyrrolyl, (CH2)1-2-dioxanyl, (CH2)1-2-dioxolanyl, (CH2)1-2-dihydropyridinyl, (CH2)1-2-dihydrofuranyl, (CH2)1-2-dihydroisoxazolyl, (CH2)1-2-dihydrooxazolyl, (CH2)1-2-imidazolidinyl, (CH2)1-2-isoxazolidinyl, (CH2)1-2-oxazolidinyl, and (CH2)1-2-pyrazolidin; wherein said methyl, ethyl, n-propyl, 2-propyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 3-pentyl, 2-methylbutyl, 3-methylbutyl, 3-methylbut-2-yl, 2-methylbut-2-yl, 2,2-dimethylpropyl, n-hexyl, cyclopropyl, cy- clobutyl, cyclopentyl, cyclohexyl, cycloheptyl, spiro[2.2]pentyl, spiro[2.3]hexyl, spiro[3.3]heptyl, bicy- clo[1.1.0]butyl, bicyclo[2.1.0]pentyl, bicyclo[2.1.1]hexyl, bicyclo[3.1.1]heptyl, bicyclo[2.2.1]heptyl, bicy- clo[3.1.0]hexyl, bicyclo[3.2.0]heptyl, and bicyclo[4.1.0]heptyl, 1,1-dioxo tetrahydrothiophenyl, 1-oxo thiomor- pholinyl, tetrahydropyranyl, oxetanyl, tetrahydrofuranyl, morpholinyl, pyrrolidinyl, pyrrolidinonyl, azetidinyl, pi- perazinyl, piperazinonyl, piperidinyl, thietanyl, 1,1-dioxothietanyl, 2,6-diazaspiro[3.3]heptyl, 2,5-diazabicy- clo[2.2.1]heptyl, tetrahydro-2H-thiopyranyl 1,1-dioxide, azepanyl, dioxepanyl, oxazepanyl, diazepanyl, thiazoli- dinyl, tetrahydrothiophenyl, tetrahydropyridinyl, thiomorpholinyl, 4-methylpiperazinyl, morpholinonyl, dithiola- nyl, dihydropyrrolyl, dioxanyl, dioxolanyl, dihydropyridinyl, dihydrofuranyl, dihydroisoxazolyl, dihydrooxazolyl, imidazolidinyl, isoxazolidinyl, oxazolidinyl, and pyrazolidinyl in each case independently from one another are unsubstituted or mono- or polysubstituted with one or more substituents selected from F; Cl; CN; C1-6-alkyl; CF3; 11 GRA 4216-foreign filing CF2H; CFH2; C(O)-C1-6-alkyl; C(O)-OH; C(O)-OC1-6-alkyl; C(O)-NH2; C(O)-N(H)(C1-6-alkyl); C(O)-N(C1-6-al- kyl)2; OH; =O; OCF3; OCF2H; OCFH2; O-C1-6-alkyl;; NH2; N(H)(C1-6-alkyl); N(C1-6-alkyl)2; N(H)-C(O)-C1-6-al- kyl; and S(O)2-C1-6-alkyl. According to the invention, R4 and R5 can together with the carbon atoms to which they are connected form 5- to 7- membered heterocycloalkyl. In a preferred embodiment, R4and R5together with the carbon atoms to which they are connected form thiepanyl 1,1-dioxide, 1,2-thiazepanyl 1,1-dioxide, 2,5,6,7-tetrahydro-1,2-thiazepinyl 1,1-dioxide, or 5,6-dihydro-2H-1,2- thiazinyl 1,1-dioxide,, preferably wherein the thiepanyl 1,1-dioxide, 1,2-thiazepanyl 1,1-dioxide, 2,5,6,7-tetrahy- dro-1,2-thiazepinyl 1,1-dioxide, or 5,6-dihydro-2H-1,2-thiazinyl 1,1-dioxide, can be unsubstituted or monosubsti- tuted with CH3, F, Cl, OH, CF3, or OCH3; more preferably CH3,. In another preferred embodiment, R4 and R5 do not form together with the carbon atoms to which they are con- nected 5- to 7- membered heterocycloalkyl. According to the present invention, the compound according to the invention is preferably selected from the group consisting of 1 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(methylsulfonyl)-1H-imidazole 2 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(ethylsulfonyl)-1H-imidazole 3 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(cyclopropylsulfonyl)-1H-imidazole 4 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-(isopropylsulfonyl)-1H-imidazole 5 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-((tetrahydrofuran-3-yl)sulfonyl)-1H-imidazole 6 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-((tetrahydro-2H-pyran-4-yl)sulfonyl)-1H-imidazole 7 2-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-4-yl)sulfonyl)ethan-1-amine 8 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-chloro-4-(methylsulfonyl)-1H-imidazole 9 2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole-5-sulfonamide 10 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-methyl-1H-imidazole-5-sulfonamide 11 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(1-(dimethylamino)propan-2-yl)-1H-imidazole-5- sulfonamide 12 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2-(pyrrolidin-1-yl)ethyl)-1H-imidazole-5-sulfona- mide 13 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-4-isopropylpiperazine 14 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-4-ethylpiperazine 15 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-4-(methylsul- fonyl)piperazine 16 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2-hydroxyethyl)-N-methyl-1H-imidazole-5-sulfo- namide 17 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2-methoxyethyl)-1H-imidazole-5-sulfonamide 18 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2-(dimethylamino)ethyl)-1H-imidazole-5-sulfona- mide 19 1-(4-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)piperazin-1- yl)ethan-1-one 12 GRA 4216-foreign filing 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2-hydroxypropyl)-1H-imidazole-5-sulfonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(oxetan-2-ylmethyl)-1H-imidazole-5-sulfonamide 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-N,N-dimethylazeti- din-3-amine 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-N,N-dimethylpyrroli- din-3-amine 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2-(methylsulfonyl)ethyl)-1H-imidazole-5-sulfona- mide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2-hydroxyethyl)-1H-imidazole-5-sulfonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2-hydroxy-2-methylpropyl)-1H-imidazole-5-sul- fonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(1-methoxypropan-2-yl)-1H-imidazole-5-sulfona- mide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-methyl-N-(2-(methylsulfonyl)ethyl)-1H-imidazole- 5-sulfonamide 4-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)thiomorpholine 1- oxide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(3-methoxypropyl)-1H-imidazole-5-sulfonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(oxetan-3-ylmethyl)-1H-imidazole-5-sulfonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(3-(dimethylamino)propyl)-1H-imidazole-5-sulfo- namide 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-N,N-dimethylpiperi- din-4-amine ethyl ((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)glycinate 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(1,1-dioxidothietan-3-yl)-1H-imidazole-5-sulfona- mide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-((3R,4R)-4-hydroxytetrahydro-2H-pyran-3-yl)-1H- imidazole-5-sulfonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-N-methyl- 1H-imidazole-5-sulfonamide 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)azetidin-3-ol 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2,3-dimethoxypropyl)-1H-imidazole-5-sulfona- mide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(oxetan-3-yl)-1H-imidazole-5-sulfonamide 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)piperazine N-(2-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole)-5-sulfonamido)ethyl)acetamide N-(1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)azetidin-3-yl)aceta- mide 2-((2-(bis(3-chloro-4-fluorophenyl)methyl)-N-methyl-1H-imidazole)-5-sulfonamido)-N-me- thylacetamide 13 GRA 4216-foreign filing 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(3-methoxycyclobutyl)-1H-imidazole-5-sulfona- mide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(3-hydroxycyclopentyl)-1H-imidazole-5-sulfona- mide N-(1-acetylpiperidin-4-yl)-2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole-5-sulfona- mide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2,2-difluoroethyl)-1H-imidazole-5-sulfonamide 3-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole)-5-sulfonamido)-2,2-dimethylpro- panamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(1-methylpiperidin-4-yl)-1H-imidazole-5-sulfona- mide methyl ((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)glycinate 2-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole)-5-sulfonamido)propanamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(cyanomethyl)-1H-imidazole-5-sulfonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-methyl-N-(2-(methylamino)ethyl)-1H-imidazole-5- sulfonamide 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-3-methylpiperazine 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-N-methylpyrrolidin- 3-amine 2-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-2,6-dia- zaspiro[3.3]heptane 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(piperidin-3-yl)-1H-imidazole-5-sulfonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(methylsulfinyl)-1H-imidazole 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-methyl-5-(methylsulfinyl)-1H-imidazole (2-(bis(3-chloro-4-fluorophenyl)methyl)-4-methyl-1H-imidazol-5-yl)(imino)(methyl)-l6-sul- fanone 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-methyl-5-(methylsulfonyl)-1H-imidazole 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-cyclopropyl-5-(methylsulfonyl)-1H-imidazole 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(methylsulfonyl)-4-(trifluoromethyl)-1H-imidazole (2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)(imino)(methyl)-l6-sulfanone (2-(bis(3-chloro-4-fluorophenyl)methyl)-4-(methylsulfonyl)-1H-imidazol-5-yl)methanol 5-((3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-1H-imidazol-2-yl)methyl)-2-(2,2,2-trifluoro- ethoxy)pyridine 2-((3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-1H-imidazol-2-yl)methyl)-4-fluoroaniline 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-((methylsulfonyl)methyl)-1H-imidazole 2-((3-chloro-4-fluorophenyl)(4-(trifluoromethyl)cyclohexyl)methyl)-4-(methylsulfonyl)-1H- imidazole 3-chloro-6-((4-chlorophenyl)(4-(methylsulfonyl)-1H-imidazol-2-yl)methyl)-2-(trifluorome- thyl)pyridine 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-N-cyclopropyl-1H-imidazole-4-sul- fonamide 14 GRA 4216-foreign filing 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-4-(pyrrolidin-1-ylsulfonyl)-1H- imidazole 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-4-((3,3-difluoropyrrolidin-1-yl)sul- fonyl)-1H-imidazole 4-((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazol-4-yl)sul- fonyl)piperazin-2-one 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-N,N-dimethyl-1H-imidazole-4-sul- fonamide 1-((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazol-4-yl)sulfonyl)-4- methylpiperazine 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-N-(tetrahydrofuran-3-yl)-1H-imida- zole-4-sulfonamide 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-N-(3-hydroxycyclopentyl)-1H- imidazole-4-sulfonamide 2-((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazole)-4-sulfona- mido)acetamide 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-4-((3-methoxy-3-methylpyrrolidin- 1-yl)sulfonyl)-1H-imidazole 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-N-(2-methoxypropyl)-1H-imida- zole-4-sulfonamide 4-(azetidin-3-ylsulfonyl)-2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imida- zole 2-((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazole)-4-sulfona- mido)propanamide 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-4-((1-methylazetidin-3-yl)sulfonyl)- 1H-imidazole ((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazol-4-yl)sulfonyl)glycine 2-((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-N-methyl-1H-imidazole)-4-sul- fonamido)acetamide 2-((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazol-4-yl)sulfonyl)-2,5- diazabicyclo[2.2.1]heptane 1-((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazol-4-yl)sulfonyl)pipe- ridin-3-amine (1-((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazol-4-yl)sulfonyl)aze- tidin-3-yl)methanamine 4-((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazol-4-yl)sulfonyl)pipe- ridine 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-4-(pyrrolidin-3-ylsulfonyl)-1H- imidazole 4-((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazol-4-yl)sulfonyl)-1- methylpiperidine 15 GRA 4216-foreign filing 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-4-((1-methylpyrrolidin-3-yl)sul- fonyl)-1H-imidazole 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-N-(pyrrolidin-3-yl)-1H-imidazole-4- sulfonamide N-(azetidin-3-yl)-2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazole-4- sulfonamide N-(azetidin-3-ylmethyl)-2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imida- zole-4-sulfonamide 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-N-(2-hydroxycyclopentyl)-1H- imidazole-4-sulfonamide 1-((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazol-4-yl)sulfonyl)-3,5- dimethylpiperazine 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-N-(pyrrolidin-3-ylmethyl)-1H- imidazole-4-sulfonamide 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-N-(2-(dimethylamino)ethyl)-5-me- thyl-1H-imidazole-4-sulfonamide N-(3-aminocyclobutyl)-2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imida- zole-4-sulfonamide 2-(((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-4-yl)(methyl)(oxo)-l6-sulfaneyli- dene)amino)acetamide 2-amino-N-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-4-yl)(methyl)(oxo)-l6-sul- faneylidene)acetamide 2-((3-chloro-4-fluorophenyl)(5-chlorothiophen-2-yl)methyl)-5-methyl-4-(methylsulfonyl)-1H- imidazole 2-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-1H-imidazol-2-yl)methyl)-5-(trif- luoromethyl)thiazole 2-((3-chloro-4-fluorophenyl)(3,3-difluorocyclopentyl)methyl)-5-methyl-4-(methylsulfonyl)- 1H-imidazole azetidin-3-yl(2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)(imino)-l6-sulfanone (2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)(imino)(1-methylazetidin-3-yl)-l6- sulfanone 2-((4-chloro-3-fluorophenyl)(chroman-3-yl)methyl)-4-methyl-5-(methylsulfonyl)-1H-imida- zole 2-((3-chloro-4-fluorophenyl)(3,3-dimethylcyclobutyl)methyl)-5-methyl-4-(methylsulfonyl)- 1H-imidazole 2-((3-chloro-4-fluorophenyl)(6,6-difluorospiro[3.3]heptan-2-yl)methyl)-5-methyl-4-(methyl- sulfonyl)-1H-imidazole 2-((3-chloro-4-fluorophenyl)(3-(difluoromethoxy)cyclobutyl)methyl)-5-methyl-4-(methylsul- fonyl)-1H-imidazole 2-((3-chloro-4-fluorophenyl)(spiro[2.3]hexan-5-yl)methyl)-5-methyl-4-(methylsulfonyl)-1H- imidazole 16 GRA 4216-foreign filing (2-(bis(3-chloro-2,4-difluorophenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6- sulfanone (2-(bis(3-chloro-4,5-difluorophenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6- sulfanone (2-(bis(5-chloro-2,4-difluorophenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6- sulfanone (2-(bis(4-chloro-2-fluorophenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6-sul- fanone (2-(bis(2-chloro-4-fluorophenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6-sul- fanone (2-(bis(4-(trifluoromethoxy)phenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6- sulfanone (2-(bis(3-(trifluoromethoxy)phenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6- sulfanone (2-(bis(3-fluoro-4-(trifluoromethoxy)phenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(me- thyl)-l6-sulfanone 2-((2-(bis(3-chloro-4-fluorophenyl)methyl)-N-methyl-1H-imidazole)-5-sulfonamido)aceta- mide 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-3-methylpiperazine 2-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-2,5-dia- zabicyclo[2.2.1]heptane 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)piperidin-3-amine (1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)azetidin-3-yl)metha- namine ((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)glycine 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(4-hydroxytetrahydrofuran-3-yl)-1H-imidazole-5- sulfonamide 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-3,5-dimethylpipera- zine N-(azetidin-3-ylmethyl)-2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole-5-sulfonamide 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-2-methylpiperazine 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(pyrrolidin-3-yl)-1H-imidazole-5-sulfonamide N-(azetidin-3-yl)-2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole-5-sulfonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(pyrrolidin-3-ylmethyl)-1H-imidazole-5-sulfona- mide N-(3-aminocyclobutyl)-2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole-5-sulfonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(1-hydroxy-2-methylpropan-2-yl)-1H-imidazole-5- sulfonamide N-(3-aminocyclopentyl)-2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole-5-sulfonamide 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-N-methylazetidin-3- amine 17 GRA 4216-foreign filing 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(3-(methylamino)propyl)-1H-imidazole-5-sulfona- mide N-(3-aminopropyl)-2-(bis(3-chloro-4-fluorophenyl)methyl)-N-methyl-1H-imidazole-5-sulfo- namide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2-(methylamino)ethyl)-1H-imidazole-5-sulfona- mide 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)piperidin-4-amine 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2-methoxypropyl)-1H-imidazole-5-sulfonamide N-(2-amino-2-methylpropyl)-2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole-5-sulfo- namide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N,N-dimethyl-1H-imidazole-5-sulfonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-cyclopropyl-1H-imidazole-5-sulfonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(pyrrolidin-1-ylsulfonyl)-1H-imidazole 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-((3,3-difluoropyrrolidin-1-yl)sulfonyl)-1H-imida- zole 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-((3-methoxy-3-methylpyrrolidin-1-yl)sulfonyl)-1H- imidazole 4-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)piperazin-2-one 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(5-oxopyrrolidin-3-yl)-1H-imidazole-5-sulfona- mide 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)pyrrolidin-3-ol 2-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole)-5-sulfonamido)acetamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(tetrahydrofuran-3-yl)-1H-imidazole-5-sulfona- mide 4-(azetidin-3-ylsulfonyl)-2-[bis(3-chloro-4-fluorophenyl)methyl]-1H-imidazole 2-[bis(3-chloro-4-fluorophenyl)methyl]-4-(1-methylazetidin-3-yl)sulfonyl-1H-imidazole 4-[[2-[bis(3-chloro-4-fluorophenyl)methyl]-1H-imidazol-4-yl]sulfonyl]piperidine 2-[bis(3-chloro-4-fluorophenyl)methyl]-4-pyrrolidin-3-ylsulfonyl-1H-imidazole (2-(bis(3-(difluoromethyl)-4-fluorophenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(me- thyl)-l6-sulfanone (2-(bis(4-chloro-2-methoxyphenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6- sulfanone (2-(bis(4-chloro-3-fluorophenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6-sul- fanone (2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(methyl-d3)-1H-imidazol-4-yl)(imino)(methyl)-l6- sulfanone (2-(bis(3-chloro-4-fluorophenyl)methyl)-5-cyclopropyl-1H-imidazol-4-yl)(imino)(methyl)-l6- sulfanone (2-(bis(3-chloro-4-fluorophenyl)methyl)-5-ethyl-1H-imidazol-4-yl)(imino)(methyl)-l6-sul- fanone 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-chloro-1H-imidazole-4-sulfonamide 18 GRA 4216-foreign filing 192 (2-(bis(3-chloro-4-fluorophenyl)methyl)-5-chloro-1H-imidazol-4-yl)(imino)(methyl)-l6-sul- fanone 193 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(methoxymethyl)-4-(methylsulfonyl)-1H-imidazole 194 6-(bis(3-chloro-4-fluorophenyl)methyl)-4-methyl-2,5-dihydroimidazo[4,5-e][1,2]thiazine 1,1- dioxide 195 7-(bis(3-chloro-4-fluorophenyl)methyl)-3,6-dihydro-2H-imidazo[4,5-f][1,2]thiazepine 1,1-di- oxide 196 7-(bis(3-chloro-4-fluorophenyl)methyl)-3,4,5,6-tetrahydro-2H-imidazo[4,5-f][1,2]thiazepine 1,1-dioxide 197 2-(bis(3-chloro-4-fluorophenyl)methyl)-5,6,7,8-tetrahydro-1H-thiepino[2,3-d]imidazole 4,4- dioxide 198 N-((2-(bis(3-chloro-4-fluorophenyl)methyl)-4-methyl-1H-imidazol-5-yl)methyl)methanesul- fonamide 199 3-chloro-6-((4-chlorophenyl)(4-(methylsulfonyl)-1H-imidazol-2-yl)methyl)-2-(trifluorome- thyl)pyridine 200 (2-((5-chloro-6-(trifluoromethyl)pyridin-2-yl)(4-chlorophenyl)methyl)-1H-imidazol-4- yl)(imino)(methyl)-l6-sulfanone 201 (3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-1H-imidazol-2-yl)(6-(2,2,2-trifluoroethoxy)py- ridin-3-yl)methanol 202 (2-((3-chloro-4-fluorophenyl)(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methyl)-1H-imidazol-4- yl)(imino)(methyl)-l6-sulfanone 203 (2-((3-chloro-4-fluorophenyl)(5-chloro-6-(trifluoromethyl)pyridin-3-yl)methyl)-1H-imidazol- 4-yl)(imino)(methyl)-l6-sulfanone 204 (3-chloro-4-fluorophenyl)(3,3-difluorocyclopentyl)(4-methyl-5-(methylsulfonyl)-1H-imida- zol-2-yl)methanol 205 5-((3-chloro-4-fluorophenyl)(4-methyl-5-(methylsulfonyl)-1H-imidazol-2-yl)methyl)-4-me- thyloxazol-2-amine in the form of the free compound or a physiologically acceptable salt thereof. In a preferred embodiment, the compound according to the invention is an inhibitor of NaV1.8. In the sense of the invention, the term "inhibitor of NaV1.8" preferably means that the respective compound exhibits in a patch clampassay an IC50 value on NaV1.8 of at most 10 µM (1010-6 mol / L); more preferably at most 1 µM; still morepreferably at most 500 nM (10-9mol / L); even more preferably at most 100 nM; and most preferably at most 10 nM. A preferred assay for testing compounds for their potency and method for determining an IC50 on NaV1.8 is described in the experimental part down below. In a preferred embodiment, the compound according to the invention is a selective inhibitor of NaV1.8. In the sense of the invention, the term "selective inhibitor of NaV1.8" preferably means that the respective compound preferably does not exhibit any inhibitory activity on NaV1.1, NaV1.2, NaV1.4, NaV1.5 and NaV1.6. The skilled artisan knows 19 GRA 4216-foreign filing suitable ways to determine whether a compound exhibits inhibitory effects on any of NaV1.1, NaV1.2, NaV1.4, NaV1.5 and NaV1.6. The invention therefore relates to a compound according to the invention for use in the inhibition of NaV1.8. Therefore, another aspect of the invention relates to a compound according to the invention for use in the treatment of pain. Still another aspect of the invention relates to a method of treatment of pain; comprising the administration of a therapeutically effective amount of a compound according to the invention to a subject in need thereof, pref- erably a human. A further aspect of the invention relates to a compound according to the invention as medicament. Another aspect of the invention relates to a pharmaceutical dosage form comprising a compound according to the invention. Preferably, the pharmaceutical dosage form comprises a compound according to the invention and one or more pharmaceutical excipients such as physiologically acceptable carriers, additives and / or auxiliary sub- stances; and optionally one or more further pharmacologically active ingredient. Examples of suitable physiolog- ically acceptable carriers, additives and / or auxiliary substances are fillers, solvents, diluents, colorings and / or bind- ers. These substances are known to the person skilled in the art (see H. P. Fiedler, Lexikon der Hilfsstoffe fur Pharmazie, Kosmetik und angrenzende Gebiete, Editio Cantor Aulendoff). The pharmaceutical dosage form according to the invention is preferably for systemic, topical or local administra- tion, preferably for oral administration. Therefore, the pharmaceutical dosage form can be in form of a liquid, semisolid or solid, e.g. in the form of injection solutions, drops, juices, syrups, sprays, suspensions, tablets, patches, films, capsules, plasters, suppositories, ointments, creams, lotions, gels, emulsions, aerosols or in multiparticulate form, for example in the form of pellets or granules, if appropriate pressed into tablets, decanted in capsules or suspended in a liquid, and can also be administered as such. The pharmaceutical dosage form according to the invention is preferably prepared with the aid of conventional means, devices, methods and processes known in the art. The amount of the compound according to the invention to be administered to the patient may vary and is e.g. dependent on the patient's weight or age and also on the type of administration, the indication and the severity of the disorder. Preferably 0.001 to 100 mg / kg, more preferably 0.05 to 75 mg / kg, most preferably 0.05 to 50 mg of a compound according to the invention are administered per kg of the patient's body weight. Therefore, another aspect of the invention relates to the pharmaceutical dosage form according to the invention for use in the treatment of pain. Still another aspect of the invention relates to a method of treatment of pain; compris- ing the administration of a pharmaceutical dosage form according to the invention to a subject in need thereof, preferably a human. General synthesis schemes Examples of the invention can be synthesized preferentially according to the general synthetic schemes below or using chemistry known to the person skilled in the art. As illustrated in Scheme 1, compounds of the general formula (A) can be treated with metal-organic compounds of the general formula (B) (wherein A=B, R2=R3and x=y) to afford compounds of general formula (C). Preferred metal-organic compounds include Grignard and organolithium reagents. Compounds of the general formula (C) can be converted into compounds of the general formula (D) with reactions known to the person skilled in the art. 20 GRA 4216-foreign filing Preferred transformations include reductions to get compounds of the general formula (D) with R1=H (preferred reagents include tin (II)chloride in acetic media). Scheme 1: A, B, R2, R3, R4, x and y are as defined in claim 1. As illustrated in Scheme 2, compounds of the general formula (D) can be halogenated, preferentially iodinated using I2to obtain compounds of the general formula (E). These compounds can be used to install a variety of L- R5moieties to yield compounds of the general formula (F1). One step procedures include the formation of sulfones using sulfinate salts (Synthesis, 2016, 48, 1939^1973). Multi step procedures include thioether formation undertransition metal catalysis followed by oxidation to yield sulfoxides (Chem. Rev. 2022, 122, 16110^16293) or sul-foximines (Chem. Eur. J. 2021, 27, 17293^17321). The obtained thioethers can also be converted into the corre-sponding sulfonylchlorides via oxidation (preferred reagents include DCDMH) and then further into sulfonamides upon treatment with nitrogen nucleophiles. In the case of R4=H, iodination using NIS yields bis-iodinated products (hal=I, R4=I) that are transformed into compounds of the general formula (E) with R4=H upon treatment with sodium thiosulfate. Scheme 2: A, B, R2, R3, R4, R5, L, x and y are as defined in claim 1. Hal=I, Br, Cl. As illustrated in Scheme 3, compounds of the general formula (G) can be added to aldehydes of the general formula (H) after deprotonation (preferred bases include LDA) to yield alcohols of the general formula (U). These com- pounds can be used to install a variety of L-R5moieties as described for the transformation (E) to (F) in scheme 2 to yield compounds of the general formula (J). Suitable protecting groups are known in the literature and include e.g. SEM (T. W. Green, P. G. M. Wuts, Protective Groups in Organic Synthesis, Wiley-Interscience, 2007, 4thedition, 872-893). Scheme 3: A, B, R2, R3, R4, R5, L, x and y are as defined in claim 1. PG=protecting group. 21 GRA 4216-foreign filing R5L N 2)x As illustrated in Scheme 4, compounds of the general formula (J) can be converted into compounds of the general formula (K) under formation of a new C-C bond. This transformation can optionally be preceded by deprotection (T. W. Green, P. G. M. Wuts, Protective Groups in Organic Synthesis, Wiley-Interscience, 2007, 4thedition, 872- 893) and / or transformation of the alcohol into a suitable leaving group. Preferred methods of construction of the new C-C bond include acid-catalyzed Friedel-Crafts type reactions (e.g using pTSA / anilines). Compounds of the general formula (J) can also be formed in situ (example 205) and converted into a carbamate leaving group in step. Friedel-Crafts type reactions (e.g using BF3 / TFA and appropriate nucleophiles) can be carried out with these car- bamates. Compounds of the general formula (J) can also be converted into compounds of the general formula (L) via a two-step sequence including first oxidation of the alcohol to a ketone (preferred oxidants include PCC) fol- lowed by addition of metal-organic compounds of the general formula (B). Compounds of the general formula (L) can be transformed into compounds of the general formula (F) using chemistry described for the transformation of (C) to (D) followed or preceded by deprotection (T. W. Green, P. G. M. Wuts, Protective Groups in Organic Synthesis, Wiley-Interscience, 2007, 4thedition, 872-893). For the transformations in scheme 4 the corresponding carbon-nucleophiles for the transformations (J) to (K) and (J) to (L) have to be chosen orthogonally, e.g. if a compound of the general formula (I) with the substituent B(R3)yis used, the chosen carbon nucleophile will attach A(R2)x and vice versa. Scheme 4: A, B, R2, R3, R4, R5, L, x and y are as defined in claim 1. PG=protecting group. As illustrated in Scheme 5, compounds of the general formula (F2) with R4=H can be converted into compounds of the general formula (M) using halogenation reactions, preferrable iodination using NIS. This halogen handle can be used to introduce a variety of different kinds of R4, e.g. alkyl substituents via Suzuki-type transition metal-catalyzed cross couplings (Chem. Soc. Rev. 2014, 43, 412-443) to give compounds of the general formula (F3).Introduction of R4 can also be carried out in multiple steps using standard functional group interconversions to build compounds with R5 / R4 being connected as exemplified for examples 83-85. Scheme 5: A, B, R1, R2, R3, R4, R5, L, x and y are as defined in claim 1. 22 GRA 4216-foreign filing As illustrated in Scheme 6, ketones of the general formula (N) can be converted into compounds of the general formula (O) using compounds of the general structure (G) after deprotonation (preferred bases include LDA). Compounds of the general formula (O) can be converted into compound of the genera formula (F) using the trans- formations described for the conversion of (E) to (F) and (C) to (D) and deprotection (T. W. Green, P. G. M. Wuts, Protective Groups in Organic Synthesis, Wiley-Interscience, 2007, 4thedition, 872-893). Scheme 6: A, B, R2, R3, R4, R5, L, x and y are as defined in claim 1. As illustrated in Scheme 7, compounds of the general formula (P) or (Q) can be converted into ketones of the general formula (R) or (S) using compounds of the general structure (V) after deprotonation (preferred bases in- clude LDA). Preferred leaving groups on compounds (P) or (Q) include N-methoxy-N-methyl or chloride. Ketones of the general formula (R) or (S) can be transformed into compounds of the general formula (T) using metal- organic compounds of the general formula (B). Compounds of the general formula (T) can be converted into final compounds using reactions described for the conversion of (C) to (D) and / or (E) to (F). Deprotection as indicated in scheme 7 is known in the art (T. W. Green, P. G. M. Wuts, Protective Groups in Organic Synthesis, Wiley- Interscience, 2007, 4thedition, 872-893). Synthesis of compounds of the general formula (P) or (Q) is known in the art. Scheme 7: A, B, R2, R3, R4, R5, L, x and y are as defined in claim 1. PG= protecting group, LG= leaving group. 23 GRA 4216-foreign filing List of abbreviations ACN= acetonitrile, ABPR= automated back pressure regulator, Boc= tert-butyloxycarbonyl, DAST= diethyla- minosulfur trifluoride, dba= dibenzylideneacetone, DBU= 1,8-diazabicyclo[5.4.0]undec-7-ene, DCDMH= 1,3-di- chlor-5,5-dimethylhydantoin, DCM= dichloromethane, DIBAL-H= diisobutylaluminium hydride, DIPA= diiso- propylamine, DIPEA= N,N-diisopropylethylamine, DMA= dimethylacetamide, DMF= dimethylformamide,DMSO= dimethyl sulfoxide, DPPA= diphenylphosphoryl azide, dppf= 1,1 -bis(diphenylphosphino)ferrocene,EA=ethyl acetate, FGI=functional group interconversion, Grubbs catalyst, 2nd generation= (1,3-bis(2,4,6-trime- thylphenyl)-2-imidazolidinylidene)dichlor(phenylmethylen)(tricyclohexylphosphan)ruthenium, HATU= [O-(7-Azabenzotriazol-1-yl)-N,N,N ,N -tetramethyluronium-hexafluorphosphat, Hex= hexane / hexanes , HPLC= high-performance liquid chromatography, LCMS= liquid chromatography^mass spectrometry, LDA= lithium diiso- propylamide, mCPBA= meta-chloroperoxybenzoic acid, Ms= mesyl, NCS= N-chlorosuccinimide, NIS= N- iodosuccinimide, NMO= N-methylmorpholine N-oxide, NMP= N-methyl-2-pyrrolidone, NMR= nuclear mag- netic resonance, PCC= pyridinium chlorochromate, pet ether=petroleum ether, PG=protecting group, pTSA= p- toluenesulfonic acid , Rt=retention time, RVC= reticulated vitreous carbon, SEM= 2-(trimethylsilyl)ethoxyme- thyl, SFC= supercritical fluid chromatography, T3P= propanephosphonic acid anhydride, TEA= triethylamine, TFA= trifluoroacetic acid, THF=tetrahydrofurane, TMS= trimethylsilyl, Xantphos= (9,9-dimethyl-9H-xanthene- 4,5-diyl)bis(diphenylphosphane). Intermediate 1 bis (1H-imidazol-2-yl)methanol 24 GRA 4216-foreign filing Mg (0.86 g, 35.71 mmol) was weighted in into a two-neck flask equipped with a reflux condenser and dried under an argon atmosphere. Then THF (7.0 mL), 4-bromo-2-chloro-1-fluorobenzene (7.5 g, 35.71 mmol) and DIBAL (1M in toluene, 0.4 mL) were added to the mixture sequentially at rt. The mixture was stirred at rt for 1 h. To the freshly prepared reagent was then added a solution of ethyl 1H-imidazole-2-carboxylate (1.0 g, 7.14 mmol) in THF (33.0 mL) at 0 °C and the reaction mixture was heated to 80 °C for 3 h. The reaction mixture was cooled to rt, quenched with ammonium chloride solution and extracted with ethyl acetate (3 x 100 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure to get the crude product which purified by CombiFlash column chromatography (SiO2, 0-60% EtOAc / Hex) to yield the title compound (1.5 g, 59%), LCMS: m / z [M+H]+= 355. Intermediate 2 2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole To a 4-fluorophenyl)(1H-imidazol-2-yl)methanol (intermediate 1, 1.5 g, 4.22 mmol) in acetic acid (15.0 mL) were added SnCl2(4.8 g, 25.35 mmol) and HCl (12N, 3.0 mL) at rt. The reaction mixture was heated to 120 °C under reflux conditions for 16 h, cooled to rt and concentrated under reduced pressure. The residue was neutralized with NaHCO3 solution and extracted with ethyl acetate (3 × 150 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The resulting crude product was purified by CombiFlash column chromatography (SiO2, 0-80% EtOAc / Hex) to yield the title compound (1.1 g, 77%), LCMS: m / z [M+H]+= 339. Intermediate 3 2- methyl)-4,5-diiodo-1H-imidazole To a solution of 2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole (intermediate 2, 1.5 g, 4.42 mmol) in DMF (20.0 mL) were added KOH (0.5 g, 8.85 mmol) and I2(1.7 g, 6.63 mmol) at 0 °C and the reaction mixture was stirred at rt for 2 h. The reaction mixture was quenched with sodium thiosulfate solution, the aqueous layer was extracted with ethyl acetate (3 × 100 mL). The combined organic layers were washed with brine, dried over Na2SO4and concentrated under reduced pressure. The resulting crude product was purified by CombiFlash column chro- matography (SiO2, 0-40% EtOAc / Hex) to yield the title compound (1.8 g, 69%), LCMS: m / z [M+H]+= 591. 25 GRA 4216-foreign filing Intermediate 4 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-iodo-1H-imidazole To 2-[bis(3-chloro-4-fluorophenyl)methyl]-4,5-diiodo-1H-imidazole (intermediate 3, 2.2 g, 3.72 mmol) in ethanol (25.0 mL) and water (7.0 mL) was added sodium thiosulfate (18.5 g, 74.57 mmol) at rt and the mixture was heated to 110 °C under reflux conditions for 16 h. Sodium thiosulfate (18.5 g, 74.57 mmol) was then added again to the reaction mixture and the mixture was heated to 110 °C for 4 days. The reaction mixture was cooled to rt, diluted with water and extracted with ethyl acetate (2 x 100 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by CombiFlash column chromatography (SiO2, 0-40% EtOAc / Hex) to yield the title compound (1.5 g, 86%), LCMS: m / z [M+H]+= 465. Intermediate 5 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole and the corre- sponding SEM regioisomer To a solution of 2-(bis(3-chloro-4-fluorophenyl) methyl)-4-iodo-1H-imidazole (intermediate 4, 2.0 g, 4.301 mmol) in DMF (15.0 mL) was added NaH (0.343 g, 8.602 mmol, 60% suspension) at 0 °C, the mixture was then stirred at rt for 30 minutes. Then SEM-Cl (1.14 mL, 6.452 mmol) was added after cooling the mixture to 0°C and the mixture was then stirred at rt for 16 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate (3 x 100 mL). The combined organic layers were washed with water, brine, dried over anhydrous Na2SO4and concentrated under reduced pressure. The residue was purified by combi- flash column chromatography (SiO2, 10% EtOAc / Hex) to yield the title compound (2.0 g, 78%), LCMS: m / z [M+H]+= 595. Intermediate 6 4-(benzylthio)-2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole 26 GRA 4216-foreign filing To 4-fluorophenyl)methyl)-4-iodo-1H-imidazole (intermediate 4, 0.4 g, 0.862 mmol) in dioxane (10.0 mL) were added phenylmethanethiol (0.215 g, 1.724 mmol), DIPEA (0.3 mL, 1.724 mmol) and Xanthphos (0.025 g, 0.043 mmol) at rt. The reaction mixture was degassed with argon for 10 min followed by the addition of Pd2(dba)3 (0.025 g, 0.026 mmol) at rt. The reaction mixture was heated to 110 °C for 16 h in a sealed tube. The reaction mixture was cooled to rt and filtered through a celite bed. The filtrate was evaporated under reduced pressure to get the crude product, which was purified by CombiFlash column chromatography (SiO2, 0- 40% EtOAc / Hex) to yield the title compound (0.18 g, 45%), LCMS: m / z [M+H]+= 461. Intermediate 7 The title compound was prepared from the appropriate intermediate using an analogous method to that described for intermediate 6. Intermediate Name / Structure / Data 7 methyl 5-chloro-2-(4,4-difluoropiperidin-1-yl)-6-methylpyridine-3-carboxylate Yield: 0.05 g, 52%. LCMS: m / z [M+H]+= 475. Intermediate 8 2- methyl)-4-(methylthio)-1H-imidazole A solution of 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-iodo-1H-imidazole (intermediate 4, 0.6 g, 1.29 mmol) in NMP (10 mL) was degassed with argon for 15 min followed by the addition of NaSMe (0.18 g, 2.58 mmol) and CuCl2 (0.08 g, 0.64 mmol) at rt. The reaction mixture was heated to 130 °C for 16 h, was then cooled to rt and 27 GRA 4216-foreign filing filtered through a celite bed. The filtrate was concentrated under reduced pressure to get the crude product, which was purified by column chromatography (SiO2, 0-60% EtOAc / Hex) to afford the title compound (0.26 g, 52%), LCMS: m / z [M+H]+= 385. Intermediate 13 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-iodo-5-(methylsulfonyl)-1H-imidazole To (3-chloro-4-fluorophenyl)methyl)-5-(methylsulfonyl)-1H-imidazole (example 1, 1.5 g, 3.606 mmol) in DCM (50.0 mL) was added NIS (1.3 g, 5.40 mmol) at rt. The reaction mixture was stirred at rt for 16 h. The reaction mixture was quenched with sodium thiosulfate solution, the aqueous layer was extracted with ethyl acetate (2 × 100 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure to get a residue which was purified by CombiFlash column chromatography (SiO2, 0-60% EtOAc / Hex) to yield the title compound (1.3 g, 66%), LCMS: m / z [M+H]+= 543. Intermediate 14 bis(3-chloro-4- (5-methyl-1H-imidazol-2-yl)methanol Mg (3.2 g, 129.727 mmol) was taken up in a 2-necked flask equipped with a reflux condenser and dried under argon atmosphere. THF (30.0 mL), 4-bromo-2-chloro-1-fluorobenzene (15.8 mL, 129.727 mmol) and DIBAL (1M in toluene) (2.0 mL) were added to the mixture sequentially at rt. The reaction mixture was stirred at rt for 1 h. To this mixture, a solution of ethyl 4-methyl-1H-imidazole-2-carboxylate (4.0 g, 25.95 mmol) in THF (170.0 mL) was added at 0 °C and the reaction mixture was heated to 80 °C for 5 h. The reaction mixture was cooled to rt and quenched with ammonium chloride solution. The aqueous layer was filtered through a celite bed and extracted with ethyl acetate (3 x 200 mL). The combined organic layers were washed with brine, dried over Na2SO4and concentrated under reduced pressure to get the crude product which was purified by column chromatography (SiO2, 0-60% EtOAc / Hex) to yield the title compound (7.1 g, 74%), LCMS: m / z [M+H]+= 369. 28 GRA 4216-foreign filing Intermediate 15 The title compound was prepared from the appropriate intermediates using an analogous method to that described for intermediate 14. Intermediate Name / Structure / Data 15 (5-chloro-1H-imidazol-2-yl)bis(3-chloro-4-fluorophenyl)methanol Yield: 0.5 g, 37%, LCMS: m / z [M+H]+= 389. Intermediate 16 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-methyl-1H-imidazole To a solution of bis(3-chloro-4-fluorophenyl)(5-methyl-1H-imidazol-2-yl)methanol (intermediate 14, 7.0 g, 19.02 mmol) in acetic acid (100.0 mL) were added SnCl2 (21.6 g, 114.13 mmol) and conc. HCl (21.0 mL) at 0 °C. The reaction mixture was stirred at 120 °C under reflux conditions for 16 h. The reaction mixture was cooled to rt and concentrated under reduced pressure. The resulting crude residue was basified with Na2CO3solution. The aqueous layer was filtered through a celite bed and the filtrate was extracted with ethyl acetate (3 × 200 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure to get the crude product which was washed with 10% ethyl acetate in hexane to obtain the title compound (5.2 g, 77%), LCMS: m / z [M+H]+= 353. Intermediate 17 The title compound was prepared from the appropriate intermediates using an analogous method to that described for intermediate 16. Intermediate Name / Structure / Data 17 (5-chloro-1H-imidazol-2-yl)bis(3-chloro-4-fluorophenyl)methanol 29 GRA 4216-foreign filing Yield: 0.12 g, 50%. LCMS: m / z [M+H]+= 373. Intermediate 18 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-iodo-4-methyl-1H-imidazole To a 2- 4-fluorophenyl)methyl]-5-methyl-1H-imidazole (intermediate 16, 2.5 g, 7.102 mmol) in DMF (30.0 mL) were added KOH (0.6 g, 10.653 mmol) and I2(2.4 g, 9.233 mmol) at 0 °C. The reaction mixture was then stirred at rt for 1 h. The reaction mixture was quenched with sodium thiosulfate solution, the aqueous layer was extracted with ethyl acetate (2 × 150 mL). The combined organic layers were washed with brine, dried over Na2SO4 and evaporated under reduced pressure to get the crude product which was purified by column chromatography (SiO2, 0-40% EtOAc / Hex) to yield the title compound (2.2 g, 64%), LCMS: m / z [M+H]+= 479. Intermediate 19 2- methyl)-4-chloro-5-iodo-1H-imidazole To a stirred solution of 2-[bis(3-chloro-4-fluorophenyl)methyl]-5-chloro-1H-imidazole (intermediate 17, 6.0 g, 16.086 mmol) in DCM (100.0 mL) was added NIS (5.5 g, 24.129 mmol) at rt. The reaction was stirred for 16 h at rt. The reaction mixture was quenched with sodium thiosulfate solution, was diluted with water and extracted with ethyl acetate (2 × 300 mL). The combined organic layers were washed with brine, dried over Na2SO4and concen- trated under reduced pressure to get the crude product, which was purified by CombiFlash column chromatography (SiO2, 0-60% EtOAc / Hex) to yield the title compound (4.2 g, 53%). LCMS: m / z [M+H]+= 499. 30 GRA 4216-foreign filing Intermediate 20 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-methyl-4-(methylthio)-1H-imidazole A 4-fluorophenyl)methyl]-5-iodo-4-methyl-1H-imidazole (intermediate 18, 0.5 g, 1.046 mmol) in dioxane (30.0 mL) was degassed with argon for 10 min followed by the addition of NaSMe (0.11 g, 1.569 mmol), Xanthphos (0.091 g, 0.157 mmol) and Pd2(dba)3 (0.096 g, 0.105 mmol) at rt. The reaction mixture was heated to 110 °C for 16 h in a sealed tube. The reaction mixture was cooled to rt, diluted with ice water and extracted with ethyl acetate (3 x 80 mL). The combined organic layers were washed with brine, dried over Na2SO4and concentrated under reduced pressure to get the crude product, which was purified by column chromatography (SiO2, 0-50% EtOAc / Hex) to yield the title compound (0.23 g, 55%), LCMS: m / z [M+H]+= 399. Intermediate 21 5-chloro-1H-imidazole-2-carboxylate To a solution of ethyl 1H-imidazole-2-carboxylate (5.0 g, 35.71 mmol) in DMF (100.0 mL) was added acetic acid (1.0 mL) at rt. To this mixture was added a solution of NCS (4.7 g, 35.71 mmol) in DMF (100.0 mL) dropwise at 0 °C. The reaction mixture was stirred at rt for 40 h. The reaction mixture was diluted with ice water and extracted with ethyl acetate (3 x 100 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The resulting residue was triturated with acetonitrile to obtain the title com- pound (2.3 g, 36%), LCMS: m / z [M+H]+= 175. Intermediate 22 4- (trimethylsilyl)ethoxy)methyl)-1H-imidazole Sodium hydride (60% dispersion in mineral oil, 0.297 g, 12.372 mmol.) was added to a solution of 4-iodo-1H- imidazole (2.0 g, 10.310 mmol) in DMF (20 mL) at 0 °C. The mixture was stirred at 0 °C for 1 h followed by the addition of 2-(trimethylsilyl)ethoxymethyl chloride (1.829 mL, 10.310 mmol) at 0 °C. The reaction was stirred at 31 GRA 4216-foreign filing rt for 18 h. The reaction mixture was diluted with ice water (10 mL) and extracted with ethyl acetate (20 mL × 2).The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressureto get the crude material which was purified by flash chromatography (SiO2, 0-50% EtOAc / Hex) to afford the title compound (1.7 g, 51%). The title compound was prepared from the appropriate intermediates using an analogous method to that described for intermediate 22. Intermedi- Structure Name Data ate 27 4-iodo-5-methyl-1-((2-(tri- LCMS m / z = 339 [M+H]+. methylsilyl)ethoxy)methyl)- 1H-imidazole and the corre- sponding SEM regioisomer Intermediate 23 (3-chloro-4-fluorophenyl)(4-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methanol and the cor- responding SEM regioisomer LDA (2M sol. in THF / n-heptane / ethylbenzene, 12.383 mL, 24.766 mmol) was added to a solution of 4-iodo-1- ((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole (intermediate 22, 7.3 g, 22.514 mmol) in THF at ^78 °C. The reaction was stirred at ^78 °C for 1 h followed by the addition of 3-chloro-4-fluorobenzaldehyde (3.570 g, 22.514 mmol). The reaction mixture was stirred at ^78 °C for 1 h. The reaction was quenched with sat. NH4Cl solution (50 mL) and extracted with ethyl acetate (100 mL × 2). The combined organic layers were dried over anhydrous Na2SO4, filtered and evaporated to get the crude compound, which was purified by flash chromatography (SiO2, 0-50% EtOAc / Hex) to afford the title compound (7.0 g, 64%). The title compound was prepared from the appropriate intermediates using an analogous method to that described for intermediate 23. Intermedi- Structure Name Data ate 32 GRA 4216-foreign filing 28 (3-chloro-4-fluorophenyl)(4- LCMS m / z = 497 [M+H]+. iodo-5-methyl-1-((2-(trime- thylsilyl)ethoxy)methyl)-1H- imidazol-2-yl)methanol and the corresponding SEM regi- oisomer Intermediate 24 (3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methanol and the corresponding SEM regioisomer L-Proline (262.313 mg, 2.278 mmol) was added to an argon purged solution of sodium hydroxide (91.136 mg, 2.278 mmol) in DMSO (30 mL) and the mixture was stirred at rt for 30 min followed by the addition of (3-chloro- 4-fluorophenyl)(4-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methanol (mixture of regioiso- mers, intermediate 23, 1.1 g, 2.278 mmol), copper(I) iodide (433.922 mg, 2.278 mmol) and sodium methanesul- finate (930.318 mg, 9.114 mmol) at rt. The reaction was heated to 120 °C for 18 h. The reaction mixture was diluted with water (30 mL) and extracted with ethyl acetate (50 mL x 2). The organic layers were evaporated under reduced pressure to yield the title compound (0.65 g, crude), which was used in the next step without further purification. The title compound was prepared from the appropriate intermediates using an analogous method to that described for intermediate 24. Intermedi- Structure Name Data ate 29 (3-chloro-4-fluorophenyl)(5- LCMS m / z = 449 [M+H]+. methyl-4-(methylsulfonyl)- 1-((2-(trimethylsilyl)eth- oxy)methyl)-1H-imidazol-2- yl)methanol and the corre- sponding SEM regioisomer 33 GRA 4216-foreign filing Intermediate 25 (3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methanone and the corresponding SEM regioisomer (3.964 g, 18.392 mmol) was added to a solution of (3-chloro-4-fluorophenyl)(4-(me- thylsulfonyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methanol (mixture of regioisomers, interme- diate 24, 3.0 g, 6.897 mmol) in dichloromethane (90 mL) at 0 °C. The reaction was stirred at rt for 2 h. After completion of the reaction, the reaction mixture was diluted in water (50 mL) and extracted with DCM (2 × 50 mL). The combined organic layers were dried over anhydrous Na2SO4and concentrated under reduced pressure. The crude product was purified by flash chromatography (SiO2, 0-50% EtOAc / Hex) to afford the title compound (1.0 g, 25%). The title compound was prepared from the appropriate intermediates using an analogous method to that described for intermediate 25. Intermedi- Structure Name Data ate 30 (3-chloro-4-fluorophenyl)(5- LCMS m / z = 447 [M+H]+; methyl-4-(methylsulfonyl)- 1-((2-(trimethylsilyl)eth- oxy)methyl)-1H-imidazol-2- yl)methanone and the corre- sponding SEM regioisomer Intermediate 31 2-(bis(3-chloro-4,5-difluorophenyl)methyl)-5-methyl-4-(methylthio)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H- imidazole and the corresponding SEM regioisomer 34 GRA 4216-foreign filing mmol) was taken up in a 2-necked flask equipped with a reflux condenser and dried under an argon atmosphere. THF (30.0 mL) and I2(0.02 g) were added. A solution of 5-bromo-1-chloro-2,3- difluorobenzene (6.64 mL, 52.551 mmol) in THF (10.0 mL) was added dropwise to the reaction mixture. The reaction mixture was stirred at room temperature for 1 h. To the freshly prepared Grignard reagent was added a solution of ethyl 5-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxylate (mixture of regioiso- mers, 3.0 g, 10.51 mmol) in THF (10.0 mL) at 0 °C and the reaction mixture was stirred for 2 h. The reaction mixture was quenched with saturated NH4Cl solution, diluted with EtOAc (150 mL) and washed with H2O (50 mL) and brine (50 mL). The organic extract was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to get the crude product, which was purified by column chromatography (SiO2, 0-20% EtOAc / Hex) to afford bis(3-chloro-4,5-difluorophenyl)(5-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imid- azol-2-yl)methanol and the corresponding SEM regioisomer (5 g, 88%). Step 2: To a stirred solution of bis(3-chloro-4,5-difluorophenyl)(5-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)- 1H-imidazol-2-yl)methanol (mixture of refioisomers, 5.0 g, 9.321 mmol) in acetic acid (20.0 mL) and conc. HCl (10 mL) was added SnCl2(10.6 g, 55.924 mmol) at 0 °C. The reaction mixture was stirred at 120 °C for 16 h. The reaction mixture was concentrated under reduced pressure, the resulting residue was basified with Na2CO3solution and filtered through a pad of celite. The filtrate was extracted with DCM (2 × 100 mL). The combined organic layers were washed with brine (100 mL), dried over Na2SO4 and concentrated under reduced pressure to afford 2- [bis(3-chloro-4,5-difluorophenyl)methyl]-5-methyl-1H-imidazole (2.6 g, 71%). Step 3: To a solution of 2-[bis(3-chloro-4,5-difluorophenyl)methyl]-5-methyl-1H-imidazole (2.2 g, 5.653 mmol) in DMF (20.0 mL) were added KOH (0.476 g, 8.479 mmol) and I2 (1.87 g, 7.349 mmol) at 0 °C. The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was diluted with EtOAc (150 mL) and washed with Na2S2O3solution (50 mL), H2O (50 mL) and brine (50 mL). The organic layer was dried over anhy- drous Na2SO4, filtered and concentrated under reduced pressure to get the crude product, which was purified by column chromatography (SiO2, 0-40% EtOAc / Hex) to afford 2-[bis(3-chloro-4,5-difluorophenyl)methyl]-4-iodo- 5-methyl-1H-imidazole (2.1 g, 72%). Step 4: To a stirred solution of 2-[bis(3-chloro-4,5-difluorophenyl)methyl]-4-iodo-5-methyl-1H-imidazole (0.7 g, 1.359 mmol) in DCM (14 mL) were added DIPEA (0.59 mL, 3.398 mmol) and then SEM-Cl (0.36 mL, 2.039 mmol) dropwise to the reaction mixture at 0 °C. The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure to get crude product, which was purified by flash chromatography (SiO2, 0-20% EtOAc / Hex) to afford 2-(bis(3-chloro-4,5-difluorophenyl)methyl)-4-iodo-5-me- thyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole (0.72 g, 81%). Step 5: A stirred solution of 2-(bis(3-chloro-4,5-difluorophenyl)methyl)-4-iodo-5-methyl-1-((2-(trimethylsi- lyl)ethoxy)methyl)-1H-imidazole (0.5 g, 0.774 mmol) in 1,4-dioxane (10.0 mL) was degassed for 5 minutes in a 35 GRA 4216-foreign filing sealed tube. Then NaSMe (0.108 g, 1.547 mmol), XantPhos (0.022 g, 0.039 mmol) and Pd2(dba)3(0.028 g, 0.031 mmol) were added and the resulting mixture was stirred at 100 °C for 16 h. The reaction mixture was filtered through a pad of celite. The celite pad was washed with EtOAc (100 mL), the filtrate was concentrated under reduced pressure to get crude product. The crude product was purified by column chromatography (SiO2, 0-30% EtOAc / Hex) to afford the title compounds (0.32 g, 73%). LCMS: m / z [M+H]+= 585. The title compounds were prepared from the appropriate intermediates using an analogous method to that described for intermediate 31. Intermedi- Structure Name Data ate 32 2-(bis(2,4-difluoro- LCMS m / z = 529 [M+H]+. phenyl)methyl)-5-methyl-4- (methylthio)-1-((2-(trime- thylsilyl)ethoxy)methyl)-1H- imidazole and the corre- sponding SEM regioisomer 33 2-(bis(5-chloro-2,4-difluoro- LCMS m / z = 565 [M+H]+. phenyl)methyl)-5-methyl-4- (methylthio)-1-((2-(trime- thylsilyl)ethoxy)methyl)-1H- imidazole and the corre- sponding SEM regioisomer 34 2-(bis(4-fluoro-3-(trifluoro- LCMS m / z = 629 [M+H]+. methoxy)phenyl)methyl)-5- methyl-4-(methylthio)-1-((2- (trimethylsilyl)ethoxy)me- thyl)-1H-imidazole and the corresponding SEM regioiso- mer 35 2-(bis(3-chloro-2,4-difluoro- LCMS m / z = 565 [M+H]+. phenyl)methyl)-5-methyl-4- (methylthio)-1-((2-(trime- thylsilyl)ethoxy)methyl)-1H- imidazole and the corre- sponding SEM regioisomer 36 GRA 4216-foreign filing 36 2-(bis(2-chloro-4-fluoro- LCMS m / z = 529 [M+H]+. phenyl)methyl)-5-methyl-4- (methylthio)-1-((2-(trime- thylsilyl)ethoxy)methyl)-1H- imidazole and the corre- sponding SEM regioisomer Intermediate 37 2-(bis(4-chloro-3-fluorophenyl)methyl)-5-methyl-4-(methylthio)-1H-imidazole was heated under vacuum for 5 minutes, then cooled to room temperature. THF (50 mL) was added, followed by the addition of DIBAL-H (1.0 mL). The mixture was stirred at room tempera- ture.4-bromo-1-chloro-2-fluorobenzene (14.3 ml, 116.757 mmol) dissolved in THF (20 mL) and added dropwise to the reaction mixture. The reaction mixture was stirred at room temperature for 1h. The freshly prepared Grignard reagent was cooled at 0 °C, ethyl 5-methyl-1H-imidazole-2-carboxylate (3.6 g, 42.19 mmol) was added and the reaction was stirred at room temperature for 16 h. The reaction was quenched with aqueous NH4Cl solution, ex- tracted with EtOAc and washed with water. The organic layer was washed with brine, dried over anhydrous Na2SO4and concentrated under reduced pressure to get crude product which was purified by column chromatog- raphy (SiO2, 0-60% EtOAc / Hex) to obtain bis(4-chloro-3-fluorophenyl)(5-methyl-1H-imidazol-2-yl)methanol (6.2 g, 72%). LCMS: m / z [M+H]+= 369. Step 2-3 was carried out in analogy to the synthesis of intermediate 31 to obtain the title compounds. LCMS: m / z [M+H]+= 399. The title compound was prepared from the appropriate intermediates using an analogous method to that described for intermediate 37 followed by SEM protection (e.g. intermediate 31, step 4). Intermedi- Structure Name Data ate 38 2-(bis(4-(trifluorometh- LCMS m / z = 593 [M+H]+. oxy)phenyl)methyl)-5-me- thyl-4-(methylthio)-1-((2- (trimethylsilyl)ethoxy)me- thyl)-1H-imidazole and the corresponding SEM regioiso- mer 37 GRA 4216-foreign filing Intermediate 39 2-(bis(4-chloro-2-methoxyphenyl)methyl)-5-methyl-4-(methylthio)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H- imidazoleand the corresponding SEM regioisomer S of 1-bromo-4-chloro-2-methoxybenzene (18 g, 81.08 mmol) in THF (75 mL) was added iPrMgBr (2 M in THF, 41 mL, 81.08 mmol) dropwise at 0 °C and the resulting solution was stirred at 40 °C for 16 h. To this freshly prepared Grignard reagent was added a solution of ethyl 5-methyl-1H-imidazole- 2-carboxylate (2.5 g, 16.22 mmol) in THF (25 mL) at 0 °C and the reaction mixture was then heated to 80 °C for 3 h. The reaction mixture was quenched with ammonium chloride solution. The aqueous part was extracted with ethyl acetate (2 x 200 mL). The combined organic layers were washed with brine (150 mL), dried over Na2SO4and concentrated under reduced pressure to afford the crude product, which was purified by column chromatog- raphy (SiO2, 10% EtOAc / Hex) to afford bis(4-chloro-2-methoxyphenyl)(5-methyl-1H-imidazol-2-yl)methanol. Yield: 39% (2.5 g, 6.36 mmol). LCMS: m / z [M+H]+= 393. Step 2-4 was carried out in analogy to the synthesis of intermediate 31 to obtain the title compounds. LCMS: m / z [M+H]+= 553. Intermediate 40 2-(bis(3-(difluoromethyl)-4-fluorophenyl)methyl)-5-methyl-4-(methylthio)-1-((2-(trimethylsilyl)ethoxy)methyl)- 1H-imidazole and the corresponding SEM regioisomer Step 1: To a stirred solution of 4-bromo-2-(difluoromethyl)-1-fluorobenzene (1 g, 14.01 mmol) in THF (20 mL) was added iPrMgBr (8 mL, 15.77 mmol) at 40 °C. The reaction mixture was stirred at the same temperature for 2 h. The mixture was cooled to 0 °C and ethyl 5-methyl-1H-imidazole-2-carboxylate (2.5 g, 3.503 mmol) in THF (5 mL) was added. The mixture was heated to 80 °C for 4 h. The reaction mixture was cooled to room temperature and quenched with ammonium chloride solution. The aqueous part was extracted with ethyl acetate (2 x 100 mL). The combined organic layers were washed with brine (100 mL), dried over Na2SO4 and concentrated under re- duced pressure to afford bis(3-(difluoromethyl)-4-fluorophenyl)(5-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)- 1H-imidazol-2-yl)methanol. Yield: Crude (1 g). LCMS: m / z [M+H]+= 531. 38 GRA 4216-foreign filing Step 2: To a stirred solution of bis(3-(difluoromethyl)-4-fluorophenyl)(5-methyl-1-((2-(trimethylsilyl)ethoxy)me- thyl)-1H-imidazol-2-yl)methanol (4.5 g, 8.46 mmol) in acetic acid (50 mL) was added SnCl2(9.63 g, 50.79 mmol) followed by conc. HCl (12N, 10 mL) at room temperature. The reaction mixture was stirred at 110 °C for 16 h. The reaction mixture was concentrated under reduced pressure. The obtained residue was neutralized with Na2CO3 solution, the mixture was filtered and extracted with ethyl acetate (2 × 300 mL). The combined organic layers were washed with water (200 mL) followed by brine (200 mL), dried over Na2SO4and concentrated under reduced pressure to afford the crude product, which was purified by column chromatography (SiO2, 10% EtOAc / Hex) to afford 5,5'-((5-methyl-1H-imidazol-2-yl)methylene)bis(2-fluorobenzaldehyde) and 5-((3-(difluoromethyl)-4- fluorophenyl)(5-methyl-1H-imidazol-2-yl)methyl)-2-fluorobenzaldehyde. Yield: 10% over 2 steps (1.8 g, 1.176 mmol). LCMS: m / z [M+H]+= 341 / 363. Step 3: To a solution of 5,5'-((5-methyl-1H-imidazol-2-yl)methylene)bis(2-fluorobenzaldehyde) and 5-((3-(difluo- romethyl)-4-fluorophenyl)(5-methyl-1H-imidazol-2-yl)methyl)-2-fluorobenzaldehyde (2.2 g, 3.13 mmol) in DCM (40 mL) was added DIPEA (1.4 mL, 7.83 mmol) followed by SEM-Cl (0.8 mL, 4.69 mmol) at 0 °C. The resulting reaction mixture stirred at room temperature for 16 h. The reaction mixture was poured into ice water and extracted with ethyl acetate (2 × 90 mL). The combined organic layers were washed with water (70 mL) followed by brine (60 mL), dried over Na2SO4 and concentrated under reduced pressure to afford the crude product. The obtained residue was purified by column chromatography (SiO2, 10% EtOAc / Hex) to afford 5,5'-((5-methyl- 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methylene)bis(2-fluorobenzaldehyde), 5-((3-(difluorome- thyl)-4-fluorophenyl)(5-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methyl)-2-fluorobenzal- dehyde and the corresponding SEM regioisomers. Yield: 97% (1.5 g, 3.049 mmol). LCMS: m / z [M+H]+= 471 / 493. Step 4: To a stirred solution of 5,5'-((5-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)meth- ylene)bis(2-fluorobenzaldehyde) and 5-((3-(difluoromethyl)-4-fluorophenyl)(5-methyl-1-((2-(trimethylsilyl)eth- oxy)methyl)-1H-imidazol-2-yl)methyl)-2-fluorobenzaldehyde (mixture of regioisomers, 1.8 g, 3.65 mmol) in DCM (24 mL) was added DAST (1.5 mL, 10.94 mmol) at 0 °C. The reaction mixture was stirred for 3 h. Thereaction mixture was quenched with NaHCO3 (100 mL) solution and extracted with DCM (3 × 100 mL). Thecombined organic layers were washed with water (100 mL) followed by brine (50 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford 2-(bis(3-(difluoromethyl)-4-fluorophenyl)methyl)-5-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole and the corresponding SEM regioisomer. Yield: 37%(700 mg, 1.36 mmol). LCMS: m / z [M+H]+= 515. Step 5: To a solution of 2-(bis(3-(difluoromethyl)-4-fluorophenyl)methyl)-5-methyl-1-((2-(trimethylsilyl)eth- oxy)methyl)-1H-imidazole (mixture of regioisomers, 550 mg, 1.067 mmol) in MeCN (10 mL) was added NIS (0.312 g, 1.38 mmol) at 0 °C. The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was poured into ice water (100 mL) and quenched with sodium thiosulfate solution. The resulting aqueous layer was extracted with ethyl acetate (2 × 70 mL). The combined organic layers were washed with cold water (50 mL) followed by brine (50 mL), dried over Na2SO4and concentrated under reduced pressure to afford the crude product, which was triturated with hexane to afford 2-(bis(3-(difluoromethyl)-4-fluorophenyl)methyl)-4-iodo-5-methyl-1- ((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole and the corresponding SEM regioisomer. Yield: 59% (400 mg, 0.624 mmol). LCMS: m / z [M+H]+= 641. 39 GRA 4216-foreign filing Step 6: A stirred solution of 2-(bis(3-(difluoromethyl)-4-fluorophenyl)methyl)-4-iodo-5-methyl-1-((2-(trime- thylsilyl)ethoxy)methyl)-1H-imidazole (mixture of regioisomers, 440 mg, 0.685 mmol) in 1,4-dioxane (10 mL) was degassed with argon for 10 minutes followed by the addition of NaSMe (62 mg, 0.891 mmol), Xantphos (28 mg, 0.048 mmol) and Pd2(dba)3 (31 mg, 0.0.034 mmol) at room temperature. The reaction mixture was heated to 80 °C for 16 h in a sealed tube. The reaction mixture was filtered and the filtrate was concentracted. The obtained residue was diluted with water (50 mL) and extracted with ethyl acetate (2 × 70 mL). The combined organic layers were washed with brine (50 mL), dried over Na2SO4 and concentrated under reduced pressure to afford the crude product, which was purified by column chromatography (SiO2, 10% EtOAc / Hex) to afford the title compounds. Yield: 78% (300 mg, 0.536 mmol). LCMS: m / z [M+H]+= 571. Intermediate 41 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-iodo-4-(methylthio)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidaz- ole and the corresponding SEM regioisomer Step 1: A stirred solution of 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)- 1H-imidazole (intermediate 5, 5 g, 8.39 mmol) in 1,4-dioxane (100 mL) was degassed with argon for 10 min followed by the addition of NaSMe (0.9 g, 12.59 mmol), Xanthphos (0.73 g, 1.26 mmol) and Pd2(dba)3(0.8 g, 0.84 mmol) at room temperature. The reaction mixture was heated to 80 °C for 16 h in a sealed tube. The reaction mixture was filtered and the filtrate was concentracted. The obtained residue was diluted with water (70 mL) and extracted with ethyl acetate (2 × 100 mL). The combined organic layers were washed with brine (60 mL), dried over Na2SO4and concentrated under reduced pressure to afford the crude product, which was purified by column chromatography (SiO2, 10% EtOAc / Hex) to afford 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(methylthio)-1-((2- (trimethylsilyl)ethoxy)methyl)-1H-imidazole and the corresponding SEM regioisomer (3.5 g, 81%). LCMS: m / z [M+H]+= 515. Step 2: To a stirred solution of 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(methylthio)-1-((2-(trimethylsilyl)eth- oxy)methyl)-1H-imidazole (mixture of regioisomers, 3.5 g, 6.79 mmol) in DCM (90 mL) was added NIS (2.3 g, 10.18 mmol) at 0 °C. The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was quenched with aqueous sodium thiosulfate solution (60 mL). The aqueous layer was extracted with ethyl acetate (2 × 130 mL). The combined organic layers were washed with brine (60 mL), dried over Na2SO4and concentrated under reduced pressure to get the crude product, which was purified by flash column chromatography (SiO2, 10% EtOAc / Hex) to afford the title compounds (2.5 g, 57%). LCMS: m / z [M+H]+= 641. 40 GRA 4216-foreign filing Intermediate 42 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-iodo-4-((4-methoxybenzyl)thio)-1H-imidazole S PMB F Cl 1H-imidazole-2-carboxylate (3.0 g, 13.699 mmol) in 1,4-dioxane (100 mL) was added DIPEA (7.2 mL, 41.096 mmol) at room temperature. The reaction mixture was degassed with argon for 10 min followed by the addition of (4-methoxyphenyl)methanethiol (5.8 mL, 41.096 mmol), Xantphos (0.8 g, 1.37 mmol) and Pd2(dba)3(0.63 g, 0.685 mmol) at room temperature. The reaction mixture was heated to 110 °C for 30 h in a sealed tube. The reaction mixture was cooled room temperature, diluted with ethyl acetate and filtered through a celite bed. The filtrate was evaporated under reduced pressure. The resulting crude was purified by column chromatography (SiO2, 0-50% EtOAc / Hex) to yield ethyl 4-{[(4-methoxyphenyl)methyl]sulfanyl}-1H- imidazole-2-carboxylate. Yield: 87% (3.5 g). LCMS: m / z [M+H]+= 293. Step 2: Mg (4.6 g, 188.35 mmol) was taken up in a 2-neck flask equipped with a reflux condenser and was dried under an argon atmosphere. THF (40 mL), 4-bromo-2-chloro-1-fluorobenzene (23.0 mL, 188.35 mmol) and DIBAL-H (1M in toluene, 3.0 mL) were added to the mixture sequentially at room temperature. The reaction mixture was stirred at room temperature for 1 h. To the freshly prepared Grignard reagent was added a solution of ethyl 4-((4-methoxybenzyl)thio)-1H-imidazole-2-carboxylate (11.0 g, 37.67 mmol) in THF (260 mL) at 0 °C and the reaction mixture was heated to 80 °C for 5 h. The reaction mixture was cooled to room temperature and was quenched with ammonium chloride solution. The aqueous layer was filter through a celite bed and extracted with ethyl acetate (3 × 200 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concen- trated under reduced pressure. The resulting crude was purified by column chromatography (SiO2, 0-60% EtOAc / Hex) to yield bis(3-chloro-4-fluorophenyl)(5-{[(4-methoxyphenyl)methyl]sulfanyl}-1H-imidazol-2- yl)methanol. Yield: 58% (11.0 g). LCMS: m / z [M+H]+= 507. Step 3: To a solution of bis(3-chloro-4-fluorophenyl)(5-{[(4-methoxyphenyl)methyl]sulfanyl}-1H-imidazol-2- yl)methanol (10.0 g, 19.724 mmol) in acetic acid (150 mL) were added SnCl2(22.4 g, 118.343 mmol) and HCl (12N, 30 mL) at 0 °C. The reaction mixture was stirred at 120 °C for 16 h. The reaction mixture was cooled to room temperature and was concentrated under reduced pressure to get the crude compound which was basified with Na2CO3solution. The aqueous layer was filter through a celite bed and was extracted with ethyl acetate (3 × 200 mL). The combined organic layers were washed with brine, dried over Na2SO4and concentrated under reduced pressure. The resulting residue was purified by column chromatography (SiO2, 0-60% EtOAc / Hex) to yield 2- [bis(3-chloro-4-fluorophenyl)methyl]-5-{[(4-methoxyphenyl)methyl]sulfanyl}-1H-imidazole. Yield: 41% (4.0 g). LCMS: m / z [M+H]+= 491. Step 4 : To a stirred solution of 2-[bis(3-chloro-4-fluorophenyl)methyl]-5-{[(4-methoxyphenyl)methyl]sulfanyl}- 1H-imidazole (1.0 g, 2.04 mmol) in DCM (20 mL) was added NIS (0.55 g, 2.5 mmol) at 0 °C and the mixture was stirred at for 3 h. The reaction mixture was quenched with sodium thiosulfate solution. The aqueous layer was 41 GRA 4216-foreign filing extracted with ethyl acetate (2 × 50 mL). The combined organic layers were washed with brine, dried over Na2SO4and evaporated under reduced pressure to get the crude product, which was purified by column chromatography (SiO2, 0-60% EtOAc / Hex) to yield the title compounds. Yield: 64% (0.8 g). LCMS: m / z [M+H]+= 617. Intermediate 43 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-iodo-5-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole and the corresponding SEM regioisomer To a stirred solution of 2-[bis(3-chloro-4-fluorophenyl)methyl]-4-iodo-5-methyl-1H-imidazole (12 g, 25.05 mmol) in DCM (120 mL) was added DIPEA (11 mL, 62.62 mmol) followed by SEM-Cl (6.7 mL, 37.57 mmol) dropwise at 0 °C. The resulting reaction mixture was stirred at room temperature for 16 h. The reaction mixture was quenched with cold ammonium chloride solution (100 mL) and extracted with ethyl acetate (2 × 150 mL). The combined organic layers were washed with brine (150 mL), dried over Na2SO4and concentrated under re- duced pressure to afford the crude product, which was purified by column chromatography (SiO2, 10% EtOAc / Hex) to afford the title compounds. Yield: 79% (12 g). LCMS: m / z [M+H]+= 609. Intermediate 44 3-chloro-6-((4-chlorophenyl)(4-(methylthio)-1H-imidazol-2-yl)methyl)-2-(trifluoromethyl)pyridine Step 1: To a solution of 3,6-dichloro-2-(difluoromethyl)pyridine (2.5 g, 11.628 mmol) in ethanol (50 mL) was added TEA (2 mL, 13.953 mmol). The mixture was degassed with nitrogen for 10 minutes, followed by the addi-tion of potassium vinyltrifluoroborate (1.9 g, 13.953 mmol) followed by the addition of PdCl2(dppf) DCM (0.43g, 0.581 mmol) at room temperature. The mixture was then heated to 110 °C for 3 h in a sealed flask. The reaction mixture was cooled to room temperature and filtered through a celite bed, the filtrate was evaporated at low tem- perature (below 40 °C) under reduced pressure. The resulting residue was purified by column chromatography(SiO2, Hex) to get 3-chloro-6-ethenyl-2-(trifluoromethyl)pyridine Yield: 75% (1.8 g).Step 2: To a solution of 3-chloro-6-ethenyl-2-(trifluoromethyl) pyridine (1.8 g, 8.696 mmol) in 1,4-dioxane-water (3:1, 60 mL) was added NMO (2.6 mL, 9.565 mmol, 50% in water) followed by OsO4 (1.2 mL, 0.174 mmol, 0.15 M in Dioxane) at room temperature. The mixture was stirred for 3 h. Then, NaIO4(19 g, 86.957 mmol) was added 42 GRA 4216-foreign filing and the mixture was stirred for 1 h. The mixture was quenched with saturated sodium bi-carbonate solution and extracted with EtOAc (3 x 100 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, concentrated under reduced pressure to get 5-chloro-6-(trifluoromethyl)picolinaldehyde. Yield: 82% (1.5 g). Step 3: To a solution of 5-chloro-6-(trifluoromethyl) picolinaldehyde (0.1 g, 0.478 mmol) in THF (4 mL), was added (4-chlorophenyl) magnesium bromide (1M in Et2O, 0.57 mL, 0.574 mmol) slowly at 0 °C, and the mixture was stirred for 1 h. The reaction mixture was quenched with saturated aqueous ammonium chloride solution and extracted with EtOAc (2 x 20 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4and concentrated to get the crude product, which was purified by column chromatography (SiO2, 30%EtOAc / Hex) to get [5-chloro-6-(trifluoromethyl)pyridin-2-yl](4-chlorophenyl)methanol. Yield: 84% (0.13 g).LCMS: m / z [M+H]+= 322. Step 4: To a solution of [5-chloro-6-(trifluoromethyl) pyridin-2-yl] (4-chlorophenyl) methanol (0.13 g, 0.404 mmol) in THF (5 mL) was added MnO2(0.18 g, 2.019 mmol) at room temperature and the mixture was stirred for 16 h. The mixture was filtered through a celite bed, which was washed with THF. The filtrate was evaporated toget the crude compound which was purified by column chromatography (SiO2, 20% EtOAc / Hex) to get 3-chloro-6-[(4-chlorophenyl) carbonyl]-2-(trifluoromethyl)pyridine. Yield: 77% (0.1 g) Step 5: To a solution of DIPA (0.72 mL, 5.156 mmol) in THF (10 mL) was added n-BuLi (2.3 mL, 2 M in THF, 4.688 mmol) slowly at -78 °C under a nitrogen atmosphere. The mixtue was stirred for 10 minutes at -78 °C, then at 0 °C for 30 minutes. The solution was cooled back to -78 °C, 4-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H- imidazole (mixture of regioisomers, 1.3 g, 3.906 mmol) in THF (10 mL) was added. The mixture was stirred for 30 minutes, followed by the addition of 3-chloro-6-[(4-chlorophenyl)carbonyl]-2-(trifluoromethyl)pyridine (0.5 g, 1.563 mmol) in THF (10 mL) at the same temperature. Thew mixture was slowly warm up to room temperature and was stirred for 6 h. The mixture was quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate (2 x 100 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, concentrated under reduced pressure to get the crude compound which was purified by column chromatography(SiO2, 10% EtOAc / Hex) to get (5-chloro-6-(trifluoromethyl)pyridin-2-yl)(4-chlorophenyl)(4-iodo-1-((2-(trime-thylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methanol and the corresponding SEM regioisomer. Yield: 50% (0.5 g). LCMS: m / z [M+H]+= 645. Step 6: To a solution of (5-chloro-6-(trifluoromethyl)pyridin-2-yl)(4-chlorophenyl)(4-iodo-1-((2-(trimethylsi- lyl)ethoxy)methyl)-1H-imidazol-2-yl)methanol (mixture of regioisomers, 0.5 g, 0.776 mmol) in 1,4-dioxane (20 mL) was added NaSMe (0.1 g, 1.32 mmol) and the mixture was degassed with nitrogen for 10 minutes. Then Xantphos (0.07 g, 0.116 mmol) and Pd2(dba)3 (0.07 g, 0.078 mmol) were added at room temperature and the mixture was heated to 110 °C for 16 h in a sealed tube. The mixture was filtered through a celite bed and the celite bed was washed with EtOAc. The solvent was evaporated to get the crude compound which was purified by col-umn cromatography (SiO2, 10% EtOAc / Hex) to get (5-chloro-6-(trifluoromethyl)pyridin-2-yl)(4-chlorophenyl)(4-(methylsulfonyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methanol and the corresponding SEM regioisomer. Yield: 68% (0.3 g). LCMS: m / z [M+H]+= 564. 43 GRA 4216-foreign filing Step 7: To a solution of (5-chloro-6-(trifluoromethyl)pyridin-2-yl)(4-chlorophenyl)(4-(methylsulfonyl)-1-((2-(tri- methylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methanol (mixture of regioisomers, 0.32 g, 0.566 mmol) in acetic acid (5.0 mL) were added SnCl2 (0.64 g, 3.398 mmol) and aqueous HCl (1 mL, 12N). The mixture was heated to 120 °C for 24 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to get the crude compound which was basified with aqueous Na2CO3solution. The mixture was filtered through a celite bed and was extracted with ethyl acetate (3 × 50 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure to get the crude compound which was purified bycombi-flash column chromatography (SiO2, 50% EtOAc / Hex) to get the title compound. Yield: 55% (0.13 g).LCMS: m / z [M+H]+= 418. Intermediate 45 5-((3-chloro-4-fluorophenyl)(4-(methylthio)-1H-imidazol-2-yl)methyl)-2-(2,2,2-trifluoroethoxy)pyridine Step 1: To a solution of (3-chloro-4-fluorophenyl)(4-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2- yl)methanol (intermediate 23, 4.2 g, 8.699 mmol) in dichloromethane (50 mL) was added celite (1.6 g) followed by pyridinium chlorochromate (3.750 g, 17.399 mmol) at room temperature under an argon atmosphere. The re- sulting reaction mixture was stirred for 16 h. The reaction mixture was filtered through a celite bed, which was washed with DCM (300 mL). The filtratre was concentrated under reduced pressure to afford the crude product. (3 g) crude. The reaction was in parallel carried out with another 0.5 g of (3-chloro-4-fluorophenyl)(4-iodo-1-((2- (trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methanol in analogy. The two crude materials were combined and purified by column chromatography (SiO2, 0-10% EtOAc / Hex) to afford (3-chloro-4-fluorophenyl)(4-iodo- 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methanone (2.1 g, crude). Step 2: (3-Chloro-4-fluoro phenyl)(4-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methanone (10 g, 20.800 mmol) was dissolved in HCl in 1,4-dioxane (4N, 200 mL) at 0 °C. The resulting mixture was stirred at room temperature for 5 h. The reaction mixture was concentrated under reduced pressure and was then diluted with water (5 mL) and basified with NaHCO3 solution (pH=8) at 0 °C. After stirring for 10 min, the resulting precipitate was filtered off and dried under reduced pressure to afford (3-chloro-4-fluorophenyl)(4-iodo-1H-imid- azol-2-yl)methanone (7.5 g, crude). Step 3: (3-Chloro-4-fluorophenyl)(4-iodo-1H-imidazol-2-yl)methanone (3 g, 8.559 mmol) and sodium thiometh- oxide (0.600 g, 8.559 mmol) were dissolved in 1,4-dioxane (30 mL) followed by the addition of cesium carbonate (8.366 g, 25.676 mmol). The mixture was then degassed with argon for 10 min. Then Pd2(dba)3(0.784 g, 0.856 mmol) followed by Xantphos (0.495 g, 0.856 mmol) were added at room temperature. The resulting reaction mix- ture was heated to 120 °C for 16 h. The reaction mixture was cooled to room temperature, filtered through a celite bed and the celite bed was washed with 250 mL of ethyl acetate. The filtrate was concentrated under reduced 44 GRA 4216-foreign filingpressure. The crude product was purified by column chromatography (SiO2, 13% EtOAc / pet ether) to afford (3-chloro-4-fluorophenyl)(4-(methylthio)-1H-imidazol-2-yl)methanone (0.560 g, 24%). Step 4: 2-Bromo-5-(2,2,2-trifluoroethoxy)pyridine (7.944 g, 31.030 mmol) was added to a vigorous stirred solu- tion of magnesium turnings (0.754 g, 31.030 mmol) and iodine (5.250 mg, 0.021 mmol) in anhydrous tetrahydro- furan (10 mL) at room temperature under an argon atmosphere. The resulting suspension was stirred for 1 h. The reaction mixture was cooled to 0 °C and a solution of (3-chloro-4-fluorophenyl)(4-(methylthio)-1H-imidazol-2- yl)methanone (0.56 g, 2.069 mmol) in anhydrous tetrahydrofuran (10 mL) was addeddrop wise. The resulting re- action mixture was warmed to room temperature and stirred for 1 h. The reaction mixture was quenched by the addition of sat. solution of NH4Cl (20 mL) at 0 °C and extracted with ethyl acetate (2×30 mL). The combined organic layers were dried over anhydrous Na2SO4and evaporated under reduced pressure. The crude product waspurified by column chromatography (SiO2, 40% EtOAc / pet ether) to afford (3-chloro-4-fluorophenyl)(4-(methyl-thio)-1H-imidazol-2-yl)(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methanol (455 mg, crude). Step 5: Stannous chloride dihydrate (1.36 g, 6.029 mmol) was added to a stirred solution of (3-chloro-4-fluoro- phenyl)(4-(methylthio)-1H-imidazol-2-yl)(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methanol (450 mg, 1.005 mmol) and conc. HCl (1 mL) in acetic acid (5.2 mL) at room temperature. The resulting reaction mixture was heated to 100 °C for 16 h. he reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was diluted with ice-cold water (20 mL), basified with solid NaHCO3(pH= 8) and diluted with EtOAc (80 mL). The resulting suspension was filtered through celite, the organic phase vwas separated, dried over anhy- drous Na2SO4 and concentrated under reduced pressure to afford 5-((3-chloro-4-fluorophenyl)(4-(methylthio)-1H- imidazol-2-yl)methyl)-2-(2,2,2-trifluoroethoxy)pyridine (360 mg, crude). Step 6: Sodium hydride (69.471 mg, 1.737 mmol) was added in a solution of 5-((3-chloro-4-fluorophenyl)(4-(me- thylthio)-1H-imidazol-2-yl)methyl)-2-(2,2,2-trifluoroethoxy)pyridine (300 mg, 0.695 mmol) in THF (6 mL) at 0 °C under an argon atmosphere. The reaction was stirred at 0 °C for 5 min followed by the addition of SEMCl (0.308 mL, 1.737 mmol) at 0 °C. The mixture was stirred for 15 min. The reaction was diluted with ice water (10 mL) and extracted with ethyl acetate (3×25 mL). The solvent was evaporated under reduced pressure to afford the title compound (570 mg, crude). Intermediate 46 3-chloro-5-((3-chloro-4-fluorophenyl)(4-(methylthio)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2- yl) - and the corresponding SEM regioisomer Step 1: To a stirred solution of 2-iodo-1H-imidazole (3.0 g, 15.466 mmol) in THF (30 mL) at 0 °C was added sodium hydride (60% dispersion in mineral oil, 1.237 g, 18.559 mmol) and the mixture was stirred for 1 h followed 45 GRA 4216-foreign filing by addtion of SEMCl (2.743 mL, 15.466 mmol). The resulting reaction mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with cold water (50 mL) and extracted with EtOAc (50 mL x 2). The combined organic layers were dried over sodium sulphate and the solvent was evaporated under reduced pressure to get crude compound, which was purified by column column (SiO2, 0-50% EtOAc / Hex) to afford 2-iodo-1-((2- (trimethylsilyl)ethoxy)methyl)-1H-imidazole and the corresponding SEM regioisomer (3.5 g, 70%). Step 2: To a stirred solution of methyl 5,6-dichloronicotinate (4 g, 19.415 mmol) in MeCN (10 mL) at room tem- perature was added trimethylsilyl iodide (4.162 mL, 29.122 mmol). The resulting reaction mixture was stirred at 80 °C for 4 h. The reaction mixture was cooled to room temperature, basified with aq. sodium bicarbonate (50 mL) and extracted with EtOAc (100 mL x 2). The combined organic layers were washed with aq. sodium thiosul- fate (100 mL) and concentrated under reduced pressure to get methyl 5-chloro-6-iodonicotinate (5.0 g, 86%). Step 3: To a stirred solution of methyl 5-chloro-6-iodonicotinate (1.0 g, 3.362 mmol) and copper iodide (2.561 g, 13.446 mmol) in DMF (10.0 mL) at room temperature was added methyl 2,2-difluoro-2-(fluorosulfonyl) acetate (4.198 g, 21.851 mmol). The resulting reaction mixture was heated to 80 °C for 18 h. The reaction mixture was cooled to room temperature, diluted with water (50 mL) and extracted with EtOAc (50 mL x 2). The combined organic layers were dried over sodium sulphate and concentrated under reduced pressure to get the crude product, which was purified via column chromatography (SiO2, 10% EtOAc / pet ether) to obtain (3-chloro-4-fluorophenyl) (4-iodo-5-methyl-1-((2-(trimethylsilyl) ethoxy) methyl)-1H-imidazol-2-yl) methyl diisopropylcarbamate (2.8 g, 93%). Step 4: Lithium hydroxide hydrate (262.724 mg, 6.261 mmol) was added to stirred solution of methyl 5-chloro-6- (trifluoromethyl) nicotinate (500 mg, 2.087 mmol) in methanol (4 mL), THF (4 mL) and water (2 mL) at room temperature. The reaction mixture was stirred for 2 h. The solvent was removed under reduced pressure to obtain a residue, which was neutralised with 20% HCl solution (ph=3) and extracted with ethyl acetate (20 mL x 3). The combined organic layers were evaporated under reduced pressure to obtain 5-chloro-6-(trifluoromethyl) nicotinic acid (0.4 g, crude). Step 5: DIPEA (0.238 mL, 1.330 mmol) was added to a stirred solution of 5-chloro-6-(trifluoromethyl) nicotinic acid (100 mg, 0.443 mmol), HATU (252.867 mg, 0.665 mmol) and N, O-dimethylhydroxylamine hydrochloride (64.874 mg, 0.665 mmol) in DMF (5 mL) at room temperature. The reaction mixture was stirred for 4 h. The reaction reaction mass was diluted with water (5 mL) and extracted with ethyl acetate (10 mL x 2). The combined organic layers were dried over sodium sulphate and evaporated under reduced pressure to get the crude product, which was purified by column chromatography (SiO2, 0-50% EtOAc / pet ether) to afford 5-chloro-N-methoxy-N- methyl-6-(trifluoromethyl) nicotinamide (0.08 g, 93%). Step 6: 4-Bromo-2-chloro-1-fluorobenzene (19.492 g, 93.068 mmol) was added to a stirred solution of magnesium turnings (2.457 g, 102.375 mmol) and iodine (10 mg) in THF (30 mL) at room temperature. The reaction mixture was stirred for 30 min and was then cooled to 0 °C.5-Chloro-N-methoxy-N-methyl-6-(trifluoromethyl)nicotina- mide (5.0 g, 18.614 mmol) in THF (20 mL) was added and the mixture was stirred for 30 min. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (100 mL x 2). The combined organic layers were dried over sodium sulphate and evaporated under reduced pressure to get the crudecompound, which was purified 46 GRA 4216-foreign filing by column chromatography (SiO2, 0-50% EtOAc / pet ether) to obtain (3-chloro-4-fluorophenyl) (5-chloro-6-(tri- fluoromethyl) pyridin-3-yl) methanone (2.7 g, 46%). Step 7: To a stirred solution of 2-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole (mixture of regioiso- mers, 2.9 g, 8.944 mmol) in THF (30 mL) at -78 °C was added n-BuLi (1.6M solution in hexanes, 5.366 mL, 13.416 mmol) and the mixture was stirred for 30 min. Then (3-chloro-4-fluorophenyl) (5-chloro-6-(trifluorome- thyl) pyridin-3-yl)methanone (1.512 g, 4.472 mmol) in THF (10 mL) was added. The resulting mixture was stirred at -78 °C for 1.5 h. The reaction mixture was diluted with water (30 mL) and extracted with ethyl acetate (50 mL x 2). The combined organic layers were dried over sodium sulphate and evaporated under reduced pressure to get the crude com pound, which was purified by column chromatography (SiO2, 0-50% EtOAc / pet ether) to afford (3-chloro-4-fluorophenyl) (5-chloro-6-(trifluoromethyl) pyridin-3-yl) (1-((2-(trimethylsilyl)ethoxy)me- thyl)-1H-imidazol-2-yl)methanol and the corresponding SEM regioisomer (2.7g, 56%). Step 8: To a stirred solution of (3-chloro-4-fluorophenyl) (5-chloro-6-(trifluoromethyl) pyridin-3-yl) (1-((2-(tri- methylsilyl) ethoxy) methyl)-1H-imidazol-2-yl) methanol (mixture of regioisomers, 350 mg, 0.652 mmol), acetic acid (7 mL, 0.125 mmol) and HCl (37% solution in water, 5 mL, 0.025 mmol) at room temperature was added stannous chloride dihydrate (1.472 g, 6.525 mmol). The resulting reaction mixture was stirred at 120 °C for 18 h. The reaction mixture was concentrated under reduced pressure, the residue was basified with sat solution of Na- HCO3 and extracted with ethyl acetate (30 mL x 2). The combined organic layers were dried over sodium sulphate and evaporated under reduced pressure to get the crude product, which was purified by column chromatography (SiO2, 0-50% EtOAc / pet ether) to afford 3-chloro-5-((3-chloro-4-fluorophenyl) (4,5-diiodo-1H-imidazol-2-yl) methyl)-2-(trifluoromethyl) pyridine (0.25 g, 98%). Step 9: NIS (562.240 mg, 2.499 mmol) was added to a stirred solution of 3-chloro-5-((3-chloro-4-fluorophenyl) (1H-imidazol-2-yl) methyl)-2-(trifluoromethyl) pyridine (650 mg, 1.666 mmol) in chloroform (10 mL) at 0 °C. The reaction mixture was stirred for 2 h at room temperature. The reaction mixture was diluted with water (10 mL) and extracted with DCM (20 mL x 2). The combined organic layers were dried over sodium sulphate and evaporated under reduced pressure to get the crude compound, which was purified by column chromatography (SiO2, 0-50% EtOAc / pet ether) to afford 3-chloro-5-((3-chloro-4-fluorophenyl) (4,5-diiodo-1H-imidazol-2-yl) methyl)-2-(trifluoromethyl) pyridine (1.0 g, 93%). Step 10: Sodium sulfite (1.963 g, 15.577 mmol) was added to a stirred solution of 3-chloro-5-((3-chloro-4-fluoro- phenyl) (4,5-diiodo-1H-imidazol-2-yl) methyl)-2-(trifluoromethyl) pyridine (1.0 g, 1.558 mmol) in ethanol (7 mL) and water (3 mL) at room temperature. The resulting reaction mixture was heated to 110 °C for 18 h. The reaction mixture was concentrated under reduced pressure, the obtained residue was taken up in water (10 mL) and ex- tracted with ethyl acetate (20 mL x 2). The combined organic layers were dried over sodium sulphate and evapo- rated under reduced pressure to get the crude compound, which was purified by column chromatography (SiO2, 0- 50% EtOAc / pet ether) to afford 3-chloro-5-((3-chloro-4-fluorophenyl) (4-iodo-1H-imidazol-2-yl) methyl)-2-(tri- fluoromethyl) pyridine (0.75 g, 93%). Step 11: Sodium hydride (60% dispersion in mineral oil, 51.157 mg, 1.279 mmol) was added to a stirred solution of 3-chloro-5-((3-chloro-4-fluorophenyl) (4-iodo-1H-imidazol-2-yl) methyl)-2-(trifluoromethyl) pyridine (550 47 GRA 4216-foreign filing mg, 1.066 mmol) in THF (5 mL) at 0 °C and the reaction mixture was stirred for 1 h. Then SEM-Cl (0.284 mL, 1.599 mmol) was added dropwise. The resulting reaction mixture was stirred for 2 h at room temperature. The reaction mixture was quenched with water (10 mL) and extracted with ethyl acetate (20 mL x 2). The combined organic layers were dried over sodium sulphate and evaporated under reduced pressure to get the crude compound, which was purified by column chromatography (SiO2, 0-50% EtOAc / pet ether) to afford 3-chloro-5-((3-chloro-4- fluorophenyl) (4-iodo-1-((2-(trimethylsilyl) ethoxy) methyl)-1H-imidazol-2-yl) methyl)-2-(trifluoromethyl) pyri- dine and the corresponding SEM regioisomer (0.4 g, 80%). Step 12: Pd2(dba)3 (56.673 mg, 0.062 mmol) and Xantphos (71.620 mg, 0.124 mmol) were added to an argon purged solution of 3-chloro-5-((3-chloro-4-fluorophenyl) (4-iodo-1-((2-(trimethylsilyl) ethoxy) methyl)-1H-imid- azol-2-yl) methyl)-2-(trifluoromethyl) pyridine (mixture of regioisomers, 800 mg, 1.238 mmol), sodium thiometh- oxide (104.107 mg, 1.485 mmol) and cesium carbonate (1.210 g, 3.713 mmol) in 1,4-dioxane (10 mL) at room temperature. The reaction mixtre was stirred for 1 h under microwave irradiation at 120 °C. The reaction mixture was filtered through a pad of celite and the celite pad was washed with ethyl acetate (2 x 30 mL). The filtrate was evaporated under reduced pressure to get the crude compound, which was purified by column chromatography (SiO2, 0-50% EtOAc / pet ether) to get the title compounds (0.7 g, crude). Intermediate 47 (3-chloro-4-fluorophenyl)(3,3-difluorocyclopentyl)(5-methyl-4-(methylsulfonyl)-1-((2-(trimethylsilyl)eth- oxy)methyl)-1H-imidazol-2-yl)methanol and the corresponding SEM regioisomer Step 1: To a stirred solution of 3,3-difluorocyclopentane-1-carboxylic acid (2.0 g, 13.322 mmol), N, O-dimethyl hydroxylamine (1.627 g, 26.644 mmol) and DIPEA (9.282 mL, 53.289 mmol) in DCM (20 mL) at 0 °C was added HATU (7.598 g, 19.983 mmol). The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was quenched with water (50 mL) and extracted with EtOAc (3 × 50 mL). The combined organic layers were washed with water (50 mL) and brine (50 mL) and were then concentrated under reduced pressure to afford the crude compound, which was purified by column chromatography (SiO2, 70% EtOAc / pet ether) afford 3,3- difluoro-N-methoxy-N-methylcyclopentane-1-carboxamide (2.1 g, 81%). Step 2: To a stirred solution of magnesium (0.67 g, 27.91 mmol) in THF (5.0 mL) at room temperature were added 4-bromo-2-chloro-1-fluorobenzene (3.398 mL, 27.907 mmol) and DIBAL-H (1.2M solution in toluene, 0.5 mL). The mixture was stirred for 1 h. The mixture was cooled to 0 °C and 3,3-difluoro-N-methoxycyclopentane-1- carboxamide (1.0 g, 5.58 mmol) in THF (25.0 mL) was added. The reaction mixture was stirred at room tempera- ture for 18 h. The reaction mixture was quenched with saturated ammonium chloride solution (20 mL) and ex- tracted with EtOAc (2 × 30 mL). The combined organic layers were washed with water (20 mL) and brine (20 mL) and were concentrated under reduced pressure to afford the crude compound, which was purified by column 48 GRA 4216-foreign filing chromatography (SiO2, 5% EtOAc / pet ether) to afford (3-chloro-4-fluorophenyl) (3,3-difluorocyclopentyl) meth- anone (0.9 g, 61%). Step 3: To a stirred solution of 4-iodo-5-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole (mixture of regioisomers, intermediate 27, 1.288 g, 3.807 mmol) in THF (15 mL) at -78°C was added LDA (2M in THF, 3.807 mL, 7.615 mmol). The reaction mixture was stirred at -78°C for 1 h, then (3-chloro-4-fluorophenyl) (3,3-difluo- rocyclopentyl) methanone (1.0 g, 3.807 mmol) in THF (5 mL) was added. The reaction mixture was stirred at -78 °C for 2 h. The reaction mixture was quenched with saturated ammonium chloride solution (50 mL) and extracted with EtOAc (2 × 50 mL). The combined organic layers were washed with water (30 mL) and brine solution (30 mL) and were concentrated under reduced pressure to afford the crude compound, which was purified by column chromatography (SiO2, 15% EtOAc / pet ether) and later reverse phase chromatography to afford (3-chloro-4-fluor- ophenyl)(3,3-difluorocyclopentyl)(4-iodo-5-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2- yl)methanol and the corresponding SEM regioisomer (0.8 g, 35%). Step 4: To a stirred degassed solution of (3-chloro-4-fluorophenyl)(3,3-difluorocyclopentyl)(4-iodo-5-methyl-1- ((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methanol (mixture of regioisomers, 0.9 g, 1.498 mmol), me- thanesulfinic acid sodium salt (0.612 g, 5.991 mmol, 4 equiv.), sodium hydroxide (0.120 g, 2.995 mmol) and L- Proline (0.172 g, 1.498 mmol) in DMSO (18 mL) at room temperature was added copper(I)iodide (0.143 g, 0.749 mmol). The reaction mixture was stirred at 80 °C for 18 h. The reaction mixture was diluted with 10% MeOH:DCM (50 mL), filtered through a celite bed, the filtrate was washed with water (2 × 30 mL) and brine (20 mL), dried over Na2SO4 and concentrated under the reduced pressure to afford the crude compound. The crude was purified by column chromatography (SiO2, 12% EtOAc / pet ether) to afford the title compounds (0.23 g, 27%). The title compound was prepared from the inermediates using an analogous method to that described for Interme- diate 47. Intermedi- Structure Name Data ate 48 (3-chloro-4-fluoro- LCMS m / z = 581 [M+H]+. phenyl)(chroman-3-yl)(5- methyl-4-(methylsulfonyl)- 1-((2-(trimethylsilyl)eth- oxy)methyl)-1H-imidazol-2- yl)methanol and the corre- sponding SEM regioisomer Intermediate 49 (3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2- yl)methyl diisopropylcarbamate and the corresponding SEM regioisomer 49 GRA 4216-foreign filing 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole (intermediate 27, mixture of regioisomers, 12 g, 35.475 mmol) in MeCN (50 mL) were added diisopropylcarbamic chloride (6.38 g, 39.023 mmol), 3-chloro-4-fluorobenzaldehyde (8.437 g, 53.213 mmol) and DIPEA (19.61 mL, 106.4 mmol) at room temperature. The resulting mixture was stirred at 80 °C for 16 h. The reaction mixture was diluted with water (150 mL) and extracted with ethyl acetate (2×150 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford the crude product, which was purified by col- umn chromatography (SiO2, 15-20% EtOAc / pet ether) to afford 15 g (68%) of (3-chloro-4-fluorophenyl)(4-iodo- 5-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methyl diisopropylcarbamate (mixture of regioi- somers). Step 2: A mixture of (3-chloro-4-fluorophenyl)(4-iodo-5-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imid- azol-2-yl)methyl diisopropylcarbamate (mixture of regioisomers, 7 g, 11.218 mmol), sodium methanesulfonate (5.299 g, 44.871 mmol), cesium carbonate (3.655 g, 11.218 mmol), L-proline (1.29 g, 11.21 mmol) and copper(I) iodide (1.71 g, 8.974 mmol) in DMSO (80 mL) was stirred at 120 °C for 16 h in a sealed tube. The reaction mixture was cooled to room temperature, diluted with water (100 mL) and extracted with EtOAc (3×100 mL). The com- bined organic layers were washed with brine (2×80 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford the crude product, which was purified by column chromatography (C18, MeCN / water) to afford 3.0 g of the title compounds. Example 1 2- methyl)-5-(methylsulfonyl)-1H-imidazole To a solution of 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-iodo-1H-imidazole (intermediate 4, 0.4 g, 0.86 mmol) in DMSO (10.0 mL) were added Cs2CO3 (0.7 g, 2.15 mmol), L-Proline (0.08 g, 0.688 mmol) and sodium me- thanesulfinate (0.132 g, 1.29 mmol) at rt. The reaction mixture was degassed with argon for 10 minutes followed by the addition of CuI (0.066 g, 0.344 mmol) at rt. The reaction mixture was heated to 110 °C for 2.5 h under microwave irradiation. The reaction mixture was diluted with water and extracted with ethyl acetate (2 x 50 mL). The combined organic layers were washed with brine, dried over sodium sulphate and concentrated under reduced pressure. The resulting crude product was purified by reverse-phase prep HPLC to yield the title compound (0.072 50 GRA 4216-foreign filing g, 20%). LCMS m / z = 417 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.89 (s, 1H), 7.85 (s, 1H), 7.54-7.52 (m, 2H), 7.42-7.38 (m, 2H), 7.33-7.30 (m, 2H), 5.74 (m, 1H), 3.10 (s, 3H). Examples 2-8. The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for example 1. Example Structure Name Data 2 2-(bis(3-chloro-4-fluoro- Yield: (0.035 g, 18%). phenyl)methyl)-5-(ethyl- LCMS m / z = 431 [M+H]+; sulfonyl)-1H-imidazole1H-NMR (400 MHz, DMSO-d6): 12.91 (s, 1H), 7.86 (s, 1H), 7.52-7.51 (m, 2H), 7.42-7.37 (m, 2H), 7.32-7.29 (m, 2H), 5.72 (s, 1H), 3.19-3.14 (m, 2H), 1.14-1.10 (m, 3H). 3 2-(bis(3-chloro-4-fluoro- Yield: (0.035 g, 10%). phenyl)methyl)-5-(cyclo- LCMS m / z = 443 [M+H]+; propylsulfonyl)-1H-imidaz-1H-NMR (400 MHz, ole DMSO-d6): 12.88 (bs, 1H), 7.82 (s, 1H), 7.56- 7.54 (m, 2H), 7.42-7.38 (m, 2H), 7.33-7.30 (m, 2H), 5.73 (s, 1H), 2.73- 2.69 (m, 1H), 1.06-3.05 (m, 2H), 1.03-0.98 (m, 2H). 4 2-(bis(3-chloro-4-fluoro- LCMS m / z = 445 [M+H]+; phenyl)methyl)-4-(iso- retention time: 7.67 min, propylsulfonyl)-1H-imidaz- method B ole 51 GRA 4216-foreign filing 5 2-(bis(3-chloro-4-fluorophe- LCMS m / z = 473 [M+H]+; nyl)methyl)-4-((tetrahydro- retention time: 2.96 min, furan-3-yl)sulfonyl)-1H- method A imidazole 6 2-(bis(3-chloro-4-fluorophe- LCMS m / z = 487 [M+H]+; nyl)methyl)-4-((tetrahydro- retention time: 3.00 min, 2H-pyran-4-yl)sulfonyl)- method A 1H-imidazole 7 2-((2-(bis(3-chloro-4-fluoro- LCMS m / z = 446 [M+H]+; phenyl)methyl)-1H-imida- retention time: 2.61 min, zol-4-yl)sulfonyl)ethan-1-a- method A mine 8 2-(bis(3-chloro-4-fluorophe- Yield: 82% (0.042 g, nyl)methyl)-5-chloro-4-(me- 0.093 mmol). LCMS m / z thylsulfonyl)-1H-imidazole = 451 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 7.37 (d, 2H), 7.21 (d, 4H), 5.54 (s, 1H), 3.18 (s, 3H). Example 9 2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole-5-sulfonamide 52 GRA 4216-foreign filing To a solution of 4-(benzylthio)-2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole (intermediate 6, 0.14 g, 0.304 mmol) in MeCN (8.0 mL)-AcOH (1.0 mL)-H2O (0.5 mL) was added DCDMH (0.12 g, 0.609 mmol) at 0 °C. The reaction was stirred at rt for 2 h. The reaction mixture was diluted with water (20.0 mL) and extracted with ethyl acetate (3 x 60 mL). The combined organic layers were washed with brine, dried over Na2SO4and concentrated under reduced pressure to obtain a residue, which was dissolved in THF (12.0 mL) and cooled to 0° C followed by the addition of 30% aq NH3(6.0 mL) at 0 °C. The resulting mixture was stirred at rt for 16 h. The reaction mixture was diluted with water (20 mL) and extracted with ethyl acetate (2 x 50 mL). The combined organic layers were washed with brine, dried over sodium sulphate and concentrated under reduced pressure to get the crude product which was purified by reverse-phase prep HPLC to yield the title compound (0.022 g, 16% over two steps). LCMS m / z = 418 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.75 (s, 1H), 7.57 (s, 1H), 7.52 (d, 2H), 7.42-7.38 (m, 2H), 7.38-7.28 (m, 2H), 7.17 (s, 2H), 5.17 (s, 1H). Example 10. The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for example 9. Ex- Structure Name Data anple 10 O 2-(bis(3-chloro-4-fluoro- Yield: (0.013 g, 10%). OS NH2phenyl)methyl)-4-methyl- LCMS m / z = 432 F HN 1H-imidazole-5-sulfona- [M+H]+;1H-NMR Cl N mide (400 MHz, DMSO- d6): 12.30 (s, 1H), 7.53-7.50 (m, 2H), Cl 7.42-7.37 (m, 2H), F 7.33-7.29 (m, 2H), 7.04 (s, 1H), 5.62 (s, 1H), 2.32 (s, 3H) 53 GRA 4216-foreign filing Example 11 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(1-(dimethylamino)propan-2-yl)-1H-imidazole-5-sulfonamide chloro-4-fluorophenyl)methyl)-4-((4-methoxybenzyl)thio)-1H-imidazole (0.6 g, 1.22 mmol) in MeCN (35.0 mL)-AcOH (4.0 mL)-H2O (2.0 mL) was added DCDMH (0.5 g, 2.53 mmol) at 0 °C. The reaction was stirred at rt for 2 h.The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (3 x 80 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure to get the crude product, which was purified by CombiFlash column chromatography (SiO2, 0-40% EtOAc / Hex) to afford 2-(bis(3-chloro-4-fluorophenyl) methyl)-1H-imidazole-4- sulfonyl chloride (0.35 g, 65%). Step 2: To a stirred solution of 2-(bis(3-chloro-4-fluorophenyl) methyl)-1H-imidazole-4-sulfonyl chloride (0.1 g, 0.23 mmol) in DCM (5.0 mL) was added TEA (2.5 equiv.) at 0 °C. To it was added N1,N1-dimethylpropane-1,2- diamine (0.9 eq) at 0 °C and the reaction mixture was stirred at rt for 1.5 hours. The volatiles were removed under reduced pressure and the residue was purified via reverse-phase prep. HPLC. LCMS m / z = 503 [M+H]+; retention time: 2.68 min, method A Examples 12-62, 148-184. The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for example 11. If applicable, a Boc protecting group was deprotected in the last step using procedures known to the person skilled in the art (e.g. TFA, DCM, 0 °C). If applicable, chiral SFC was perfomed to separate enantiomers. Ex- Structure Name Data anple 12 2-(bis(3-chloro-4- LCMS m / z = 515 [M+H]+; fluorophenyl)methyl)- retention time: 2.68 min, N-(2-(pyrrolidin-1- method A yl)ethyl)-1H-imidaz- ole-5-sulfonamide GRA 4216-foreign filing 1-((2-(bis(3-chloro-4- LCMS m / z = 529 [M+H]+; fluorophenyl)methyl)- retention time: 3.19 min, 1H-imidazol-5-yl)sul- method A fonyl)-4-isopropylpi- perazine 1-((2-(bis(3-chloro-4- LCMS m / z = 515 [M+H]+; fluorophenyl)methyl)- retention time: 3.06 min, 1H-imidazol-5-yl)sul- method A fonyl)-4-ethylpipera- zine 1-((2-(bis(3-chloro-4- LCMS m / z = 529 [M+H]+; fluorophenyl)methyl)- retention time: 5.65 min, 1H-imidazol-5-yl)sul- method A fonyl)-4-(methyl- sulfonyl)piperazine 2-(bis(3-chloro-4- LCMS m / z = 476 [M+H]+; fluorophenyl)methyl)- retention time: 2.85 min, N-(2-hydroxyethyl)- method A N-methyl-1H-imidaz- ole-5-sulfonamide 2-(bis(3-chloro-4- LCMS m / z = 476 [M+H]+; fluorophenyl)methyl)- retention time: 2.93 min, N-(2-methoxyethyl)- method A 1H-imidazole-5-sul- fonamide GRA 4216-foreign filing 2-(bis(3-chloro-4- LCMS m / z = 489 [M+H]+; fluorophenyl)methyl)- retention time: 2.67 min, N-(2-(dimethyla- method A mino)ethyl)-1H-imid- azole-5-sulfonamide 1-(4-((2-(bis(3-chloro- LCMS m / z = 529 [M+H]+; 4-fluorophenyl)me- retention time: 2.82 min, thyl)-1H-imidazol-5- method A yl)sulfonyl)piperazin- 1-yl)ethan-1-one 2-(bis(3-chloro-4- LCMS m / z = 476 [M+H]+; fluorophenyl)methyl)- retention time: 2.79 min, N-(2-hydroxypropyl)- method A 1H-imidazole-5-sul- fonamide (R)-2-(bis(3-chloro-4- LCMS m / z = 488 [M+H]+; fluorophenyl)methyl)- retention time: 2.93 min, N-(oxetan-2-ylme- method A thyl)-1H-imidazole-5- sulfonamide 1-((2-(bis(3-chloro-4- LCMS m / z = 501 [M+H]+; fluorophenyl)methyl)- retention time: 3.08 min, 1H-imidazol-5-yl)sul- method A fonyl)-N,N-dime- thylazetidin-3-amine GRA 4216-foreign filing 1-((2-(bis(3-chloro-4- LCMS m / z = 515 [M+H]+; fluorophenyl)methyl)- retention time: 3.02 min, 1H-imidazol-5-yl)sul- method A fonyl)-N,N-dime- thylpyrrolidin-3-amine 2-(bis(3-chloro-4- LCMS m / z = 524 [M+H]+; fluorophenyl)methyl)- retention time: 2.88 min, N-(2-(methyl- method A sulfonyl)ethyl)-1H- imidazole-5-sulfona- mide 2-(bis(3-chloro-4- LCMS m / z = 462 [M+H]+; fluorophenyl)methyl)- retention time: 2.76 min, N-(2-hydroxyethyl)- method A 1H-imidazole-5-sul- fonamide 2-(bis(3-chloro-4- LCMS m / z = 490 [M+H]+; fluorophenyl)methyl)- retention time: 2.86 min, N-(2-hydroxy-2- method A methylpropyl)-1H-im- idazole-5-sulfonamide 2-(bis(3-chloro-4- LCMS m / z = 490 [M+H]+; fluorophenyl)methyl)- retention time: 3.03 min, N-(1-methoxypropan- method A 2-yl)-1H-imidazole-5- sulfonamide GRA 4216-foreign filing 2-(bis(3-chloro-4- LCMS m / z = 538 [M+H]+; fluorophenyl)methyl)- retention time: 2.95 min, N-methyl-N-(2-(me- method A thylsulfonyl)ethyl)- 1H-imidazole-5-sul- fonamide 4-((2-(bis(3-chloro-4- LCMS m / z = 520 [M+H]+; fluorophenyl)methyl)- retention time: 2.79 min, 1H-imidazol-5-yl)sul- method A fonyl)thiomorpholine 1-oxide 2-(bis(3-chloro-4- LCMS m / z = 490 [M+H]+; fluorophenyl)methyl)- retention time: 2.98 min, N-(3-methoxypropyl)- method A 1H-imidazole-5-sul- fonamide 2-(bis(3-chloro-4- LCMS m / z = 488 [M+H]+; fluorophenyl)methyl)- retention time: 2.83 min, N-(oxetan-3-ylme- method A thyl)-1H-imidazole-5- sulfonamide 2-(bis(3-chloro-4- LCMS m / z = 503 [M+H]+; fluorophenyl)methyl)- retention time: 2.59 min, N-(3-(dimethyla- method A mino)propyl)-1H-im- idazole-5-sulfonamide GRA 4216-foreign filing 1-((2-(bis(3-chloro-4- LCMS m / z = 529 [M+H]+; fluorophenyl)methyl)- retention time: 2.69 min, 1H-imidazol-5-yl)sul- method A fonyl)-N,N-dime- thylpiperidin-4-amine ethyl ((2-(bis(3- LCMS m / z = 504 [M+H]+; chloro-4-fluoro- retention time: 2.98 min, phenyl)methyl)-1H- method A imidazol-5-yl)sul- fonyl)glycinate 2-(bis(3-chloro-4- LCMS m / z = 522 [M+H]+; fluorophenyl)methyl)- retention time: 2.97 min, N-(1,1-dioxidothietan- method A 3-yl)-1H-imidazole-5- sulfonamide 2-(bis(3-chloro-4- LCMS m / z = 518 [M+H]+; fluorophenyl)methyl)- retention time: 2.83 min, N-((3R,4R)-4-hydrox- method A ytetrahydro-2H-pyran- 3-yl)-1H-imidazole-5- sulfonamide GRA 4216-foreign filing 2-(bis(3-chloro-4- LCMS m / z = 550 [M+H]+; fluorophenyl)methyl)- retention time: 2.94 min, N-(1,1-dioxidotetrahy- method A drothiophen-3-yl)-N- methyl-1H-imidazole- 5-sulfonamide 1-((2-(bis(3-chloro-4- LCMS m / z = 474 [M+H]+; fluorophenyl)methyl)- retention time: 2.85 min, 1H-imidazol-5-yl)sul- method A fonyl)azetidin-3-ol (R)-2-(bis(3-chloro-4- LCMS m / z = 520 [M+H]+; fluorophenyl)methyl)- retention time: 2.98 min, N-(2,3-dimethoxypro- method A pyl)-1H-imidazole-5- sulfonamide 2-(bis(3-chloro-4- LCMS m / z = 474 [M+H]+; fluorophenyl)methyl)- retention time: 2.82 min, N-(oxetan-3-yl)-1H- method A imidazole-5-sulfona- mide

[0002] GRA 4216-foreign filing 1-((2-(bis(3-chloro-4- LCMS m / z = 487 [M+H]+; fluorophenyl)methyl)- retention time: 2.71 min, 1H-imidazol-5-yl)sul- method A fonyl)piperazine tert-butyl 3-((2-(bis(3- LCMS m / z = 601 [M+H]+; chloro-4-fluoro- retention time: 3.26 min, phenyl)methyl)-1H- method A imidazole)-5-sulfon- amido)piperidine-1- carboxylate N-(2-((2-(bis(3- LCMS m / z = 503 [M+H]+; chloro-4-fluoro- retention time: 2.70 min, phenyl)methyl)-1H- method A imidazole)-5-sulfon- amido)ethyl)acetamide N-(1-((2-(bis(3- LCMS m / z = 515 [M+H]+; chloro-4-fluoro- retention time: 2.79 min, phenyl)methyl)-1H- method A imidazol-5-yl)sul- fonyl)azetidin-3-yl)ac- etamide 2-((2-(bis(3-chloro-4- LCMS m / z = 503 [M+H]+; fluorophenyl)methyl)- retention time: 2.93 min, N-methyl-1H-imidaz- method A ole)-5-sulfonamido)- N-methylacetamide GRA 4216-foreign filing 2-(bis(3-chloro-4- LCMS m / z = 502 [M+H]+; fluorophenyl)methyl)- retention time: 2.88 min, N-(3-methoxycyclobu- method A tyl)-1H-imidazole-5- sulfonamide 2-(bis(3-chloro-4- LCMS m / z = 502 [M+H]+; fluorophenyl)methyl)- retention time: 2.71 min, N-(3-hydroxycyclo- method A pentyl)-1H-imidazole- 5-sulfonamide N-(1-acetylpiperidin- LCMS m / z = 543 [M+H]+; 4-yl)-2-(bis(3-chloro- retention time: 2.76 min, 4-fluorophenyl)me- method A thyl)-1H-imidazole-5- sulfonamide 2-(bis(3-chloro-4- LCMS m / z = 482 [M+H]+; fluorophenyl)methyl)- retention time: 3.03 min, N-(2,2-difluoroethyl)- method A 1H-imidazole-5-sul- fonamide GRA 4216-foreign filing 3-((2-(bis(3-chloro-4- LCMS m / z = 517 [M+H]+; fluorophenyl)methyl)- retention time: 2.77 min, 1H-imidazole)-5-sul- method A fonamido)-2,2-dime- thylpropanamide 2-(bis(3-chloro-4- LCMS m / z = 515 [M+H]+; fluorophenyl)methyl)- retention time: 2.59 min, N-(1-methylpiperidin- method A 4-yl)-1H-imidazole-5- sulfonamide methyl ((2-(bis(3- LCMS m / z = 490 [M+H]+; chloro-4-fluoro- retention time: 2.95 min, phenyl)methyl)-1H- method A imidazol-5-yl)sul- fonyl)glycinate 2-((2-(bis(3-chloro-4- LCMS m / z = 489 [M+H]+; fluorophenyl)methyl)- retention time: 2.75 min, 1H-imidazole)-5-sul- method A fonamido)propana- mide

[0003] GRA 4216-foreign filing 2-(bis(3-chloro-4- LCMS m / z = 457 [M+H]+; fluorophenyl)methyl)- retention time: 3.01 min, N-(cyanomethyl)-1H- method A imidazole-5-sulfona- mide 2-(bis(3-chloro-4- LCMS m / z = 489 [M+H]+; fluorophenyl)methyl)- retention time: 2.71 min, N-methyl-N-(2-(me- method A thylamino)ethyl)-1H- imidazole-5-sulfona- mide (R)-1-((2-(bis(3- LCMS m / z = 501 [M+H]+; chloro-4-fluoro- retention time: 2.78 min, phenyl)methyl)-1H- method A imidazol-5-yl)sul- fonyl)-3-methylpipera- zine 1-((2-(bis(3-chloro-4- LCMS m / z = 501 [M+H]+; fluorophenyl)methyl)- retention time: 2.71 min, 1H-imidazol-5-yl)sul- method A fonyl)-N-methylpyr- rolidin-3-amine 2-((2-(bis(3-chloro-4- LCMS m / z = 499 [M+H]+; fluorophenyl)methyl)- retention time: 2.57 min, 1H-imidazol-5-yl)sul- method A fonyl)-2,6-dia- zaspiro[3.3]heptane 64 GRA 4216-foreign filing 2-(bis(3-chloro-4- LCMS m / z = 501 [M+H]+; fluorophenyl)methyl)- retention time: 2.57 min, N-(piperidin-3-yl)-1H- method A imidazole-5-sulfona- mide 2-((2-(bis(3-chloro-4- LCMS m / z = 489 [M+H]+; fluorophenyl)methyl)- retention time: 2.77 min, N-methyl-1H-imidaz- method A ole)-5-sulfon- amido)acetamide a (S)-1-((2-(bis(3- LCMS m / z = 501 [M+H]+; chloro-4-fluoro- retention time: 2.79 min, phenyl)methyl)-1H- method A imidazol-5-yl)sul- fonyl)-3-methylpipera- zine 2-((2-(bis(3-chloro-4- LCMS m / z = 499 [M+H]+; fluorophenyl)methyl)- retention time: 2.62 min, 1H-imidazol-5-yl)sul- method A fonyl)-2,5-diazabicy- clo[2.2.1]heptane 1-((2-(bis(3-chloro-4- LCMS m / z = 501 [M+H]+; fluorophenyl)methyl)- retention time: 2.70 min, 1H-imidazol-5-yl)sul- method A fonyl)piperidin-3- amine 65 GRA 4216-foreign filing (1-((2-(bis(3-chloro-4- LCMS m / z = 487 [M+H]+; fluorophenyl)methyl)- retention time: 2.58 min, 1H-imidazol-5-yl)sul- method A fonyl)azetidin-3- yl)methanamine ((2-(bis(3-chloro-4- LCMS m / z = 476 [M+H]+; fluorophenyl)methyl)- retention time: 2.43 min, 1H-imidazol-5-yl)sul- method A fonyl)glycine a 2-(bis(3-chloro-4- LCMS m / z = 504 [M+H]+; fluorophenyl)methyl)- retention time: 2.63 min, N-((3R,4S)-4-hydrox- method A ytetrahydrofuran-3- yl)-1H-imidazole-5- sulfonamide a (3S,5R)-1-((2-(bis(3- LCMS m / z = 515 [M+H]+; chloro-4-fluoro- retention time: 2.72 min, phenyl)methyl)-1H- method A imidazol-5-yl)sul- fonyl)-3,5-dimethylpi- perazine 66 GRA 4216-foreign filing N-(azetidin-3-ylme- LCMS m / z = 487 [M+H]+; thyl)-2-(bis(3-chloro- retention time: 2.39 min, 4-fluorophenyl)me- method A thyl)-1H-imidazole-5- sulfonamide a (S)-1-((2-(bis(3- LCMS m / z = 501 [M+H]+; chloro-4-fluoro- retention time: 2.59 min, phenyl)methyl)-1H- method A imidazol-5-yl)sul- fonyl)-2-methylpipera- zine a (R)-2-(bis(3-chloro-4- LCMS m / z = 487 [M+H]+; fluorophenyl)methyl)- retention time: 2.33 min, N-(pyrrolidin-3-yl)- method A 1H-imidazole-5-sul- fonamide b (S)-2-(bis(3-chloro-4- LCMS m / z = 487 [M+H]+; fluorophenyl)methyl)- retention time: 2.42 min, N-(pyrrolidin-3-yl)- method A 1H-imidazole-5-sulfo- namide 67 GRA 4216-foreign filing N-(azetidin-3-yl)-2- LCMS m / z = 473 [M+H]+; (bis(3-chloro-4-fluoro- retention time: 2.37 min, phenyl)methyl)-1H- method A imidazole-5-sulfona- mide a (R)-2-(bis(3-chloro-4- LCMS m / z = 501 [M+H]+; fluorophenyl)methyl)- retention time: 2.42 min, N-(pyrrolidin-3-ylme- method A thyl)-1H-imidazole-5- sulfonamide a N-((cis)-3-aminocy- LCMS m / z = 487 [M+H]+; clobutyl)-2-(bis(3- retention time: 2.39 min, chloro-4-fluoro- method A phenyl)methyl)-1H- imidazole-5-sulfona- mide bNH2N-((trans)-3-aminocy- LCMS m / z = 487 [M+H]+; clobutyl)-2-(bis(3- retention time: 2.40 min, O O chloro-4-fluoro- method A SNHF phenyl)methyl)-1H- HN imidazole-5-sulfona- Cl N mide Cl F 68 GRA 4216-foreign filing 2-(bis(3-chloro-4-flu- LCMS m / z = 490 [M+H]+; orophenyl)methyl)-N- retention time: 2.77 min, (1-hydroxy-2-methyl- method A propan-2-yl)-1H- imidazole-5-sulfona- mide a N-((1S,3S)-3-ami- LCMS m / z = 501 [M+H]+; nocyclopentyl)-2- retention time: 2.39 min, (bis(3-chloro-4-fluoro- method A phenyl)methyl)-1H- imidazole-5-sulfona- mide 1-((2-(bis(3-chloro-4- LCMS m / z = 487 [M+H]+; fluorophenyl)methyl)- retention time: 2.68 min, 1H-imidazol-5-yl)sul- method A fonyl)-N-methylazeti- din-3-amine 2-(bis(3-chloro-4-flu- LCMS m / z = 489 [M+H]+; orophenyl)methyl)-N- retention time: 2.40 min, (3-(methylamino)pro- method A pyl)-1H-imidazole-5- sulfonamide

[0004] GRA 4216-foreign filing N-(3-aminopropyl)-2- LCMS m / z = 489 [M+H]+; (bis(3-chloro-4-fluoro- retention time: 2.46 min, phenyl)methyl)-N-me- method A thyl-1H-imidazole-5- sulfonamide 2-(bis(3-chloro-4-flu- LCMS m / z = 475 [M+H]+; orophenyl)methyl)-N- retention time: 4.92 min, (2-(methyla- method B mino)ethyl)-1H-imida- zole-5-sulfonamide 1-((2-(bis(3-chloro-4- LCMS m / z = 501 [M+H]+; fluorophenyl)methyl)- retention time: 2.44 min, 1H-imidazol-5-yl)sul- method A fonyl)piperidin-4-a- mine 2-(bis(3-chloro-4-flu- LCMS m / z = 490 [M+H]+; orophenyl)methyl)-N- retention time: 3.02 min, (2-methoxypropyl)- method A 1H-imidazole-5-sulfo- namide

[0005] GRA 4216-foreign filing N-(2-amino-2-methyl- LCMS m / z = 489 [M+H]+; propyl)-2-(bis(3- retention time: 2.44 min, chloro-4-fluorophe- method A nyl)methyl)-1H-imida- zole-5-sulfonamide 2-(bis(3-chloro-4-flu- LCMS m / z = 446 [M+H]+; orophenyl)methyl)- retention time: 7.73 min, N,N-dimethyl-1H- method B imidazole-5-sulfona- mide 2-(bis(3-chloro-4-flu- LCMS m / z = 458 [M+H]+; orophenyl)methyl)-N- retention time: 7.58 min, cyclopropyl-1H- method B imidazole-5-sulfona- mide 2-(bis(3-chloro-4-flu- LCMS m / z = 472 [M+H]+; orophenyl)methyl)-5- retention time: 7.77 min, (pyrrolidin-1-ylsul- method B fonyl)-1H-imidazole 2-(bis(3-chloro-4-flu- LCMS m / z = 507 [M+H]+; orophenyl)methyl)-5- retention time: 7.81 min, ((3,3-difluoropyrroli- method B din-1-yl)sulfonyl)-1H- imidazole 71 GRA 4216-foreign filing a 2-(bis(3-chloro-4- LCMS m / z = 516 [M+H]+; fluorophenyl)methyl)- retention time: 3.22 min, 5-((3-methoxy-3- method A, Chiral SFC: col- methylpyrrolidin-1- umn: Chiralpak IC (4.6 x yl)sulfonyl)-1H-imid- 250 mm) 5 m; co-solvent: azole 0.3% iPrNH2in MeOH, flow: 4 mL / min; % of co-sol- vent: 45%; ABPR: 100 bar T: 35 °C; Rt = 2.58 min (first eluting). b 2-(bis(3-chloro-4- LCMS m / z = 516 [M+H]+; fluorophenyl)methyl)- retention time: 3.22 min, 5-((3-methoxy-3- method A, Chiral SFC: col- methylpyrrolidin-1- umn: Chiralpak IC (4.6 x yl)sulfonyl)-1H-imid- 250 mm) 5 m; co-solvent: azole 0.3% iPrNH2 in MeOH, flow: 4 mL / min; % of co-sol- vent: 45%; ABPR: 100 bar T: 35 °C; Rt = 2.89 min (first eluting). 4-((2-(bis(3-chloro-4- LCMS m / z = 501 [M+H]+; fluorophenyl)methyl)- retention time: 7.19 min, 1H-imidazol-5-yl)sul- method B fonyl)piperazin-2-one O 2-(bis(3-chloro-4- LCMS m / z = 499 [M+H]+; fluorophenyl)methyl)- retention time: 2.70 min, NH O N-(5-oxopyrrolidin-3- method A OS NHyl)-1H-imidazole-5- F HN sulfonamide Cl N Cl F 72 GRA 4216-foreign filing a (R)-1-((2-(bis(3- LCMS m / z = 488 [M+H]+; chloro-4-fluoro- retention time: 2.91 min, phenyl)methyl)-1H- method A imidazol-5-yl)sul- fonyl)pyrrolidin-3-ol b (S)-1-((2-(bis(3- LCMS m / z = 488 [M+H]+; chloro-4-fluoro- retention time: 2.91 min, phenyl)methyl)-1H- method A imidazol-5-yl)sul- fonyl)pyrrolidin-3-ol 2-((2-(bis(3-chloro-4- LCMS m / z = 475 [M+H]+; fluorophenyl)methyl)- retention time: 2.68 min, 1H-imidazole)-5-sul- method A fonamido)acetamide a (R)-2-(bis(3-chloro-4- LCMS m / z = 488 [M+H]+; fluorophenyl)methyl)- retention time: 7.44 min, N-(tetrahydrofuran-3- method B yl)-1H-imidazole-5- sulfonamide

[0006] 73 GRA 4216-foreign filing 180b (S)-2-(bis(3-chloro-4- LCMS m / z = 488 [M+H]+; fluorophenyl)methyl)- retention time: 2.95 min, N-(tetrahydrofuran-3- method A yl)-1H-imidazole-5- sulfonamide Example 76 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(methylsulfinyl)-1H-imidazole To a stirred solution of 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-(methylthio)-1H-imidazole (intermediate 8, 0.22 g, 0.581 mmol) in DCM (5 ml) was added mCPBA (77% in water, 0.098 g, 0.436 mmol) at 0 °C. The reaction mixture was stirred for 20 minutes at 0 °C. The reaction mixture was diluted with water and extracted with EtOAc (3 × 60 mL). The combined organic part was washed with saturated NaHCO3solution and brine and was dried over Na2SO4. The organic layer was concentrated under reduced pressure to get the crude product, which was purified via column chromatography (SiO2, 0-60% EtOAc / Hex) followed by chiral HPLC to yield the title com- pound.Peak 1, example 76a: Yield: 19%, LCMS m / z = 401 [M+H]+; 1H-NMR (400 MHz, DMSO-d6): 12.62 (s, 1H),7.73 (s, 1H), 7.54 (bs, 2H), 7.41-7.34 (m, 4H), 5.72 (s, 1H), 2.80 (s, 3H). Chiral HPLC: column: Chiralpak IC (4.6 x 250 mm) 5 m, mobile phase: Hexane / DCM / EtOH / isopropylamine 50 / 25 / 25 / 0.1, flow rate: 1.0 mL / min, Rt = 4.63 min (first eluting).Peak 2, example 76b: Yield: 19%, LCMS m / z = 401 [M+H]+; 1H-NMR (400 MHz, DMSO-d6): 12.62 (s, 1H),7.73 (s, 1H), 7.54 (bs, 2H), 7.41-7.34 (m, 4H), 5.72 (s, 1H), 2.80 (s, 3H). Chiral HPLC: column: Chiralpak IC (4.6 x 250 mm) 5 m, mobile phase: Hexane / DCM / EtOH / isopropylamine 50 / 25 / 25 / 0.1, flow rate: 1.0 mL / min, Rt = 5.61 min (first eluting). Example 77 74 GRA 4216-foreign filing 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-methyl-5-(methylsulfinyl)-1H-imidazole To 19, 0.35 g, 0.877 mmol) in DCM (20.0 mL) was added mCPBA (70% in water; 0.148 g, 0.658 mmol) at 0 °C. The reaction mixture was stirred at 0 °C for 2 h. The reaction mixture was quenched with a (1:1) solution of sodium sulfite and sodium bicarbonate at 0 °C. The aqueous layer was extracted with ethyl acetate (2 × 100 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure to get the crude product. The resulting crude mixture was purified by CombiFlash column chromatography (SiO2, 0- 70% acetone / Hex) to yield the racemic title compound (0.25 g, 68%), which was separated using chiral SFC. Peak 1, example 77a: Yield: 14% (0.03 g, 0.072 mmol). LCMS m / z = 415 [M+H]+;1H-NMR (400 MHz, DMSO- d6): 12.39 (s, 1H), 7.57-7.53 (m, 2H), 7.42-7.34 (m, 4H), 5.65 (s, 1H), 2.78 (s, 3H), 2.29 (s, 3H). Chiral SFC: column: Chiralpak IC (4.6 x 250 mm) 5 m; co-solvent: 0.3% iPrNH2in isopropylalcohol, flow: 3 mL / min; % of co-solvent: 30%; ABPR: 1500 psi T: 35 °C; Rt = 5.35 min (first eluting). Peak 2, example 77b: Yield: 19% (0.04 g, 0.096 mmol). LCMS m / z = 415 [M+H]+;1H-NMR (400 MHz, DMSO- d6): 12.38 (s, 1H), 7.57-7.53 (m, 2H), 7.42-7.34 (m, 4H), 5.65 (s, 1H), 2.78 (s, 3H), 2.29 (s, 3H). Chiral SFC: column: Chiralpak IC (4.6 x 250 mm) 5 m; co-solvent: 0.3% iPrNH2in isopropylalcohol, flow: 3 mL / min; % of co-solvent: 30%; ABPR: 1500 psi T: 35 °C; Rt = 5.91 min (second eluting). Example 78 (2- 5-yl)(imino)(methyl)-l6-sulfanone and Step 1: Iodobenzene diacetate (0.39 g, 1.205 mmol) was added to a stirred suspension of 2-[bis(3-chloro-4-fluo- rophenyl)methyl]-4-methanesulfinyl-5-methyl-1H-imidazole (example 77, 0.25 g, 0.602 mmol), magnesium oxide (0.105 g, 2.59 mmol), rhodium(II) acetate dimer (0.027g, 0.06 mmol) and 2,2,2-trifluoro acetamide (0.15 g, 1.325 mmol) in dioxane (10.0 mL) at 40 °C. The reaction mixture was stirred at 40 °C for 6 h. The reaction mixture was 75 GRA 4216-foreign filing concentrated under reduced pressure to get the crude product which was purified by CombiFlash column chroma- tography (SiO2, 0-60% EtOAc / Hex) to yield N-((2-(bis(3-chloro-4-fluorophenyl)methyl)-5-methyl-1H-imidazol- 4-yl)(methyl)(oxo)-l6-sulfaneylidene)-2,2,2-trifluoroacetamide (0.12 g, 37%). LCMS m / z = 526 [M+H]+.Step 2: To a stirred solution of N-((2-(bis(3-chloro-4-fluorophenyl)methyl)-5-methyl-1H-imidazol-4-yl)(me-thyl)(oxo)-l6-sulfaneylidene)-2,2,2-trifluoroacetamide (0.12 g, 0.229 mmol) in acetonitrile:methanol (1:1) (4.0 mL) was added K2CO3(0.065 g, 0.457 mmol) at rt. The reaction mixture was stirred at rt for 6 h. The solvent was evaporated to get the crude product, which was purified by reverse-phase prep HPLC followed by the chiral sep- aration using chiral SFC to yield the title compound. Peak 1, example 78a: Yield: 35% (0.035 g, 0.081 mmol). LCMS m / z = 430 [M+H]+;1H-NMR (400 MHz, DMSO- d6): 12.79 (s, 1H), 7.55-7.53 (m, 2H), 7.43-7.38 (m, 2H), 7.34-7.33 (m, 2H), 5.68 (s, 1H), 3.29 (s, 3H, masked with water peak), 2.39 (s, 3H). Chiral SFC: column: Chiralpak IC (4.6 x 250 mm) 5 m; co-solvent: 0.3% iPrNH2 in isopropylalcohol, flow: 3 mL / min; % of co-solvent: 30%; ABPR: 1500 psi T: 35 °C; Rt = 2.26 min (first eluting). Peak 2, example 78b: Yield: 25% (0.035 g, 0.081 mmol). LCMS m / z = 430 [M+H]+;1H-NMR (400 MHz, DMSO- d6): 12.54 (s, 1H), 7.55-7.52 (m, 2H), 7.42-7.38 (m, 2H), 7.34-7.31 (m, 2H), 5.65 (s, 1H), 3.10 (s, 3H), 2.38 (s, 3H). Chiral SFC: column: Chiralpak IC (4.6 x 250 mm) 5 m; co-solvent: 0.3% iPrNH2in isopropylalcohol,, flow: 3 mL / min; % of co-solvent: 30%; ABPR: 1500 psi T: 35 °C; Rt = 2.89 min (second eluting). Example 79 2-(bis(3-chloro-4- methyl)-4-methyl-5-(methylsulfonyl)-1H-imidazole To a solution of 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-iodo-5-(methylsulfonyl)-1H-imidazole (intermediate 13, 0.125 g, 0.23 mmol) in 1,4-dioxane (7.0 mL) was added Cs2CO3 (0.151 g, 0.46 mmol) at rt. The reaction mixture was degassed with argon for 10 min followed by the addition of trimethylboroxine (0.06 g, 0.46 mmol)and PdCl2(dppf) DCM (0.01 g, 0.012 mmol) at rt. The reaction mixture was heated to 100 °C for 16 h in a sealedtube. The reaction mixture was filtered through a celite bed and the filtrate was concentrated under reduced pres- sure to get the crude product, which was purified by reverse-phase prep HPLC to the title compound (0.035 g, 35%). LCMS m / z = 431 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.58 (s, 1H), 7.54-7.52 (m, 2H), 7.42-7.37 (m, 2H), 7.33-7.30 (m, 2H), 5.65 (s, 1H), 3.06 (s, 3H), 2.36 (s, 3H). Example 80 The title compound wase prepared from the appropriate intermediates and reagents using an analogous method to that described for example 79. 76 GRA 4216-foreign filing Example Name / Structure / Data 80 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-cyclopropyl-5-(methylsulfonyl)-1H-imidazole Yield: 0.05 g, 34%. LCMS m / z = 457 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.18 (bs, 1H), 7.54-7.53 (m, 2H), 7.41-7.36 (m, 2H), 7.33-7.30 (m, 2H), 5.53 (s, 1H), 3.11 (s, 3H), 2.50-2.47 (m, 1H), 1.01-0.99 (m, 2H), 0.83-0.79 (m, 2H). Example 81 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(methylsulfonyl)-4-(trifluoromethyl)-1H-imidazole To a solution of 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-iodo-4-(methylsulfonyl)-1H-imidazole (intermediate 13, 0.5 g, 0.923 mmol) in NMP (3.0 mL) were added KF (0.27 g, 4.61 mmol) and CuI (0.36 g, 1.84 mmol) at rt. The reaction mixture was degassed with argon for 10 min followed by the dropwise addition of TMSCF3(3.0 mL, 18.45 mmol) at 0 °C over 2 minutes. The reaction mixture was heated to 110 °C in a sealed tube for 16 h. The reaction mixture was cooled to rt and was diluted with cold water (20 mL). The aqueous layer was extracted with ethyl acetate (2 × 80 mL). The combined organic layers were washed with brine, dried over Na2SO4and concen- trated under reduced pressure to get the crude product which was purified by RP prep HPLC to yield the title compound (0.07 g, 19%). LCMS m / z = 485 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 7.58-7.57 (m, 2H), 7.43- 7.39 (m, 2H), 7.34-7.33 (m, 2H), 5.75 (s, 1H), 3.22 (s, 3H, masked with water peak). Example 82 (2- (methyl)-l6-sulfanone and 77 GRA 4216-foreign filing Step 1: A mixture of 2-(bis(3-chloro-4-fluorophenyl) methyl)-5-iodo-1-((2-(trimethylsilyl) ethoxy) methyl)-1H- imidazole and 2-(bis(3-chloro-4-fluorophenyl) methyl)-4-iodo-1-((2-(trimethylsilyl) ethoxy) methyl)-1H-imidaz- ole (intermediate 5, 0.35 g, 0.58 mmol) in NMP (3 mL) was degassed with argon for 15 min followed by the addition of NaSMe (0.08 g, 1.17 mmol) and CuCl2(0.04 g, 0.29 mmol) at rt. The reaction mixture was heated to 130 °C for 16 h. The reaction mixture was cooled to rt and filtered through a celite bed. The filtrate was concen- trated under reduced pressure to get the crude product, which was purified by column chromatography (silica gel; 0-60% ethyl acetate in hexane as eluent) to afford a mixture of 2-(bis(3-chloro-4-fluorophenyl) methyl)-5-(me- thylthio)-1-((2-(trimethylsilyl) ethoxy) methyl)-1H-imidazole and 2-(bis(3-chloro-4-fluorophenyl) methyl)-4- (methylthio)-1-((2-(trimethylsilyl) ethoxy) methyl)-1H-imidazole (0.23 g, 77%). LCMS m / z = 515 [M+H]+. Step 2: To a mixture of 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(methylthio)-1-((2-(trimethylsilyl)ethoxy)me- thyl)-1H-imidazole and 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-(methylthio)-1-((2-(trimethylsilyl)ethoxy)me- thyl)-1H-imidazole (0.13 g, 0.25 mmol) in MeOH (4 mL) were added diacetoxyiodobenzene (0.65 g, 2.01 mmol) and ammonium carbonate (0.19 g, 2.01 mmol) at rt. The reaction mixture was stirred at rt for 2 h. The reaction mixture was diluted with water and extracted with EtOAc (3×100 mL). The combined organic part was washed with cold brine, dried over Na2SO4and concentrated under reduced pressure to get the crude product, which was purified by column chromatography (SiO2, 0-60% EtOAc / Hex) to afford a mixture of (2-(bis(3-chloro-4-fluoro- phenyl)methyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)(imino)(methyl)-l6-sulfanone and (2- (bis(3-chloro-4-fluorophenyl)methyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)(imino)(methyl)- l6-sulfanone (0.07 g, 51%). LCMS m / z = 546 [M+H]+. Step 3: To a mixture of (2-(bis(3-chloro-4-fluorophenyl)methyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imid- azol-5-yl)(imino)(methyl)-l6-sulfanone and (2-(bis(3-chloro-4-fluorophenyl)methyl)-1-((2-(trimethylsilyl)eth- oxy)methyl)-1H-imidazol-4-yl)(imino)(methyl)-l6-sulfanone (0.18 g, 0.33 mmol, 1.0 eq.) in EtOH (5 mL) was added 4(M) HCl in 1,4-dioxane (5 mL) at 0 °C. The reaction mixture was heated to 60 °C for 3 h. The reaction mixture was concentrated under reduced pressure to get the crude title compound, which was purified by reverse-phase prep HPLC followed by chiral separation to yield the separated enantiomers. Peak 1, example 82a: Yield: 0.025 g, 18%. LCMS m / z = 416 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.66 (brs, 1H), 7.65 (s, 1H), 7.53 (d, 2H), 7.40 (t, 2H), 7.34-7.31 (m, 2H), 5.71 (s, 1H), 3.96 (s, 1H), 3.00 (s, 3H). Chiral HPLC: column: Chiralpak IC (4.6 x 250 mm) 5 m, mobile phase: Hexane / DCM / EtOH / isopropylamine 50 / 25 / 25 / 0.1, flow rate: 1.0 mL / min Rt = 5.31 min (first eluting). Peak 2, example 82b: Yield: 0.025 g, 18%. LCMS m / z = 416 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.65 (brs, 1H), 7.66 (s, 1H), 7.53 (d, 2H), 7.40 (t, 2H), 7.34-7.31 (m, 2H), 5.72 (s, 1H), 3.96 (s, 1H), 3.00 (s, 3H). Chiral HPLC: column: Chiralpak IC (4.6 x 250 mm) 5 m, mobile phase: Hexane / DCM / EtOH / isopropylamine 50 / 25 / 25 / 0.1, flow rate: 1.0 mL / min Rt = 6.51 min (second eluting). 78 GRA 4216-foreign filing Example 87 (2-(bis(3-chloro-4-fluorophenyl)methyl)-4-(methylsulfonyl)-1H-imidazol-5-yl)methanol chloro-4-fluorophenyl)methyl]-4-iodo-5-methanesulfonyl-1H-imidazole (inter- mediate 13, 0.5 g, 0.92 mmol) in 1,4-dioxane-H2O (20.0 mL) were added K2CO3(0.153 g, 1.1 mmol) and potas- sium vinyltrifluoroborate (0.25 g, 1.84 mmol) at rt. The reaction mixture was degassed with argon for 10 minutes.PdCl2(dppf) DCM (0.034 g, 0.046 mmol) was added to the reaction mixture at rt. The reaction mixture was heatedto 110 °C for 16 h in a sealed tube. The reaction mixture was cooled to rt and filtered through a celite bed. The filtrate was evaporated under reduced pressure at low temperature to get the crude product, which was purified by CombiFlash column chromatography (SiO2, 0-70% EtOAc / Hex) to yield 2-(bis(3-chloro-4-fluorophenyl)methyl)- 4-(methylsulfonyl)-5-vinyl-1H-imidazole (0.35 g, 80%). LCMS m / z = 443 [M+H]+. Step2: To a stirred solution of 2-[bis(3-chloro-4-fluorophenyl)methyl]-5-ethenyl-4-methanesulfonyl-1H-imidaz- ole (0.35 g, 0.79 mmol) in 1,4-dioxane (10.0 mL) and H2O (3.0 mL) were added OsO4(0.16 M in H2O; 0.15 mL, 0.024 mmol) and NMO (50%; 0.102 g, 0.869 mmol) at rt. The reaction mixture was stirred at rt for 16 h. Then, NaIO4 (1.7 g ,7.90 mmol) was added at rt and the mixture was stirred for one hour. The reaction mixture was diluted with water (30.0 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried over anhyd. Na2SO4and concentrated under reduced pressure to get the crude product, which was purified by CombiFlash (SiO2, 0-20% EtOAc / Hex) to obtain 2-[bis(3-chloro-4-fluorophenyl)methyl]- 4-methanesulfonyl-1H-imidazole-5-carbaldehyde (0.12 g, 34%). Step 3: To a stirred solution of 2-[bis(3-chloro-4-fluorophenyl)methyl]-4-methanesulfonyl-1H-imidazole-5- carbaldehyde (0.1 g, 0.225 mmol) in MeOH (8.0 mL) was added portionwise NaBH4(0.07 g, 1.12 mmol) at 0 °C and the reaction mixture was stirred at rt for 2 h. The reaction mixture was cooled to 0 °C and diluted with water. The aqueous part was extracted with ethyl acetate (2 × 30 mL). The combined organic part was dried over anhy- drous Na2SO4 and concentrated under reduced pressure to get the crude product, which was purified by reverse- phase prep HPLC to get the title compound (0.045 g, 44%). LCMS m / z = 447 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.91 (s, 1H), 7.55-7.54 (m, 2H), 7.42-7.32 (m, 4H), 5.69 (s, 1H), 5.46-5.43 (m, 1H), 4.68-4.67 (m, 2 H), 3.09 (s, 3H). 79 GRA 4216-foreign filing Example 88 5-((3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-1H-imidazol-2-yl)methyl)-2-(2,2,2-trifluoroethoxy)pyridine Step 1: (3-Chloro-4-fluorophenyl)(4-(methylsulfonyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2- yl)methanone (intermediate 25, mixture of regioisomers, 200 mg, 0.463 mmol) was dissolved in 4 M HCl in 1,4- dioxane (5 mL) at rt and the mixture was stirred for 4 h. The mixture was concentrated under reduced pressure and the residue were taken up in ethyl acetate (20 mL) and washed with sodium bicarbonate solution (5 mL × 2). The combined organic layers were concentrated under reduced pressure to get crude (3-chloro-4-fluorophenyl)(4-(me- thylsulfonyl)-1H-imidazol-2-yl)methanone (0.13 g, crude) which was used in the next step without any further purification. Step 2: 5-Bromo-2-(2,2,2-trifluoroethoxy)pyridine (1271.6 mg, 4.967 mmol) was added to a stirred solution of magnesium turnings (119.2 mg, 4.967 mmol) and iodine (10 mg) in THF (2.0 mL) at rt. The resulting reaction mixture was stirred for 30 min at rt followed by the addition of (3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-1H- imidazol-2-yl)methanone (100 mg, 0.331 mmol) at 0 °C . The resulting reaction mixture was warmed to rt for 2 h. The reaction mixture was diluted with NH4Cl solution (5 mL) and extracted with ethyl acetate (10 mL × 2). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography (SiO2, 0-50% EtOAc / PE) to afford (3-chloro-4-fluoro- phenyl) (4-(methylsulfonyl)-1H-imidazol-2-yl) (6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methanol (0.1 g, 54%). Step 3: To a stirred solution of (3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-1H-imidazol-2-yl)(6-(2,2,2-trifluo- roethoxy)pyridin-3-yl)methanol (440 mg, 0.917 mmol), acetic acid (5.0 mL, 0.125 mmol) and fuming hydrochloric acid in water (2.0 mL, 0.025 mmol) at rt was added stannous chloride dihydrate (1241.5 mg, 5.502 mmol). The resulting reaction mixture was heated to 120 °C for 18 h. The reaction mixture was concentrated under reduced pressure, diluted with water (5 mL) and extracted with ethyl acetate (10 mL × 2). The combined organic layers were dried over sodium sulphate, filtered and concentrated under reduced pressure to get the crude product, which was purified by Prep HPLC followed by SFC to the title compound (0.03 g, 7%). LCMS m / z = 464 [M+H]+;1H- NMR (400 MHz, DMSO-d6): 12.90 (s, 1H), 8.14 (d, 1H), 7.82 (s, 1H), 7.76 (dd, 1H), 7.52 (dd, 1H), 7.40 (t, 1H), 7.32-7.28 (m, 1H), 6.99 (d, 1H), 5.71 (s, 1H), 5.00-4.93 (m, 2H), 3.10 (s, 3H). 80 GRA 4216-foreign filing Example 89 2-((3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-1H-imidazol-2-yl)methyl)-4-fluoroaniline Step 1: Sodium borohydride (0.119 g, 3.234 mmol) was added to a stirred solution of (3-chloro-4-fluorophenyl) (4-(methylsulfonyl)-1-((2-(trimethylsilyl) ethoxy) methyl)-1H-imidazol-2-yl) methanone (intermediate 25, mix- ture of regioisomers, 0.700 g, 1.617 mmol) in methanol (10 mL) at 0 °C, and the resulting mixture was stirred at 0 °C for 1 h. The reaction mixture was concentrated under reduced pressure. The obtained crude material was purified by flash chromatography (SiO2, 0-70% EtOAc / PE) to afford (3-chloro-4-fluorophenyl) (4-(methyl- sulfonyl)-1-((2-(trimethylsilyl) ethoxy) methyl)-1H-imidazol-2-yl) methanol and the corresponding SEM regioi- somer (0.450 g, 64%). Step 2: (3-Chloro-4-fluorophenyl) (4-(methylsulfonyl)-1-((2-(trimethylsilyl) ethoxy) methyl)-1H-imidazol-2-yl) methanol (mixture of regioisomers, 0.500 g, 1.14 mmol) was dissolved in 4 M HCl in 1,4-dioxane (5 mL) and the mixture was stirred at rt for 18 h. The reaction mixture was concentrated under reduced pressure. The obtained crude product was purified by Prep-HPLC to afford (3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-1H-imidazol- 2-yl)methanol (0.320 g, 91%). Step 3: p-Toluenesulfonic acid monohydrate (0.280 g, 1.477 mmol) was added to a stirred solution of (3-chloro- 4-fluorophenyl)(4-(methylsulfonyl)-1H-imidazol-2-yl)methanol (0.150 g, 0.492 mmol) and 4-fluoroaniline (0.164 g, 1.477 mmol) in toluene (10 mL) at rt and the mixture was then heated to 120 °C for 4 h. The reaction mixture was concentrated under reduced pressure. The obtained crude product was purified by Prep-HPLC to yield the title compound (0.030 g, 15%). LCMS m / z = 398 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.80 (s, 1H), 7.80 (s, 1H), 7.41 - 7.35 (m, 2H), 7.25 - 7.21 (m, 1H), 6.88 - 6.84 (m, 1H), 6.69 - 6.66 (m, 1H), 6.55 (dd, 1H), 5.69 (s, 1H), 4.92 (s, 2H), 3.09 (s, 3H). Example 91 2- -4-((methylsulfonyl)methyl)-1H-imidazole 81 GRA 4216-foreign filing Step 1: To a stirred solution of methyl 2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole-4-carboxylate (in- termediate 9, 1.8 g, 4.545 mmol) in DMF (20.0 mL) was added NaH (60% in mineral oil, 0.275 g, 6.818 mmol) at 0 °C and the reaction mixture was stirred at 0 °C for 15 min. Then, SEM-Cl (1.6 mL, 9.09 mmol) was added to the reaction mixture at 0 °C and the reaction mixture was stirred at rt for 16 h. The reaction mixture was cooled to 0 °C and quenched with NH4Cl solution. The aqueous layer was extracted with ethyl acetate (2 × 100 mL). The combined organic layers were washed with brine, dried over Na2SO4and concentrated under reduced pressure to get the crude product, which was purified by column chromatography (SiO2, 0-60% EtOAc / Hex) to yield methyl 2-[bis(3-chloro-4-fluorophenyl)methyl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole-4-carboxylate and methyl 2-[bis(3-chloro-4-fluorophenyl)methyl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole-5-carbox- ylate (1.0 g, 75%); LCMS m / z = 523 [M+H]+. Step 2: To a stirred solution of methyl 2-(bis(3-chloro-4-fluorophenyl)methyl)-1-((2-(trimethylsilyl)ethoxy)me- thyl)-1H-imidazole-5-carboxylate and methyl 2-[bis(3-chloro-4-fluorophenyl)methyl]-1-{[2-(trimethylsilyl)eth- oxy]methyl}-1H-imidazole-5-carboxylate (1.1 g, 2.09 mmol) in THF (30.0 mL) was added NaBH4(1.0 g, 27.186 mmol) at rt and the reaction mixture was then heated to 60 °C followed by the addition of MeOH (7.0 mL) dropwise at 60 °C. The reaction mixture was then heated to 60 °C for 16 h. The reaction mixture was cooled to 0 °C, diluted with water and extracted with ethyl acetate (3 × 100 mL). The combined organic layers were dried over anhydrous Na2SO4and concentrated under reduced pressure to get the crude product which was purified by CombiFlash column chromatography (SiO2, 0-70% EtOAc / Hex) to yield (2-(bis(3-chloro-4-fluorophenyl)me- thyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)methanol and the corresponding SEM regioisomer (0.7 g, 67%); LCMS m / z = 499 [M+H]+. Step 3: To a stirred solution of (2-(bis(3-chloro-4-fluorophenyl)methyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H- imidazol-5-yl)methanol (mixture of regioisomers, 0.4 g, 0.802 mmol) in DCM (15.0 mL) was added thionyl chlo- ride (0.29 mL, 4.00 mmol) at 0 °C and the mixture was then stirred at rt for 2 h. The reaction mixture was concen- trated and then diluted with ethyl acetate (40 mL). The organic layer was washed with sodium bicarbonate solution (15 mL), dried over Na2SO4 and evaporated under reduced pressure. The resulted crude compound was dissolved in THF (15 mL) followed by the addition of TEA (0.34 mL, 2.405 mmol) and NaSMe (0.28 g, 4.0 mmol) at 0 °C. The mixture was then stirred at rt for 16 h. The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (3 × 30 mL). The combined organic layers were washed with brine (20 mL), dried over Na2SO4 and evaporated under reduced pressure. The residue was purified by CombiFlash chromatography (SiO2, 0-30% EtOAc / Hex) to afford 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-((methylthio)methyl)-1-((2-(trimethylsilyl)eth- oxy)methyl)-1H-imidazole and the corresponding SEM regioisomer (0.26 g, 61%); LCMS m / z = 529 [M+H]+. Step 4: To a stirred solution 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-((methylthio)methyl)-1-((2-(trimethylsi- lyl)ethoxy)methyl)-1H-imidazole (mixture of regioisomers, 0.25 g, 0.473 mmol) in DCM (10.0 mL) was added m-CPBA (70 %, 0.232 g, 0.947 mmol) at 0 °C and the reaction mixture was stirred at rt for 3 h. To the reaction mixture was then added NaHCO3solution (10 mL) and the mixture was stirred for 30 minutes. The mixture was extracted with ethyl acetate (3 x 30 mL), the combined organic layers were dried over Na2SO4and evaporated under reduced pressure. The crude material was purified by CombiFlash column chromatography (SiO2, 0-70% EtOAc / PE) to yield 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-((methylsulfonyl)methyl)-1-((2-(trimethylsilyl)eth- oxy)methyl)-1H-imidazole and the corresponding SEM regioisomer (0.2 g, 42%). LCMS m / z = 561 [M+H]+. Step 5: To a stirred solution of 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-((methylsulfonyl)methyl)-1-((2-(trime- thylsilyl)ethoxy)methyl)-1H-imidazole (mixture of regioisomers, 0.13 g, 0.232 mmol) in ethanol (2 mL) was 82 GRA 4216-foreign filing added HCl (4M in dioxane, 2 mL) at rt and the reaction mixture was then heated to 70 °C for 5 h. The solvent was then evaporated under reduced pressure and the residue was purified by prep-HPLC to obtain the title compound (0.055 g, 55%). LCMS m / z = 431 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.1 (brs, 1H), 7.54-7.52 (m, 2H), 7.39-7.29 (m, 4H), 7.14 (s, 1H), 5.63 (s, 1H), 4.31 (s, 2H), 2.93 (s, 3H). Example 92 2-((3-chloro-4-fluorophenyl)(4-(trifluoromethyl)cyclohexyl)methyl)-4-(methylsulfonyl)-1H-imidazole Step 1: HATU (11.630 g, 30.586 mmol) was added portionwise to a stirred solution of 4-(trifluoromethyl) cyclo- hexane-1-carboxylic acid (5.0 g, 25.488 mmol), N, O-dimethyl hydroxylamine hydrochloride (2.983 g, 30.586 mmol) and N, N-Diisopropylethylamine (17.430 mL, 101.953 mmol) in DMF (50 mL) at 0 °C under an argon atmosphere. The mixture was allowed to warm to rt and was stirred for 4 h. The reaction mixture was then cooled to 0 °C, quenched with a saturated aqueous solution of NaHCO3(30 mL) and extracted with EtOAc (2 x 100 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and the solvent was evaporated under reduced pressure. The crude product was purified by 100-200 silica gel column chromatography (SiO2, 25% EtOAc / PE) to afford N-methoxy-N-methyl-4-(trifluoromethyl) cyclohexane-1-carboxamide (5.6 g, 91%). Step 2: LDA (2M in THF, 13.061 mL, 26.123 mmol) was added dropwise to a stirred solution of 4-iodo-1-((2- (trimethylsilyl)ethoxy)methyl)-1H-imidazole (intermediate 22, mixture of regioisomers, 7.7 g, 23.748 mmol) in THF (30 mL) at ^78 °C under an argon atmosphere. The resulting reaction mixture was stirred at this temperature for 1 h followed by the addition of a solution of (1s,4s)-N-methoxy-N-methyl-4-(trifluoromethyl)cyclohexane-1- carboxamide (5.681 g, 23.748 mmol) in THF (40 mL). The resulting reaction mixture was stirred for 1 h at ^78 °C. The reaction mixture was quenched with saturated NH4Cl solution (300mL), diluted with water (150 mL) and extracted with EtOAc (2 x 250 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography (SiO2, 0-20% EtOAc / PE) to afford (5-iodo-1-((2-(trimethylsilyl) ethoxy) methyl)-1H-imidazol- 2-yl) ((trans)-4-(trifluoromethyl) cyclohexyl) methanone and the corresponding SEM regioisomer (6 g, 50%). Step 3: 4-Bromo-2-chloro-1-fluorobenzene (2.084 g, 9.952 mmol) was added in one portion to a stirred solution of magnesium turnings (238.857 mg, 9.952 mmol) and Iodine (2 mg) in THF (7 mL) at rt under an argon atmos- phere. The temperature of the reaction was raised to 60 °C. The reaction mixture was allowed to come to rt and was stirred for 1 h. The reaction mixture was cooled to 0 °C and a solution of (4-iodo-1-((2-(trimethylsilyl) ethoxy) methyl)-1H-imidazol-2-yl) ((trans)-4-(trifluoromethyl) cyclohexyl) methanone (mixture of regioisomers, 1.0 g, 1.990 mmol) in THF (33 mL) was added dropwise. The reaction mixture was warmed to rt and was stirred for 1 h. 83 GRA 4216-foreign filing The reaction mixture was quenched with NH4Cl solution (150 mL) and extracted with ethyl acetate (3×150 mL). The combined organic layers were washed with brine (50 mL), dried over Na2SO4,filtered and then concentrated under reduced pressure. The crude product was purified by column chromatography (SiO2, 35% EtOAc / PE) af- ford (3-chloro-4-fluorophenyl) (4-iodo-1-((2-(trimethylsilyl) ethoxy) methyl)-1H-imidazol-2-yl) ((trans)-4-(tri- fluoromethyl) cyclohexyl) methanol and the corresponding SEM regioisomer (0.7 g, 55%). Step 4: To a stirred solution of (3-chloro-4-fluorophenyl) (4-iodo-1-((2-(trimethylsilyl) ethoxy) methyl)-1H-imid- azol-2-yl) ((trans)-4-(trifluoromethyl) cyclohexyl) methanol (mixture of regioisomers, 0.7 g, 1.106 mmol) and methylsulfinic acid sodium salt (451.229 mg, 4.424 mmol) dissolved in DMSO (20 mL) was added sodium hy- droxide powder (44.238 mg, 1.106 mmol). The mixture was degassed with argon gas, followed by the addition of copper(I) iodide (126.377 mg, 0.664 mmol) and L-Proline (127.328 mg, 1.106 mmol). The resulting reaction mix- ture was heated to 150 °C for 2 h under microwave irradiation. The reaction mixture was cooled to rt, filtered through a celite bed, the celite bed was washed with 10% methanol in dichloromethane (300 mL) and the filtrate was washed with water (2×100 mL). The organic layer was dried over Na2SO4and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO2, 35% EtOAc / PE) to afford (3-chloro- 4-fluorophenyl) (4-(methyl sulfonyl)-1-((2-(trimethylsilyl) ethoxy) methyl)-1H-imidazol-2-yl) ((trans)-4-(trifluo- romethyl) cyclohexyl) methanol and the corresponding SEM regioisomer (348 mg, 53%). Step 5: To a solution of (3-chloro-4-fluorophenyl) (4-(methyl sulfonyl)-1-((2-(trimethylsilyl) ethoxy) methyl)-1H- imidazol-2-yl) ((trans)-4-(trifluoromethyl) cyclohexyl) methanol (mixture of regioisomers, 320 mg, 0.547 mmol) in acetic acid (5 mL) was added stannous chloride anhydrous (740.434 mg, 3.281 mmol) followed by conc. hy- drochloric acid (1.6 mL) at rt. The resulting reaction mixture was heated to 120 °C for 2 h. The reaction mixture was cooled to rt, diluted with water (10 mL), basified with NaHCO3solution (pH=8) and extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with brine (10 mL), dried over Na2SO4and concen- trated under reduced pressure to afford (3-chloro-4-fluorophenyl) (4-(methyl sulfonyl)-1H-imidazol-2-yl) ((trans)- 4-(trifluoromethyl) cyclohexyl) methanol (430 mg, crude). Step 6: To a solution of (3-chloro-4-fluorophenyl) (4-(methyl sulfonyl)-1H-imidazol-2-yl) ((trans)-4-(trifluorome- thyl) cyclohexyl) methanol (290 mg, 0.638 mmol) in acetic acid (25 mL) was added stannous chloride dehydrate (863.181 mg, 3.825 mmol) followed by fuming hydrochloric acid (37% solution in water, 20 mL) at rt. The result- ing reaction mixture was heated to 120 °C for 16 h. The reaction mixture was cooled to rt and was concentrated under reduced pressure. The residue was diluted with water (10 mL), basified with NaHCO3solution (pH=8) and then extracted with ethyl acetate (3x25 mL). The combined organic layers were washed with brine (15 mL), dried over Na2SO4, filtered and then concentrated under reduced pressure. Similarly, using above experimental protocol another 0.127 mg of (3-chloro-4-fluorophenyl) (4-(methyl sulfonyl)- 1H-imidazol-2-yl) ((trans)-4-(trifluoromethyl) cyclohexyl) methanol was used. The combined crudes were puri- fied by prep HPLC to afford Peak 1 of the title compound (66 mg) and Peak 2 of the title compound (90 mg). Peak 1, example 92a: LCMS m / z = 439 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.76 (s, 1H), 7.78 (s, 1H), 7.60 (d, 1H), 7.37 (d, 2H), 3.79 (d, 1H), 3.08 (s, 3H), 2.19-2.07 (m, 2H), 1.85-1.78 (m, 2H), 1.55-1.52 (m, 1H), 1.42-1.39 (m, 1H), 1.27-1.13 (m, 2H), 1.07-0.96 (m, 2H). Chiral SFC: column: Chiralpak AD-H (4.6 x 250 mm) 84 GRA 4216-foreign filing 5 m; co-solvent: 0.5% DEA in MeOH, flow: 3 mL / min; % of co-solvent: 15%; ABPR: 1500 psi T: 30 °C; Rt = 1.00 min (first eluting). Peak 2, example 92b: LCMS m / z = 439 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.76 (s, 1H), 7.78 (s, 1H), 7.60 (d, 1H), 7.37 (d, 2H), 3.79 (d, 1H), 3.08 (s, 3H), 2.19-2.07 (m, 2H), 1.85-1.78 (m, 2H), 1.55-1.52 (m, 1H), 1.42-1.39 (m, 1H), 1.27-1.13 (m, 2H), 1.07-0.96 (m, 2H). Chiral SFC: column: Chiralpak AD-H (4.6 x 250 mm) 5 m; co-solvent: 0.5% DEA in MeOH, flow: 3 mL / min; % of co-solvent: 15%; ABPR: 1500 psi T: 30 °C; Rt = 2.01 min (second eluting). Example 93 3-chloro-6-((4-chlorophenyl)(4-(methylsulfonyl)-1H-imidazol-2-yl)methyl)-2-(trifluoromethyl)pyridine Step 1: To a solution of 3,6-dichloro-2-(difluoromethyl)pyridine (2.5 g, 11.628 mmol) in ethanol (50 mL) was added TEA (2 mL, 13.953mmol) and the mixture was degassed with argon for 10 minutes. Then potassium vinyl-trifluoroborate was added (1.9 g, 13.953 mmol) followed by the addition of PdCl2(dppf) DCM (0.43 g, 0.581mmol) at rt. The mixture was then heated to 110 °C for 3 h in a sealed tube. The reaction mixture was cooled to rt and filtered through a celite bed, the filtrate was evaporated at low temperature (~40°C) under reduced pressure.The resulting crude was purified by CombiFlash column chromatography (SiO2, hexane) to obtain 3-chloro-6-ethenyl-2-(trifluoromethyl)pyridine (1.8 g, 75%). Step 2: To a solution of 3-chloro-6-ethenyl-2-(trifluoromethyl) pyridine (1.8 g, 8.696 mmol) in dioxane-water (3:1, 60 mL) was added NMO (2.6 mL, 9.565 mmol, 50% in water) followed by OsO4(1.2 mL, 0.174 mmol, 0.15 M in dioxane) at rt. The mixture was then stirred at the same temperature for 3 h. Then NaIO4 (19 g, 86.957 mmol) was added and stirring was continued at rt for 1 h. The reaction mixture was quenched with saturated sodium bi- carbonate solution and extracted with EtOAc (3 x 100 mL). The combined organic layers were washed with brine solution, dried over anhydrous Na2SO4and concentrated under reduced pressure to obtain 5-chloro-6-(trifluoro- methyl)picolinaldehyde which was used in the next step without further purification (1.5 g, 82%). Step 3: To a solution of 5-chloro-6-(trifluoromethyl) picolinaldehyde (0.1 g, 0.478 mmol) in THF (4 mL) was added (4-chlorophenyl) magnesium bromide (0.57 mL, 0.574 mmol, 1M in Et2O, 1.2 eq.) slowly at 0 °C. The mixture was then stirred at the same temperature for 1 h, before being quenched with saturated aqueous ammonium chloride solution. The mixture was extracted with EtOAc (2 x 20 mL), the combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The resulting crude product was purified by combi-flash column chromatography (SiO2, 30% EtOAc / Hex) to obtain [5-chloro-6-(trifluorome- thyl) pyridin-2-yl] (4-chlorophenyl) methanol (0.13 g, 84%). LCMS m / z = 322 [M+H]+. 85 GRA 4216-foreign filing Step 4: To a solution of [5-chloro-6-(trifluoromethyl) pyridin-2-yl] (4-chlorophenyl) methanol (0.13 g, 0.404 mmol) in THF (5 mL) was added MnO2(0.18 g, 2.019 mmol) at rt. The mixture was then stirred at the same temperature for 16 h. The reaction mixture was filtered through celite and the celite bed was washed with THF. The solvent was evaporated under reduced pressure. The residue was purified by combi-flash column chromatog- raphy (SiO2, 0-20% EtOAc / Hex) to obtain 3-chloro-6-[(4-chlorophenyl)carbonyl]-2-(trifluoromethyl)pyridine (0.1 g, 77%). Step 5: To a solution of DIPA (0.72 mL, 5.156 mmol) in THF (10 mL) was added n-BuLi (2.3 mL, 2 M in THF, 4.688 mmol) slowly at ^78°C under a nitrogen atmosphere. The mixture was stirred at the same temperature for 10 minutes, then allowed to warm to 0 °C for 30 minutes. The solution was again cooled to ^78°C and 4-iodo-1- ((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole (intermediate 22, mixture of regioisomers, 1.3 g, 3.906 mmol) in THF (10 mL) was added. The mixture was stirred at same temperature for 30 minutes, followed by the addition of a solution of 3-chloro-6-[(4-chlorophenyl)carbonyl]-2-(trifluoromethyl)pyridine (0.5 g, 1.563 mmol) in THF (10 mL) at the same temperature. The reaction mixture was slowly warmed to rt and was stirred for 6 h. The reaction mixture was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate (2 x 100 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The resulting crude product was purified by combi-flash column chromatography (SiO2, 0-10% EtOAc / Hex) to obtain (5-chloro-6-(trifluoromethyl)pyridin-2-yl)(4-chlorophenyl)(4-iodo-1-((2-(trime- thylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methanol and the corresponding SEM regioisomer (0.5 g, 50%). LCMS m / z = 645 [M+H]+. Step-6: To a solution of (5-chloro-6-(trifluoromethyl)pyridin-2-yl)(4-chlorophenyl)(4-iodo-1-((2-(trimethylsi- lyl)ethoxy)methyl)-1H-imidazol-2-yl)methanol (mixture of regioisomers, 0.5 g, 0.776 mmol) in 1,4-dioxane (20.0 mL) was added NaSMe (0.1 g, 1.32 mmol) and the mixture was degassed with argon for 10 min followed by the addition of Xantphos (0.07 g, 0.116 mmol) and Pd2(dba)3 (0.07 g, 0.078 mmol) at rt. The mixture was then heated to 110 °C for 16 h in a sealed tube. The mixture was then filtered through a celite bed and the celite bed was washed with EtOAc. The solvent was evaporated to get the crude material which was purified by CombiFlash column chromatography (SiO2, 10% EtOAc / Hex) to get (5-chloro-6-(trifluoromethyl)pyridin-2-yl)(4-chloro- phenyl)(4-(methylthio)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methanol and the corresponding SEM regioisomer (0.3 g, 68%). LCMS m / z = 564 [M+H]+. Step-7: To a solution of (5-chloro-6-(trifluoromethyl)pyridin-2-yl)(4-chlorophenyl)(4-(methylthio)-1-((2-(trime- thylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methanol (mixture of regioisomers, 0.32 g, 0.566 mmol) in acetic acid (5.0 mL) were added SnCl2(0.64 g, 3.398 mmol) and aqueous HCl (1 mL, 12 N). The mixture was heated to 120 °C for 24 h. The reaction mixture was cooled to rt and concentrated under reduced pressure to get the crude product which was basified with aqueous Na2CO3solution. The mixture was filtered through a celite bed and extracted with ethyl acetate (3 × 50 mL). The combined organic layers were washed with brine, dried over Na2SO4and concentrated under reduced pressure to get the crude material which was purified by combi-flash column chroma- tography (SiO2, 50% EtOAc / Hex) to get 3-chloro-6-[(4-chlorophenyl)[4-(methylsulfanyl)-1H-imidazol-2-yl]me- thyl]-2-(trifluoromethyl)pyridine (0.13 g, 55%). LCMS m / z = 418 [M+H]+. 86 GRA 4216-foreign filing Step-8: To a solution of 3-chloro-6-[(4-chlorophenyl)[4-(methylsulfanyl)-1H-imidazol-2-yl]methyl]-2-(trifluoro- methyl)pyridine (0.3 g, 0.718 mmol) in DCM (5.0 mL) was added m-CPBA (70%, 0.62 g, 2.153 mmol) at rt. The mixture was stirred at rt for 3 h and was then basified with saturated Na2SO3 solution, stirred for 30 minutes and extracted with ethyl acetate (3 × 50 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure to get the crude title compound which was purified by column chroma- tography (SiO2, EtOAc) (0.025 g, 8%). LCMS m / z = 450 [M+H]+.1H-NMR (400 MHz, DMSO-d6): 12.81 (bs, 1H), 8.25 (d, 1H), 7.84 (s, 1H), 7.74 (d, 1H), 7.44 (d, 2H), 7.36 (d, 2H), 5.91 (s, 1H), 3.08 (s, 3H). Example 130 2-((3-chloro-4-fluorophenyl)(5-chlorothiophen-2-yl)methyl)-4-methyl-5-(methylsulfonyl)-1H-imidazole Step 1: n-butyl lithium (2.5M, 4.474 mL, 11.186 mmol) was added dropwise to a solution of 2-bromo-5-chloro- thiophene (0.736 mL, 6.712 mmol) in THF (20.0 mL) at -78 °C under an argon atmosphere. The reaction was stirred at -78 °C for 15 min. After 15 min, (3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-1-((2-(trime- thylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methanone (regioisomeric mixture, 2.5 g, 5.593 mmol) in THF (10.0 mL) was added dropwise at the same temperature. The reaction was stirred at room temperature for 1 h. The reaction was quenched by the addition of sat. NH4Cl solution (50 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layers were dried over anhydrous Na2SO4 and the solvent was evaporated under reduced pressure to get the crude compound, which was purified by column chromatography (SiO2, 25-30% EtOAc / Hex) to afford (3-chloro-4-fluorophenyl)(5-chlorothiophen-2-yl)(5-methyl-4-(methylsulfonyl)-1-((2-(tri- methylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methanol (mixture of regioisomers, 0.9 g, 29%). Step 2: To a solution of (3-chloro-4-fluorophenyl)(5-chlorothiophen-2-yl)(5-methyl-4-(methylsulfonyl)-1-((2-(tri- methylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methanol (mixture of regioisomers, 0.9 g, 1.591 mmol) in acetic acid (9.0 mL) were added stannous chloride dihydrate (2.154 g, 9.548 mmol) and conc. HCl (1.8 mL) at room temperature. The resulting reaction mixture was heated to 100 °C for 16 h. The reaction mixture was concentrated under reduced pressure to get the crude product, which was basified with sat NaHCO3 solution (10 mL) and ex- tracted with EtOAc (3×20 mL). The combined organic layers were dried over sodium sulfate and evaporated under reduced pressure to afford the crude product which was purified by prep-HPLC to afford 100 mg of the racemic title compound. The racemic title compound was separetad into the individual stereoisomers using chiral SFC. LCMS m / z = 419 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.69 (brs, 1H), 7.59-7.57 (dd, 1H), 7.44-7.33 (m, 2H), 6.98 (d, 1H), 6.81 (d, 1H), 5.82 (s, 1H), 3.08 (s, 3H), 2.37 (s, 3H). Chiral SFC: column: Chiralpak IG (4.6 x 250 mm) 5 m; co-solvent: 0.5% diethylamine in MeOH, flow: 3 mL / min; % of co-solvent: 25%; ABPR: 1500 psi T: 30 °C; (130a) Rt = 1.25 min (first eluting), (130b) Rt = 1.70 min (second eluting). 87 GRA 4216-foreign filing Example 131 The title compound was prepared from the appropriate intermediates and reagents using an analogous method to that described for example 130. Example Name / Structure / Data 131 2-((3-chloro-4-fluorophenyl)(4-methyl-5-(methylsulfonyl)-1H-imidazol-2-yl)methyl)-5- (trifluoromethyl)thiazole LCMS m / z = 454 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.81 (brs, 1H), 8.42 (d, 1H), 7.71-7.69 (m, 1H), 7.46-7.44 (m, 2H), 6.21 (s, 1H), 3.10 (s, 3H), 2.39 (s, 3H). Example 132 2-((3-chloro-4-fluorophenyl)(3,3-difluorocyclopentyl)methyl)-4-methyl-5-(methylsulfonyl)-1H-imidazole Step 1: To a stirred solution of (3-chloro-4-fluorophenyl)(3,3-difluorocyclopentyl)(5-methyl-4-(methylsulfonyl)- 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methanol (intermediate 47, mixture of regioisomers, 0.8 g, 1.446 mmol) and stannous chloride dihydrate (1.958 g, 8.678 mmol) in acetic acid (8 mL) at room temperature was added conc. HCl (1.6 mL). The reaction mixture was heated to 100 °C for 18 h. The reaction mixture was concentrated under reduced pressure, the obtained residue was basified by using sat. NaHCO3 solution and ex- tracted with EtOAC (2 x 30 mL). The combined organic layers were washed with water (30 mL) and brine (30 mL) and then concentrated under reduced pressure to afford the crude compound, which was purified by prep HPLC (column: XSelect phenyl hexyl (19 x 250 mm) 5 m; 10 mM ammonium-bi-carbonate in water / MeCN as eluent) to yield two fractions with the desired compounds and later prep SFC to afford the title compounds. First eluting fractions from HPLC after SFC: 132a: LCMS m / z = 407 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.52 (s, 1H), 7.58-7.56 (dd, 1H), 7.40-7.33 (m, 2H), 3.95 (d, 1H), 3.06 (s, 1H), 2.99-2.88 (m, 1H), 2.35 (s, 3H), 2.33-2.00 (m, 2H), 1.89-1.72 (m, 3H), 1.45-1.38 (m, 1H).132b: LCMS m / z = 407 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.55 (s, 1H), 7.58-7.56 (dd, 1H), 7.40-7.34 (m, 2H), 3.95 (d, 1H), 3.06 (s, 1H), 2.99-2.88 (m, 1H), 2.35 (s, 3H), 2.33-2.00 (m, 2H), 1.89-1.72 (m, 3H), 1.45-1.38 (m, 1H). Chiral SFC: column: Chiralcel OX-H (4.6 x 250 mm) 5 m; co-solvent: iPrOH, flow: 3 mL / min; % of co-solvent: 15%; ABPR: 1500 psi T: 30 °C; (132a) Rt = 2.82 min (first eluting), (132b) Rt = 3.63 min (second eluting). 88 GRA 4216-foreign filing Second eluting fractions from HPLC after SFC: 132c: LCMS m / z = 407 [M+H]+;1H-NMR (400 MHz, DMSO- d6): 12.52 (s, 1H), 7.58-7.56 (dd, 1H), 7.40-7.33 (m, 2H), 3.95 (d, 1H), 3.06 (s, 1H), 2.99-2.88 (m, 1H), 2.35 (s, 3H), 2.33-2.00 (m, 2H), 1.89-1.72 (m, 3H), 1.45-1.38 (m, 1H).132d: LCMS m / z = 407 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.55 (s, 1H), 7.58-7.56 (dd, 1H), 7.40-7.34 (m, 2H), 3.95 (d, 1H), 3.06 (s, 1H), 2.99-2.88 (m, 1H), 2.35 (s, 3H), 2.33-2.00 (m, 2H), 1.89-1.72 (m, 3H), 1.45-1.38 (m, 1H). Chiral SFC: column: Chiralcel OX-H (4.6 x 250 mm) 5 m; co-solvent: iPrOH, flow: 3 mL / min; % of co-solvent: 15%; ABPR: 1500 psi T: 30 °C; (132c) Rt = 2.74 min (first eluting), (132d) Rt = 5.56 min (second eluting). Example 133 azetidin-3-yl(2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-4-yl)(imino)-l6-sulfanone Step 1: To a mixture of 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-iodo-1H-imidazole (intermediate 4, 0.5 g, 1.075 mmol), tert-butyl 3-mercaptoazetidine-1-carboxylate (0.305 g, 1.613 mmol) and cesium carbonate (1.051 g, 3.225 mmol) in 1,4-dioxane (20 mL) under a nitrogen atmosphere was added slowly Xantphos, (0.062 g, 0.108 mmol) followed by Pd2(dba)3(0.098 g, 0.108 mmol). The resulting reaction mixture was heated to 120 °C and stirred for 3 h in a sealed tube. The reaction mixture was filtered through a celite bed and the filterate was extracted with ethyl acetate (3×150 mL). The combined organic layers were were washed with brine (20 mL), dried over anhy- drous Na2SO4, filtered and concentrated under reduced pressure to get the crude product, which upon purification by reverse phase column chromatography 150 mg (26%) of tert-butyl 3-((2-(bis(3-chloro-4-fluorophenyl)methyl)- 1H-imidazol-4-yl)thio)azetidine-1-carboxylate. Step 2: To a solution of tert-butyl 3-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-4-yl)thio)azetidine-1- carboxylate (0.4 g, 0.760 mmol) in methanol (4.0 mL) at 0 °C was added ammonium carbonate (0.146 g, 1.52 mmol) followed by (diacetoxyiodo)benzene (0.441 g, 1.368 mmol). The resulting reaction mixture was stirred for 6 h at room temperature. The reaction mixture was concentrated under reduced pressure to obtain a residue, which was taken up in water (10 mL) and extracted with ethyl acetate (2×30 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to get the crude product, which after reveres phase column chromatography afforded 280 mg of tert-butyl 3-(2-(bis(3- chloro-4-fluorophenyl)methyl)-1H-imidazole-5-sulfonimidoyl)azetidine-1-carboxylate. Step 3: To a solution of tert-butyl 3-(2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole-5-sulfonimidoyl)azet- idine-1-carboxylate (0.19 g, 0.341 mmol) in DCM (1.9 mL) at 0 °C was added trifluoroacetic acid (0.95 mL). The resulting reaction mixture was stirred for 2 h at room temperature. The reaction mixture was quenched with sodium bicarbonate solution, diluted with ice water (20 mL) and adjusted the pH to 7.0 with sodium bicarbonate solution. 89 GRA 4216-foreign filing The mixture was then extracted with 10% MeOH in DCM (2×50 mL). The combined organic layers were washed with brine (2 x 10 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to get the crude product, which upon reverse phase column chromatography followed by prep HPLC gave 45 mg of the racemic title compound. The racemic compound was separetad in the individual enantiomers using chiral SFC. LCMS m / z = 457 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.56 (brs, 1H), 7.67 (s, 1H), 7.55-7.52 (m, 2H), 7.41-7.36 (m, 2H), 7.34-7.30 (m, 2H), 5.68 (s, 1H), 4.23-4.16 (m, 1H), 4.05-3.96 (brs, 2H), 3.80-3.74 (m, 2H), 3.52-3.45 (m, 2H). Chiral SFC: column: Chiralcel OX-H (4.6 x 250 mm) 5 m; co-solvent: 0.5% iPrNH2in iPrOH, flow: 3 mL / min; % of co-solvent: 35%; ABPR: 1500 psi T: 30 °C; (133a) Rt = 7.18 min (first eluting), (133b) Rt = 9.00 min (second eluting). Example 135 2-((4-chloro-3-fluorophenyl)(chroman-3-yl)methyl)-4-methyl-5-(methylsulfonyl)-1H-imidazole Step 1: A solution of ((3-chloro-4-fluorophenyl)(chroman-3-yl)(5-methyl-4-(methylsulfonyl)-1-((2-(trimethyl- silyl)ethoxy)methyl)-1H-imidazol-2-yl)methanol (intermediate 48, mixture of intermediates, 300 mg, 0.516 mmol) in 1,4-dioxane (5 mL) was added to 4 M HCl in 1,4-dioxane (5 mL). The resulting reaction mixture was stirred for 6 h at room temperature. Excess voltiles were removed under reduced pressure and azeotroped with toluene (2×5 mL) to afford (4-chloro-3-fluorophenyl)(chroman-3-yl)(5-methyl-4-(methylsulfonyl)-1H-imidazol- 2-yl)methanol (300 mg, crude). Step 2: To a solution of (4-chloro-3-fluorophenyl)(chroman-3-yl)(5-methyl-4-(methylsulfonyl)-1H-imidazol-2- yl)methanol (250 mg, 0.554 mmol) in acetic acid (5 mL) was added tin(II) chloride (630.726 mg, 3.327 mmol). The resulting reaction mixture was stirred at 100 °C for 6 h. Excess voltiles were removed under reduced pressure, the residue was quenched with saturated NaHCO3 solution (10 mL), diluted with water (10 mL) and extracted with ethyl acatate (3x20 mL). The combined organic layers were washed with brine (20 mL) and water (20 ml), dried over anhydrous sodium sulphate, filtered and the filtrate was concentrated under reduced pressure to get the crude product, which was purified by chiral prep-HPLC (column: XBridge C8 (19 x 250 mm) 5 m; 0.1% formnic acid in water / (MeCN / MeOH 1:1) as eluent) to afford the title compounds as two fractions of two stereoisomers each. First eluting fraction: 9 mg, 2%, over 3 steps; second eluting fraction: 7 mg, 5%. First eluting fraction from chiral HPLC: 135a: LCMS m / z = 435 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 11.97 (bs, 1H) ,7.59 (t, 1H), 7.43 (dd, 1H), 7.24 (dd, 1H), 7.09^7.01 (m, 2H), 6.83^6.75 (m, 2H), 3.97 (d, 1H), 3.88 (d, 1H), 3.71^3.67 (m, 1H), 3.08 (s, 3H), 2.90^2.80 (m, 2H), 2.48-2.46 (m, 1H), 2.35 (s, 3H). Chiral SFC: column: 90 GRA 4216-foreign filing Chiralpak IK (4.6 x 150 mm) 5 m; co-solvent: iPrOH, flow: 3 mL / min; % of co-solvent: 15%; ABPR: 1500 psi T: 30 °C; (135a) Rt = 4.64 min (first eluting). Second eluting fraction from chiral HPLC: 135b: LCMS m / z = 435 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 10.95 (bs, 1H) ,7.57 (t, 1H), 7.38 (dd, 1H), 7.17 (dd, 1H), 7.09^7.04 (m, 1H), 6.96 (d, 1H), 6.81^ 6.74 (m, 2H), 4.11 (d, 1H), 3.95 (d, 1H), 3.79 ^3.84 (m, 1H), 3.09 (s, 3H), 2.94^2.85 (m, 1H), 2.52^2.41 (m, 2H), 2.36 (s, 3H); Chiral SFC: column: Chiralpak IK (4.6 x 150 mm) 5 m; co-solvent: iPrOH, flow: 3 mL / min; % of co-solvent: 15%; ABPR: 1500 psi T: 30 °C; (135b) Rt = 6.22 min (second eluting). Example 141 (2-(bis(3-chloro-4,5-difluorophenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6-sulfanone Step 1: To a stirred solution of 2-(bis(3-chloro-4,5-difluorophenyl)methyl)-5-methyl-4-(methylthio)-1-((2-(trime- thylsilyl)ethoxy)methyl)-1H-imidazole (intermediate 31, mixture of regioisomers, 0.5 g, 0.883 mmol) in MeOH (10 mL) were added (NH4)2CO3(0.254 g, 2.648 mmol) and diacetoxyiodobenzene (0.853 g, 2.648 mmol). The reaction mixture was stirred at room temperature for 16 h. Thee reaction mixture was concentrated under reduced pressure to get the crude product, which was purified by column chromatography (SiO2, 0-40% EtOAc / Hex) to afford {2-[bis(3-chloro-4,5-difluorophenyl)methyl]-5-methyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imid-azol-4-yl}(imino)methyl- -sulfanone and the corresponding SEM regioisomer (0.32 g, 60%). LCMS m / z = 596[M+H]+. Step 2: To a stirred solution of {2-[bis(3-chloro-4,5-difluorophenyl)methyl]-5-methyl-1-{[2-(trimethylsilyl)eth-oxy]methyl}-1H-imidazol-4-yl}(imino)methyl- -sulfanone (mixture of regioisomers, 0.29 g, 0.485 mmol) inDCM (7.0 mL) was added TFA (0.744 mL, 9.706 mmol) at 0 °C and the mixture was then stirred at rom temper- ature for 2 h. The reaction mixture was poured into ice cold NaHCO3 solution and extracted with DCM (2 × 50 mL). The combined organic layers were washed with water (20 mL) and brine (20 mL), dried over anhydrous Na2SO4solution, filtered and concentrated under reduced pressure to get the crude product, which was purified by prep-HPLC to afford 2-[bis(3-chloro-4,5-difluorophenyl)methyl]-4-[imino(methane)sulfinyl]-5-methyl-1H-imid- azole (0.075 g, 33%). LCMS m / z = 466 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.38 (s, 1H), 7.45-7.50 (m, 4H), 5.63 (s, 1H), 3.93 (s, 1H), 2.99 (s, 3H), 2.37 (s, 3H). Chiral HPLC: column: Chiralpak IC (4.6 x 250 mm) 5 m, mobile phase: Hexane / EtOH / iPrNH280 / 20 / 0.1, flow rate: 1.0 mL / min; 141a: Rt = 7.56 min (first eluting), 141b: Rt = 9.30 min (second eluting). 91 GRA 4216-foreign filing Example 142-145, 185. The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for example 141. Example Name / Structure / Data 142a, 142b (2-(bis(5-chloro-2,4-difluorophenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)- l6-sulfanone LCMS m / z = 466 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.49 (s, 1H), 7.60 (t, 2H), 7.45- 7.40 (m, 2H), 5.90 (s, 1H), 3.94 (s, 1H), 2.96 (s, 3H), 2.38 (s, 3H). Chiral SFC: column: Chiralpak IC (4.6 x 250 mm) 5 m; co-solvent: 0.3% iPrNH2 in iPrOH, flow: 3 mL / min; % of co-solvent: 40%; ABPR: 100 bar; T: 35 °C; (142a) Rt = 2.08 min (first eluting), (142b) Rt = 2.99 min (second eluting). 143a, 143b (2-(bis(4-chloro-2-fluorophenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6- sulfanone LCMS m / z = 430 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.48 (s, 1H), 7.46 (d, 2H), 7.30 (d, 2H), 7.18 (q, 2H), 5.89 (s, 1H), 3.87 (s, 1H), 2.95 (s, 3H), 2.37 (s, 3H). Chiral HPLC: column: Chiralpak IC (4.6 x 250 mm) 5 m, mobile phase: Hexane / EtOH / iPrNH270 / 30 / 0.1, flow rate: 1.0 mL / min; 143a: Rt = 6.62 min (first eluting), 143b: Rt = 8.45 min (second elu- ting). 145a, 145b (2-(bis(4-(trifluoromethoxy)phenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6- sulfanone 92 GRA 4216-foreign filing LCMS m / z = 494 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.40 (s, 1H), 7.43 (d, 4H), 7.35 (d, 4H), 5.65 (s, 1H), 3.86 (s, 1H), 2.98 (s, 3H), 2.37 (s, 3H). Chiral SFC: column: Chiralpak IC (4.6 x 250 mm) 5 m; co-solvent: 0.3% iPrNH2 in iPrOH, flow: 3 mL / min; % of co-solvent: 30%; ABPR: 100 bar; T: 35 °C; (145a) Rt = 1.65 min (first eluting), (145b) Rt = 2.03 min (second eluting). 185a, 185b (2-(bis(3-(difluoromethyl)-4-fluorophenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(me- thyl)-l6-sulfanone LCMS m / z = 462 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.1 (s, 1H), 7.60-7.51 (m, 4H), 7.38-7.05 (m, 4H), 5.74 (s, 1H), 3.87 (s, 1H), 2.97 (s, 3H), 2.31 (s, 3H). Chiral SFC: column: Chiralpak IC (4.6 x 250 mm) 5 m; co-solvent: 0.3% iPrNH2in iPrOH, flow: 3 mL / min; % of co-solvent: 40%; ABPR: 100 bar; T: 35 °C; (185a) Rt = 1.64 min (first eluting), (185b) Rt = 2.04 min (second eluting). Example 147 (2- imidazol-4-yl)(imino)(methyl)-l6-sulfanone F Step 1: To a stirred solution of 2-(bis(3-fluoro-4-(trifluoromethoxy)phenyl)methyl)-5-methyl-4-(methylthio)-1- ((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole (intermediate 34, mixture of regioisomers, 1 g, 1.59 mmol) in 93 GRA 4216-foreign filing MeOH (18 mL) were added diacetoxyiodobenzene (1.5 g, 4.77 mmol) and ammonium carbonate (0.5 g, 4.77 mmol) at room temperature. The resulting solution was stirred at room temperature for 3 h. The reaction mixture was diluted with ethyl acetate (60 mL), washed with water (30 mL) and brine (20 mL). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure to afford the crude product, which was purified by column chromatography (SiO2, 40% EtOAc / Hex) to afford (2-(bis(3-fluoro-4-(trifluoromethoxy)phe- nyl)methyl)-5-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)(imino)(methyl)-l6-sulfanone and the corresponding SEM regioisomer. Yield: 57% (0.6 g). LCMS m / z = 660 [M+H]+. Step 2: To a stirred solution of (2-(bis(3-fluoro-4-(trifluoromethoxy)phenyl)methyl)-5-methyl-1-((2-(trimethylsi- lyl)ethoxy)methyl)-1H-imidazol-4-yl)(imino)(methyl)-l6-sulfanone (mixture of regioisomers, 500 mg, 0.76 mmol) in DCM (5 mL) was added 4 M HCl in dioxane (10 mL) at 0 °C. The resulting solution was stirred at room temperature for 5 h. The reaction mixture was concentrated, the obtained residue was diluted with water (20 mL), basified using aqueous NaHCO3 solution and extracted with ethylacetate (2 × 30 mL). The combined organic layers were washed with brine (20 mL), dried over Na2SO4and concentrated under reduced pressure to afford the crude compound, which was purified by reverse phase prep-HPLC to afford the title compound. Yield: 51% (210 mg). LCMS m / z = 530 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.43 (bs, 1H), 7.58-7.54 (m, 2H), 7.51-7.48 (m, 2H), 7.30-7.28 (m, 2H), 5.71 (s, 1H), 3.89 (m, 1H), 2.99 (s, 3H), 2.37 (s, 3H). Chiral SFC: column: Chiralpak IC (4.6 x 250 mm) 5 m; co-solvent: 0.3% iPrNH2in iPrOH, flow: 3 mL / min; % of co-solvent: 40%; ABPR: 100 bar; T: 35 °C; (147a) Rt = 2.44 min (first eluting), (147b) Rt = 3.39 min (second eluting). Example 140, 144, 186. The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for example 147. Example Name / Structure / Data 140a, 140b (2-(bis(3-chloro-2,4-difluorophenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)- l6-sulfanone LCMS m / z = 466 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.49 (bs, 1H), 7.36-7.22 (m, 4H), 5.98 (s, 1H), 3.90 (s, 1H), 2.96 (s, 3H), 2.38 (s, 3H). Chiral SFC: column: Chiralpak IC (4.6 x 250 mm) 5 m; co-solvent: 0.3% iPrNH2in iPrOH, flow: 3 mL / min; % of co-solvent: 40%; ABPR: 100 bar; T: 35 °C; (140a) Rt = 2.13 min (first eluting), (140b) Rt = 3.08 min (second eluting). 94 GRA 4216-foreign filing 144a, 144b (2-(bis(2-chloro-4-fluorophenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6- sulfanone LCMS m / z = 430 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.54 (bs, 1H), 7.52-7.49 (m, 2H), 7.24-7.20 (m, 2H), 7.01-6.95 (m, 2H), 6.03 (s, 1H), 3.87 (m, 1H), 2.94 (s, 3H), 2.37 (s, 3H). Chiral SFC: column: Chiralpak IC (4.6 x 250 mm) 5 m; co-solvent: 0.3% iPrNH2in iPrOH, flow: 3 mL / min; % of co-solvent: 40%; ABPR: 100 bar; T: 35 °C; (144a) Rt = 2.53 min (first eluting), (144b) Rt = 3.79 min (second eluting). 186a, 186b (2-(bis(4-chloro-2-methoxyphenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6- sulfanone LCMS m / z = 454 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.23 (bs, 1H), 7.06 (s, 2H), 6.95-6.94 (m, 2H), 6.87-6.84 (m, 2H), 5.93 (s, 1H), 3.78 (m, 1H), 3.73 (s, 6H), 2.92 (s, 3H), 2.34 (s, 3H). Chiral SFC: column: Chiralpak IC (4.6 x 250 mm) 5 m; co-solvent: 0.3% iPrNH2in iPrOH, flow: 3 mL / min; % of co-solvent: 40%; ABPR: 100 bar; T: 35 °C; (186a) Rt = 2.25 min (first eluting), (186b) Rt = 2.66 min (second eluting). Example 181 4- 4-fluorophenyl)methyl]-1H-imidazole 95 GRA 4216-foreign filing Step 1: To a stirred solution of 2-(bis(3-chloro-4-fluorophenyl) methyl)-4-iodo-1H-imidazole (intermediate 4, 0.4 g, 0.86 mmol) in 1,4-dioxane (12 mL) was added tert-butyl 3-mercaptoazetidine-1-carboxylatetert-butyl 3-mer- captoazetidine-1-carboxylate (0.196 g, 1.032 mmol) and the mixture was degassed with argon gas for 10 min. Pd2(dba)3(0.08 g, 0.086 mmol), Xantphos (0.1 g, 0.172 mmol) and DIPEA (0.45 mL, 2.58 mmol) were added and the reaction mixture was heated for 16 h at 100 °C in a sealed tube. The reaction mixture was diluted with water (15 mL) and extracted with ethyl acetate (3 × 50 mL). The combined organic layers were washed with brine and dried over Na2SO4. The solvent was evaporated under reduced pressure. The crude material was purified by col- umn chromatography (SiO2, 0-40% EtOAc / Hex) to obtain tert-butyl 3-({2-[bis(3-chloro-4-fluorophenyl) methyl]- 1H-imidazol-4-yl}sulfanyl)azetidine-1-carboxylate (0.24 g, 53%). LCMS m / z = 526 [M+H]+. Step 2: To a solution of tert-butyl 3-({2-[bis(3-chloro-4-fluorophenyl) methyl]-1H-imidazol-4-yl}sulfanyl)azet- idine-1-carboxylate (0.31 g, 0.589 mmol) in DCM (15.0 mL) was added m-CPBA (70% in water; 0.435 g, 1.767 mmol) at 0 °C and the mixture was stirred at room temperature for 5 h. The reaction mixture was cooled to 0 °C and quenched with an aqueous solution of sodium sulfite and sodium bicarbonate (1:1). The aqueous layer was extracted with ethyl acetate (3 × 60 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO2, 0- 50% EtOAc / Hex) to yield (3-{2-[bis(3-chloro-4-fluorophenyl)methyl]-1H-imidazole-4-sulfonyl}azetidin-1-yl) tert-butyl formate (0.15 g, 45%). LCMS m / z = 502 [M+H]+. Step 3: To a stirred solution of (3-{2-[bis(3-chloro-4-fluorophenyl)methyl]-1H-imidazole-4-sulfonyl}azetidin-1- yl) tert-butyl formate (0.15 g, 0.269 mmol) was added TFA (0.21 mL, 2.686 mmol) in DCM (10.0 mL) at 0 °C and the mixture was then stirred at room temperature for 16 h. The reaction mixture was neutralized with bicar- bonate solution and extracted with ethyl acetate (2 x 30 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by reverse phase prep HPLC to obtain the title compound (0.024 g, 19%). LCMS m / z = 458 [M+H]+.1H-NMR (400 MHz, DMSO-d6): 7.85 (s, 1H), 7.49-7.47 (m, 2H), 7.38-7.28 (m, 4H), 5.68 (s, 1H), 4.33-4.29 (m, 1H), 3.78-3.74 (m, 2H), 3.60-3.56 (m, 2H). Example 182 2- 4- -4-(1-methylazetidin-3-yl)sulfonyl-1H-imidazole Step 1: To a stirred solution of 4-(azetidin-3-ylsulfonyl)-2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole (example 181, 0.17 g, 0.371 mmol) in methanol (10 mL) was added formaldehyde (37 %, 0.07 mL, 1.855 mmol) followed by addition of sodium cyanoborohydride (0.07 g, 1.113 mmol) at 0 °C. The reaction mixture was stirred at room temperature for 16 hours, quenched with a saturated aqueous solution of ammonium chloride and then 96 GRA 4216-foreign filing extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by reveres phase prep HPLC to obtain the title compound (0.045 g, 26%). LCMS m / z = 472 [M+H]+.1H-NMR (400 MHz, DMSO-d6): 13.01 (bs, 1H), 7.94 (s, 1H), 7.53-7.52 (m, 2H), 7.42-7.37 (m, 2H), 7.31-7.30 (m, 2H), 5.73 (s, 1H), 4.18-4.14 (m, 1H), 3.53-3.49 (m, 2H), 3.44-3.42 (m, 2H), 2.19 (s, 3H). Example 183 4-[[2-[bis(3-chloro-4-fluorophenyl)methyl]-1H-imidazol-4-yl]sulfonyl]piperidine Step 1: To the stirred solution of 2-[bis(3-chloro-4-fluorophenyl)methyl]-4-iodo-1H-imidazole (intermediate 4, 1.0 g, 2.15 mmol) in dioxane (30 mL) was added tert-butyl 4-sulfanylpiperidine-1-carboxylate (0.6 g, 2.58 mmol) and the mixture was degassed with argon gas for 10 min. To the mixture Pd2(dba)3(0.2 g, 0.21 mmol), Xantphos (0.3 g, 0.43 mmol) and DIPEA (1.1 mL, 6.45 mmol) were added and the mixture was heated at 100 °C in a sealed tube for 16 h. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (3 × 150 mL). The combined organic layers were washed with brine (50 mL) and dried over Na2SO4. The solvent was evaporated under reduced pressure. The obtained crude was purified by column chromatography (SiO2, 0-100% EtOAc / Hex)) to get tert-butyl 4-({2-[bis(3-chloro-4-fluorophenyl)methyl]-1H-imidazol-4-yl}sulfanyl)piperidine-1-carboxylate (1.0 g, 83%). LCMS m / z = 554 [M+H]+. Step 2: To a solution of tert-butyl 4-({2-[bis(3-chloro-4-fluorophenyl)methyl]-1H-imidazol-4-yl}sulfanyl)piperi- dine-1-carboxylate (1.0 g, 1.8 mmol) in DCM (50.0 mL) was added m-CPBA (77%, 1.3 g, 5.41 mmol) at 0 °C and the reaction mixture was stirred at 0 °C for 3 h. The reaction mixture was quenched with a mixture of sodium sulfite and sodium bicarbonate (1:1) at 0 °C. The aqueous layer was extracted with ethyl acetate (3 × 200 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified through column chromatography (SiO2, 0-100% EtOAc / Hex) to get tert-butyl 4-({2- [bis(3-chloro-4-fluorophenyl)methyl]-1H-imidazol-4-yl}sulfonyl)piperidine-1-carboxylate (0.7 g, 66%). LCMS m / z = 586 [M+H]+. Step3: To a stirred solution of tert-butyl 4-({2-[bis(3-chloro-4-fluorophenyl)methyl]-1H-imidazol-4-yl}sul- fonyl)piperidine-1-carboxylate (0.2 g, 0.34 mmol) in DCM (10 mL) was added 4M HCl in dioxane (5 mL) at 0 °C. The reaction mixture was stirred at 0 °C for 1 h and then concentrated under reduced pressure. The residue was basified with saturated NaHCO3 solution and was extracted with ethyl acetate (3 × 80 mL). The combined organic layers were washed with cold brine and dried over Na2SO4. The organic layer was concentrated under reduced pressure to get the crude product which was purified by reveres phase prep HPLC to obtain the title compound (0.048 g, 29%). LCMS m / z = 486 [M+H]+.1H-NMR (400 MHz, DMSO-d6): 7.80 (s, 1H), 7.55-7.53 97 GRA 4216-foreign filing (m, 2H), 7.41-7.30 (m, 4H), 5.70 (s, 1H), 3.14-3.11 (m, 1H), 3.00-2.97 (m, 2H), 2.44-2.41 (m, 2H), 1.78-1.75 (m, 2H), 1.42-1.38 (m, 2H). Example 184 2-[bis(3-chloro-4-fluorophenyl)methyl]-4-pyrrolidin-3-ylsulfonyl-1H-imidazole O O Step 1: In analogy to step 1 of example 1832-[bis(3-chloro-4-fluorophenyl) methyl]-4-iodo-1H-imidazole (inter- mediate 4, 1.0 g, 2.15 mmol) in dioxane (10 mL) and tert-butyl 3-sulfanylpyrrolidine-1-carboxylate (0.525 g, 2.58 mmol) were reacted to yield tert-butyl 3-({2-[bis(3-chloro-4-fluorophenyl) methyl]-1H-imidazol-4-yl} sulfanyl) pyrrolidine-1-carboxylate (0.75 g, 64%). LCMS m / z = 540 [M+H]+. Step 2: To a solution of tert-butyl 3-({2-[bis(3-chloro-4-fluorophenyl) methyl]-1H-imidazol-4-yl} sulfanyl) pyr- rolidine-1-carboxylate (0.6 g, 1.11 mmol) in DCM (20 mL) was added mCPBA (70% in water, 0.575 g, 3.33 mmol) at 0 °C and the reaction mixture was stirred at 0 °C for 2 h. The reaction mixture was quenched with a mixture of sodium sulfite and sodium bicarbonate (1:1) at 0 °C. The aqueous layer was extracted with ethyl acetate (2 × 200 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The resultant crude product was purified through column chromatography (SiO2, 0-100% EtOAc / Hex) and then chiral SFC purification (column: Chiralpak IG (30 x 250 mm) 5 m; co-solvent: Hex / MeOH / iPrOH (60 / 30 / 10), flow: 100 mL / min; % of co-solvent: 25%; ABPR: 100 bar; T: 35 °C) to yield the individual enantiomers of tert-butyl 3-({2-[bis(3-chloro-4-fluorophenyl)methyl]-1H-imidazol-4-yl}sulfonyl)pyr- rolidine-1-carboxylate. Step 3: To a stirred solution of tert-butyl-3-({2-[bis(3-chloro-4-fluorophenyl)methyl]-1H-imidazol-4-yl}sul- fonyl)pyrrolidine-1-carboxylate (first eluting enantiomer from SFC, 0.13 g, 0.22 mmol) in DCM (10 mL) was added HCl in 1,4-dioxane (4M, 10 mL) at 0 °C and the mixture was stirred at room temperature for 2 h. The reaction mixture was concentrated under reduced pressure, the crude material was quenched with NaHCO3solu- tion (30 ml) and extracted with ethyl acetate (2 x 50 mL). The combined organic layers were dried over Na2SO4and concentrated under reduced pressure. The resulting residue was purified through reverse phase prep HPLC to obtain the title compound as a single enantiomer (184b). Yield: 37% (0.04 g). Example 184a was prepared in analogy to step 3 described above, using the second eluting enantiomer from SFC as described in step 2. LCMS m / z = 472 [M+H]+.1H-NMR (400 MHz, DMSO-d6): 7.94 (s, 1H), 7.53-7.52 (m, 2H), 7.40-7.38 (m, 2H), 7.32-7.28 (m, 2H), 5.74 (s, 1H), 3.91 (bs, 1H), 3.24-3.22 (m, 2H), 2.94-2.89 (m, 2H), 2.17-2.14 (m, 1H), 2.07-2.05 (m, 1H). Chiral SFC: column: Chiralpak OX-H (4.6 x 250 mm) 5 m; co-solvent: 0.3% iPrNH2in MeOH, flow: 3 98 GRA 4216-foreign filing mL / min; % of co-solvent: 40%; ABPR: 100 bar; T: 35 °C; (184a) Rt = 2.36 min (first eluting), (184b) Rt = 2.63 min (second eluting). Example 187 (2-(bis(4-chloro-3-fluorophenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6-sulfanone Step 1: To a solution of 2-[bis(4-chloro-3-fluorophenyl)methyl]-5-methyl-4-(methylsulfanyl)-1H-imidazole (in- termediate 37, 1 g, 2.504 mmol) in DCM (20.0 mL) was added mCPBA (70% in water, 0.494 g, 2.004 mmol) at 0 °C. The reaction mixture was stirred at 0 °C for 2 h. The reaction mixture was quenched with aq. sodium bicar- bonate solution at 0 °C. The aqueous layer was extracted with ethyl acetate (100 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure to get the crude product, which was . Resulting crude was purified by column chromatography (SiO2, 0-40% EtOAc / Hex) to yield 2-[bis(4- chloro-3-fluorophenyl)methyl]-4-methanesulfinyl-5-methyl-1H-imidazole (0.75 g, 72%). LCMS m / z = 415 [M+H]+.Step 2: Iodobenzene diacetate (0.39 g, 1.205 mmol) was added to a stirred suspension of 2-[bis(4-chloro-3-fluor-ophenyl)methyl]-4-methanesulfinyl-5-methyl-1H-imidazole (0.25 g, 0.602 mmol), magnesium oxide (0.105 g, 2.59 mmol), rhodium(II) acetate dimer (0.027g, 0.06 mmol) and 2,2,2-trifluoro acetamide (0.15 g, 1.325 mmol) in 1,4-dioxane (10.0 mL) at 40 °C. The reaction mixture was stirred at 40 °C for 6 h. The reaction mixture was concentrated under reduced pressure to get the crude compound which was purified by column chromatography (SiO2, 0-60% EtOAc / Hex) to yield N-{2-[bis(4-chloro-3-fluorophenyl)methyl]-5-methyl-1H-imidazole-4-(me- thane)sulfinylidene}-2,2,2-trifluoroacetamide (0.2 g, 63%). LCMS m / z = 526 [M+H]+.Step 3: To a stirred solution of N-{2-[bis(4-chloro-3-fluorophenyl)methyl]-5-methyl-1H-imidazole-4-(me-thane)sulfinylidene}-2,2,2-trifluoroacetamide (0.6 g, 1.14 mmol) in CH3CN:MeOH (1:1, v / v) (10 mL) was added K2CO3(0.315 g, 2.28 mmol) at room temperature. The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated and diluted with ethyl acetate (50 ml). The organic layer was washed with water (20 ml) and brine (20 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure to get the crude compound which was purified by prep-HPLC to get the title compound (0.17 g, 35%). The racemic compound was separeted in the individual enantiomers using chiral HPLC. LCMS m / z = 430 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.38 (s, 1H), 7.56 (t, 2H), 7.37 (d, 2H), 7.18 (d, 2H), 5.64 (s, 1H) 3.89 (s, 1 H), 2.98 (s, 3H), 2.37 (s, 3H). Chiral HPLC: column: Chiralpak IC (4.6 x 250 mm) 5 m, mobile phase: Hexane / EtOH / iPrNH270 / 30 / 0.1, flow rate: 1.0 mL / min; 187a: Rt = 6.39 min (first eluting), 187b: Rt = 7.64 min (second eluting). 99 GRA 4216-foreign filing Example 188 (2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(methyl-d3)-1H-imidazol-4-yl)(imino)(methyl)-l6-sulfanone Step 1: A mixture of 2-[bis(3-chloro-4-fluorophenyl)methyl]-4-iodo-5-(methylsulfanyl)-1-{[2-(trimethyl- silyl)ethoxy]methyl}-1H-imidazole (intermediate 41, mixture of regioisomers, 0.84 g, 1.31 mmol) in 1,4-dioxane (8.0 mL) and water (2.0 mL) was degassed with argon for 10 min. Then, methylboranediol-D3 (0.824 g, 13.1 mmol), K3PO4(0.556 g, 2.62 mmol) and Pd(dppf)Cl2DCM (0.107 g, 0.13 mmol) was added at room temperature. The reaction mixture was heated to 110 °C for 16 h in a sealed tube. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (2 × 10 mL). The combined organic layers were washed with brine (10 mL), dried over sodium sulphate and evaporated under reduced pressure to get the crude product, which was purified by column chromatography (SiO2, 0-5% MeOH / DCM) to afford 2-[bis(3-chloro-4-fluorophenyl)methyl]-4-me- thyl-5-(methylsulfanyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole and the corresponding SEM regioiso- mer (0.12 g, 17%). LCMS m / z = 532 [M+H]+. Step 2: To a stirred solution of 2-[bis(3-chloro-4-fluorophenyl)methyl]-4-methyl-5-(methylsulfanyl)-1-{[2-(trime- thylsilyl)ethoxy]methyl}-1H-imidazole (mixture of regioisomers, 0.15 g, 0.282 mmol) in MeOH (5.0 mL) were added (NH4)2CO3(0.135 g, 1.40 mmol) and diacetoxyiodobenzene (0.45 g, 1.40 mmol). The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure to get the crude product, which was purified by column chromatography (SiO2, 0-50% EtOAc / Hex) to afford 2-[bis(3- chloro-4-fluorophenyl)methyl]-5-[imino(methane)sulfinyl]-4-methyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H- imidazole and the corresponding SEM regioisomer (0.12 g, 75%). LCMS m / z = 563 [M+H]+. Step 3: To a stirred solution of 2-[bis(3-chloro-4-fluorophenyl)methyl]-5-[imino(methane)sulfinyl]-4-methyl-1- {[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole (mixture of regioisomers, 0.4 g, 0.71 mmol) in DCM (5.0 mL) was added TFA (2.0 mL) at 0 °C and the reaction mixture was stirred at room temperature for 24 h. The reaction mixture was evaporated under reduced pressure, the residue was treated with NaHCO3solution (10 mL). The aqueous part was extracted with EtOAc (50 mL), the organic layer was washed with H2O (2 × 10 mL) and brine (2 × 10 mL). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to get the crude product, which was purified by column chromatography (SiO2, 0-60% EtOAc:EtOH (3:1) / Hex) to afford the racemic racemic title compound. The racemic compound was separeted in the individual enantiomers using chiral SFC. LCMS m / z = 433 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.38 (s, 1H), 7.53 (d, 2H), 7.39 (t, 2H), 7.33-7.30 (m, 2H), 5.62 (s, 1H), 3.89 (s, 1H), 2.97 (s, 3H). Chiral SFC: column: Chiralpak IC (4.6 x 250 mm) 5 m; co- 100 GRA 4216-foreign filing solvent: 0.3% iPrNH2in MeOH, flow: 3 mL / min; % of co-solvent: 40%; ABPR: 100 bar; T: 35 °C; (188a) Rt = 1.72 min (first eluting), (188b) Rt = 1.88 min (second eluting). Example 189 (2-(bis(3-chloro-4-fluorophenyl)methyl)-5-cyclopropyl-1H-imidazol-4-yl)(imino)(methyl)-l6-sulfanone Step 1: A solution of 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-iodo-5-(methylthio)-1-((2-(trimethylsilyl)eth-oxy)methyl)-1H-imidazole (intermediate 41, mixture of regioisomers, 500 mg, 0.78 mmol) in dioxane: water (10mL) was degassed with nitrogen for 5 min followed by the addition of cyclopropylboronic acid (336 mg, 3.89mmol), K3PO4 (500 mg, 2.34 mmol) and PdCl2(dppf) DCM (66 mg, 0.078 mmol) at room temperature. The re-sulting reaction mixture was heated to 100 °C for 16 h in a sealed tube. The reaction mixture was diluted with ethyl acetate (40 mL), washed with water (30 mL) and brine (20 mL). The organic layer was concentrated under reduced pressure to afford the crude product, which was purified by column chromatography (SiO2, 10% EtOAc / Hex) to afford 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-cyclopropyl-5-(methylthio)-1-((2-(trimethylsi- lyl)ethoxy)methyl)-1H-imidazole and the corresponding SEM regioisomer. Yield: 69% (300 mg). LCMS m / z = 555 [M+H]+. Step 2: To a stirred solution of 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-cyclopropyl-5-(methylthio)-1-((2-(tri- methylsilyl)ethoxy)methyl)-1H-imidazole (mixture of regioisomers, 700 mg, 1.26 mmol) in MeOH (18 mL) were added diacetoxyiodobenzene (1.2 g, 3.78 mmol) and ammonium carbonate (370 mg, 3.78 mmol) at room temper- ature. The resulting solution was stirred at room temperature for 3 h. The reaction mixture was diluted with ethyl acetate (40 mL), washed with water (30 mL) and brine (20 mL). The organic layer was concentrated under reduced pressure to afford (2-(bis(3-chloro-4-fluorophenyl)methyl)-4-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)- 1H-imidazol-5-yl)(imino)(methyl)-l6-sulfanone and the corresponding SEM regioisomer. Yield: Crude (700 mg). LCMS m / z = 586 [M+H]+. Step 3: To a stirred solution of (2-(bis(3-chloro-4-fluorophenyl)methyl)-4-cyclopropyl-1-((2-(trimethylsilyl)eth- oxy)methyl)-1H-imidazol-5-yl)(imino)(methyl)-l6-sulfanone (mixture of regioisomers, 700 mg, 1.19 mmol) in DCM (7 mL) was added 4 M HCl in 1,4-dioxane (14 mL) at 0 °C. The resulting solution was stirred at room temperature for 5 h. The reaction mixture was concentrated, the obtained residue was diluted with water (20 mL), basified using aqueous NaHCO3solution and extracted with ethylacetate (2 × 30 mL). The combined organic layers were washed with brine (20 mL), dried over Na2SO4and concentrated under reduced pressure to afford the crude compound, which was purified by reverse phase Prep-HPLC to afford (2-(bis(3-chloro-4-fluorophenyl)me- thyl)-4-cyclopropyl-1H-imidazol-5-yl)(imino)(methyl)-l6-sulfanone. Yield: 21% over 2 steps (120 mg). The recamic compound was separetad in the individual enantiomers using chiral SFC. 101 GRA 4216-foreign filing LCMS m / z = 456 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 11.82 (bs, 1H), 7.53 (m, 2H), 7.33 (m, 4H), 5.53 (s, 1H), 3.64 (m, 1H), 3.06 (s, 3H), 2.59 (m, 1H), 0.94 (m, 2H), 0.82 (m, 2H). Chiral SFC: column: Chiralpak IC (4.6 x 250 mm) 5 m; co-solvent: 0.3% iPrNH2 in iPrOH, flow: 3 mL / min; % of co-solvent: 40%; ABPR: 100 bar; T: 35 °C; (189a) Rt = 2.22 min (first eluting), (189b) Rt = 3.61 min (second eluting). Example 190. The title compound was prepared from the appropriate intermediates and reagents using an analogous method to that described for example 189. Example Name / Structure / Data 190a, 190b (2-(bis(3-chloro-4-fluorophenyl)methyl)-5-ethyl-1H-imidazol-4-yl)(imino)(methyl)-l6-sul- fanone LCMS m / z = 442 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.40 (bs, 1H), 7.56-7.54 (m, 2H), 7.42-7.34 (m, 4H), 5.62 (s, 1H), 3.91 (m, 1H), 2.99 (s, 3H), 2.88-2.82 (m, 2H), 1.15-1.11 (m, 3H). Chiral SFC: column: Chiralpak IC (4.6 x 250 mm) 5 m; co-solvent: 0.3% iPrNH2 in iPrOH, flow: 3 mL / min; % of co-solvent: 40%; ABPR: 1500 psi; T: 35 °C; (190a) Rt = 2.41 min (first eluting), (190b) Rt = 3.13 min (second eluting). Example 191 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-chloro-1H-imidazole-4-sulfonamide Step 1: To a solution of 2-[bis(3-chloro-4-fluorophenyl)methyl]-5-chloro-4-iodo-1H-imidazole (intermediate 19, 0.5 g, 1.002 mmol) in 1,4-dioxane (10.0 mL) was added DIPEA (0.52 mL, 3.006 mmol) at room temperature. The reaction mixture was degassed with argon for 10 min, followed by the addition of (4-methoxyphenyl)methanethiol (0.42 mL, 3.006 mmol), Xantphos (0.06 g, 0.1 mmol) and Pd2(dba)3 (0.05 g, 0.05 mmol) at room temperature. The 102 GRA 4216-foreign filing reaction mixture was heated to 110 °C for 16 h in a sealed tube. The reaction mixture was cooled to room temper- ature and filtered through a celide bed. The filtrate was evaporated under reduced pressure to get the crude product, which was purified by column chromatography (SiO2, 0-50% acetone / Hex) to afford 2-(bis(3-chloro-4-fluoro- phenyl)methyl)-5-chloro-4-((4-methoxybenzyl)thio)-1H-imidazole. Yield: 72% (0.38 g). LCMS m / z =525 [M+H]+. Step 2: To a solution of 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-chloro-4-((4-methoxybenzyl)thio)-1H-imidaz- ole (0.3 g, 0.573 mmol) in MeCN (10.0 mL) were added H2O (1.5 mL), AcOH (1.5 mL) and DCDMH (0.225 g, 1.145 mmol) at 0 °C. The reaction was stirred at 0 °C for 3 h. The reaction mixture was quenched with NaHCO3 so- lution and extracted with EtOAc. The combined organic layers were washed with water, brine, dried over Na2SO4,filtered and evaporated under reduced pressure to get the crude intermediate. The residue was dissolved in THF (10.0 mL) and 25% aq NH3 (0.5 mL) was added to the reaction mixture. The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was evaporated under reduced pressure to get the crude product, which was purified by prep HPLC to afford the title compound. Yield: 6% (0.015 g). LCMS m / z = 452 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 13.48 (bs, 1H), 7.62 (bs, 2H), 7.51 (d, 2H), 7.39 (t, 2H), 7.33-7.30 (m, 2H), 5.62 (s, 1H). Example 192 (2-(bis(3-chloro-4-fluorophenyl)methyl)-5-chloro-1H-imidazol-4-yl)(imino)(methyl)-l6-sulfanone Step 1: To a solution of 2-[bis(3-chloro-4-fluorophenyl)methyl]-4-chloro-5-iodo-1H-imidazole (intermediate 19, 1.4 g, 2.8 mmol) in 1,4-dioxane (60.0 mL) was added NaSMe (0.393 g, 5.611 mmol) at room temperature. The mixture was degassed with argon for 10 min followed by the addition of Xantphos (0.243 g, 0.421 mmol) and Pd2(dba)3 (0.257 g, 0.281 mmol) at room temperature. The reaction mixture was heated to 110 °C for 16 h in a sealed tube. The reaction mixture was cooled to room temperature and diluted with ice water. The aqueous part was extracted with ethyl acetate (3 × 80 mL). The combined organic layers were washed with brine, dried over Na2SO4and concentrated under reduced pressure to get the crude product, which was purified by column chroma- tography (SiO2, 0-50% EtOAc / Hex) to yield 2-[bis(3-chloro-4-fluorophenyl)methyl]-4-chloro-5-(methylsulfanyl)- 1H-imidazole. Yield: 59% (0.7 g). LCMS m / z = 419 [M+H]+. Step 2: To a solution of 2-[bis(3-chloro-4-fluorophenyl)methyl]-4-chloro-5-(methylsulfanyl)-1H-imidazole (0.6 g, 1.439 mmol) in DMF (10.0 mL) was added NaH (60% in mineral oil, 0.087 g, 2.15 mmol) at 0 °C and the mixture was stirred for 15 min. Then SEM-Cl (0.383 mL, 2.15 mmol, 1.5 equiv.) was added dropwise at 0 °C. The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with ice water and extracted with EA (2 × 100 mL). The combined organic layers were washed with brine (100 mL), dried over sodium sulfate 103 GRA 4216-foreign filing and evaporated under reduced pressured to get the crude product, which was purified by column chromatography (SiO2, 0-50% EtOAc / Hex) to yield 2-[bis(3-chloro-4-fluorophenyl)methyl]-4-chloro-5-(methylsulfanyl)-1-{[2- (trimethylsilyl)ethoxy]methyl}-1H-imidazole and the corresponding SEM regioisomer. Yield: 59% (0.47 g). Step 3: To a stirred solution of 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-chloro-5-(methylthio)-1-((2-(trime- thylsilyl)ethoxy)methyl)-1H-imidazole (mixture of regioisomers, 0.6 g, 1.09 mmol) in MeOH (15.0 mL) were added diacetoxyiodobenzene (1.75 g, 5.45 mmol) and ammonium carbonate (0.53 g, 5.45 mmol) at room temper- ature. The reaction mixture was diluted with EtOAc (100 mL). The mixture was diluted with ice water and ex- tracted with EA (2 × 100 mL). The combined organic part was washed with cold brine and dried over Na2SO4. The organic layer was concentrated under reduced pressure to get the crude product, which was purified by column chromatography (SiO2, 0-100% EtOAc / Hex) to get (2-(bis(3-chloro-4-fluorophenyl)methyl)-4-chloro-1-((2-(tri- methylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)(imino)(methyl)-l6-sulfanone and the corresponding SEM regioi- somer. Yield: 58% (0.370 g, 0.63 mmol). LCMS m / z = 580 [M+H]+. Step 4: To a stirred solution of {2-[bis(3-chloro-4-fluorophenyl)methyl]-4-chloro-1-{[2-(trimethylsilyl)eth-oxy]methyl}-1H-imidazol-5-yl}(imino)methyl- -sulfanone (mixture of regioisomers, 0.4 g, 0.688 mmol) in ethylacetate (10.0 mL) was added 4M HCl in dioxane (12.0 mL) at room temperature. The reaction mixture was stirred at room temperature for 4 h. The reaction mixture was concentrated under reduced pressure to obtain a residue, which was diluted with water and neutralized with NaHCO3solution. The aqueous part was extacted with ethyl acetate. The combined organic layers were washed with cold brine, dried over Na2SO4and concentrated under reduced pressure to get the crude product, which was purified by column chromatography (SiO2, 0-100% EtOAc / Hex) to yield the racemic title compound. The racemic compound was separetad in the individual enantiomers using chiral SFC. Yield: 192a = 15% (0.047 g), 192b = 9% (0.029 g). LCMS m / z = 450 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 13.42 (s, 1H), 7.55-7.52 (m, 2H), 7.42-7.34 (m, 4H), 5.64 (s, 1H), 4.74 (s, 1H), 3.12 (s, 3H). Chiral SFC: column: Chiralcel OX-H (4.6 x 250 mm) 5 m; co-solvent: 0.3% iPrNH2 in MeCN / iPrOH (1:1), flow: 3 mL / min; % of co- solvent: 40%; ABPR: 1000 psi; T: 35 °C; (192a) Rt = 1.67 min (first eluting), (192b) Rt = 2.25 min (second eluting). Example 193 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(methoxymethyl)-4-(methylsulfonyl)-1H-imidazole F Cl F Step 1: To a solution of 2-[bis(3-chloro-4-fluorophenyl)methyl]-4-iodo-5-methanesulfonyl-1H-imidazole (inter- mediate 13, 0.4 g, 0.737 mmol) in DCM (15 mL) was added DIPEA (0.5 g, 2.94 mmol) at room temperature and the mixture was stirred for 15 min. Then SEM-Cl (0.4 mL, 2.21 mmol) was added dropwise to reaction mixture. 104 GRA 4216-foreign filing The reaction mixture was stirred at 40 °C for 16 h. The reaction mixture was diluted with ice water and extracted with ethyl acetate (2 × 100 mL). The comined organic layers were washed with brine (50 mL), dried over sodium sulfate and evaporated under reduced pressure to get the crude compound, which was purified by column chroma- tography (SiO2, 0-50% EtOAc / Hex) to yield 2-[bis(3-chloro-4-fluorophenyl)methyl]-4-iodo-5-methanesulfonyl- 1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole and the corresponding SEM regioisomer. Yield: 54% (0.27 g) Step 2: To a solution of 2-[bis(3-chloro-4-fluorophenyl)methyl]-5-iodo-4-methanesulfonyl-1-{[2-(trimethylsi- lyl)ethoxy]methyl}-1H-imidazole (mixture of regioisomers, 0.3 g, 0.445 mmol) in 1,4-dioxane-H2O (20 mL) were added K2CO3 (0.123 g, 0.891 mmol) and potassium vinyltrifluoroborate (0.120 g, 0.891 mmol) at room tempera- ture. The reaction mixture was degassed with argon for 10 minutes. Then PdCl2(dppf) (0.033 g, 0.045 mmol) was added and the mixture was heated to 110 °C for 16 h in a sealed tube. The mixture was cooled down to room temperature. The reaction mixture was extracted with ethyl acetate (2 × 100 mL). The Combined organic layerS were washed with brine, dried over Na2SO4 and concentrated under reduced pressure to get crude product, which was purified by column chromatography (SiO2, 0-60% EtOAc / Hex) to yield 2-[bis(3-chloro-4-fluorophenyl)me- thyl]-5-ethenyl-4-methanesulfonyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole and the corresponding SEM regioisomer. Yield: 39% (0.12 g). LCMS m / z = 573 [M+H]+. Step 3: To a stirred solution of 2-[bis(3-chloro-4-fluorophenyl)methyl]-5-ethenyl-4-methanesulfonyl-1-{[2-(tri- methylsilyl)ethoxy]methyl}-1H-imidazole (mixture of regioisomers, 0.8 g, 1.39 mmol) in dioxane (15 mL) and H2O (5 mL) were added 0.16 M OsO4in H2O (0.3 mL, 0.042 mmol) and NMO (50%, 0.360 g, 1.53 mmol) at room temperature. The reaction was stirred at room temperature for 16 h. Then NaIO4 (3.0 g, 13.94 mmol) was added to the reaction mixture and the mixtue was stirred at room temperature for 1 h. The reaction mixture was diluted with water (30 mL) and extracted with ethyl acetate (3×100 mL). The combined organic layers were dried over anhyd. Na2SO4and concentrated under reduced pressure to get crude product, which was purified by column chromatography (SiO2, 0-70% EtOAc / Hex) to get 2-[bis(3-chloro-4-fluorophenyl)methyl]-4-methanesulfonyl-1- {[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole-5-carbaldehyde and the corresponding SEM regioisomer. Yield: 49% (0.400 g). Step 4: To a stirred solution of 2-[bis(3-chloro-4-fluorophenyl)methyl]-4-methanesulfonyl-1-{[2-(trimethylsi- lyl)ethoxy]methyl}-1H-imidazole-5-carbaldehyde (mixture of regioisomers, 0.45 g, 0.782 mmol) in MeOH (8 mL) was added NaBH4 (0.149 g, 3.909 mmol) portionwise at 0 °C. The reaction mixture was stirred at room temperature for 4 h. The reaction mixture was cooled to 0 °C and diluted with water. The aqueous part was extracted with ethyl acetate (2 × 100 mL). The combined organic layers were washed with brine and dried over anhyd. Na2SO4. The organic layer was concentrated under reduced pressure to get the crude product, which was purified by column chromatography (SiO2, 0-70% EtOAc / Hex) to get {2-[bis(3-chloro-4-fluorophenyl)methyl]-4-methanesulfonyl-1- {[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-5-yl}methanol and the corresponding SEM regioisomer. Yield: 55% (0.25 g). Step 5: To a solution of {2-[bis(3-chloro-4-fluorophenyl)methyl]-4-methanesulfonyl-1-{[2-(trimethylsilyl)eth- oxy]methyl}-1H-imidazol-5-yl}methanol (mixture of regioisomers, 0.13 g, 0.225 mmol) in THF (2.0 mL) were added Ag2O (0.107 g, 0.45 mmol) and MeI (4.0 mL) at room temperature. The reaction mixture was heated to 50 °C for 16 h in a sealed vial. The reaction mixture was diluted with ethyl acetate and filtered through a celite bed. The filtrate was evaporated under reduced pressure, the obtained residue was purified by column chromatography 105 GRA 4216-foreign filing (SiO2, 0-50% EtOAc / Hex) to get 2-[bis(3-chloro-4-fluorophenyl)methyl]-4-methanesulfonyl-5-(methoxymethyl)- 1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole and the corresponding SEM regioisomer. Yield: 52% (0.07 g). LCMS m / z = 591 [M+H]+. Step 6: A solution of 2-[bis(3-chloro-4-fluorophenyl)methyl]-4-methanesulfonyl-5-(methoxymethyl)-1-{[2-(tri- methylsilyl)ethoxy]methyl}-1H-imidazole (mixture of regioisomers, 0.1 g, 0.169 mmol) in acetic acid (0.5 mL) and H2O (0.2 mL) was heated to 50 °C for 4 h. The reaction mixture was diluted with water and neutralized with aq. NaHCO3 solution. The aqueous part was extacted with ethyl acetate (2 x 20 mL). The combined organic laxerswere washed with cold brine, dried over Na2SO4 and concentrated under reduced pressure. The obtained residuewas purified by reverse phase prep HPLC to get the title compound. Yield: 37% (0.029 g). LCMS m / z = 461 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 13.03 (s, 1H), 7.54 (m, 2H), 7.42-7.38 (m, 2H), 7.33 (s, 2H), 5.69 (s, 1H), 4.60 (s, 2 H), 3.32-3.27 (m, 3H), 3.11 (s, 3H). Example 194 6-(bis(3-chloro-4-fluorophenyl)methyl)-4-methyl-2,5-dihydroimidazo[4,5-e][1,2]thiazine 1,1-dioxide Step 1: To a solution of 2-[bis(3-chloro-4-fluorophenyl)methyl]-5-iodo-4-{[(4-methoxyphenyl)methyl]sulfanyl}- 1H-imidazole (intermediate 42, 1.0 g, 1.62 mmol) in MeCN (10.0 mL), AcOH (0.8 mL) and H2O (0.4 mL) was added DCDMH (0.64 g, 3.25 mmol) at 0 °C. The reaction mixture was stirred at room temperature for 1.5 h. The reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and evaporated under reduced pressure to get the crude product. The crude product was dissolved in DCM (10 mL) followed by the addition of TEA (0.7 mL, 4.87 mmol) and allyl amine (0.6 mL, 8.11 mmol) at 0 °C. Reaction mixture was stirred for 1.5 h at room temperature. The reaction mixture was quenched with ice water and extracted with ethyl acetate (3× 50 mL). The combined organic layers were dried over anhydrous sodium sulphate and evaporated under reduced presure to get the crude product, which was purified by column chromatography (SiO2, 0-60% EtOAc / Hex) to yield N-allyl-2-(bis(3-chloro-4-fluoro- phenyl)methyl)-5-iodo-1H-imidazole-4-sulfonamide. Yield: 42% (0.4 g). LCMS m / z = 584 [M+H]+. Step 2: To a stirred solution of N-allyl-2-(bis(3-chloro-4-fluorophenyl)methyl)-5-iodo-1H-imidazole-4-sulfona- mide (0.4 g, 0.68 mmol) in DMF (5 mL) was added TEA (0.3 mL, 2.06 mmol) and the mixture was degassed with argon for 10 min. Then bis(tri-tert-butylphosphine)palladium(0) (0.035 g, 0.069 mmol) was added to the reaction mixture at room temperature. The reaction mixture was heated to 100 °C in a sealed tube for 16 h. The reaction mixture was filtered through a celite bed. The filtrate was evaporated under reduced pressure to get the crude product, which was purified by prep HPLC to yield 6-(bis(3-chloro-4-fluorophenyl)methyl)-4-methyl-2,5-dihy- droimidazo[4,5-e][1,2]thiazine 1,1-dioxide. Yield: 5% (0.015 g). 106 GRA 4216-foreign filing LCMS m / z = 456 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.90 (s, 1H), 10.76 (s, 1H), 7.55 (d, 2H), 7.43-7.39 (m, 2H), 7.33 (bs, 2H), 6.49 (s, 1H), 5.73 (s, 1H), 2.10 (s, 3H). Example 195 7-(bis(3-chloro-4-fluorophenyl)methyl)-3,6-dihydro-2H-imidazo[4,5-f][1,2]thiazepine 1,1-dioxide O H F Cl Step 1: To a solution of 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-iodo-4-((4-methoxybenzyl)thio)-1H-imidazole (intermediate 42, 1.5 g, 2.43 mmol) in 1,4-dioxane-H2O (10:1, 75 mL) were added K2CO3(0.675 g, 4.86 mmol) and potassium vinyltrifluoroborate (0.655 g, 4.86 mmol) at room temperature. The reaction mixture was degassed with argon for 10 min, followed by the addition of PdCl2(dppf) (0.18 g, 0.243 mmol) at room temperature. The reaction mixture was heated to 110 °C for 16 h in a sealed tube. The reaction mixture was cooled to room temper- ature, diluted with ethyl acetate and filtered through a celite bed. The filtrate was evaporated under reduced pres- sure, the resulting residue was purified by column chromatography (SiO2, 0-50% EtOAc / Hex) to yield 2-(bis(3- chloro-4-fluorophenyl)methyl)-4-((4-methoxybenzyl)thio)-5-vinyl-1H-imidazole. Yield: 55% (0.7 g). LCMS m / z = 517 [M+H]+. Step 2: To a solution of 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-((4-methoxybenzyl)thio)-5-vinyl-1H-imidazole (0.7 g, 1.353 mmol) in MeN (18.0 mL)-AcOH (1.5 mL)-H2O (0.9 mL) was added DCDMH (0.535 g, 2.706 mmol) at 0 °C. The reaction was stirred at 0 °C for 2 h. The reaction mixture was diluted with ethyl acetate and quenched with cold sat. NaHCO3 solution. The organic layer was separated, washed with brine, dried over Na2SO4 and con- centrated under reduced pressure to get crude product. The crude product was dissolved in DCM (15.0 mL). To the solution were added TEA (0.6 mL, 4.056 mmol) and prop-2-en-1-amine (0.21 mL, 2.704 mmol) at 0 °C and the reaction mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with ice water and extracted with ethyl acetate (2 x 80 mL). The combined organic layers were washed with brine, dried over sodium sulphate and concentrated under reduced pressure. The resulting crude product was purified by column chromatography (SiO2, 0-50% EtOAc / Hex) to yield N-allyl-2-(bis(3-chloro-4-fluorophenyl)methyl)-5-vinyl-1H- imidazole-4-sulfonamide. Yield: 42% (0.28 g) over two steps. LCMS m / z = 484 [M+H]+. Step 3: A stirred solution of N-allyl-2-(bis(3-chloro-4-fluorophenyl)methyl)-5-vinyl-1H-imidazole-4-sulfonamide (0.48 g, 0.991 mmol) in DCM (60 mL) was degassed with argon gas for 5 minutes, followed by the addition of Grubbs catalyst, 2nd generation (0.59 g, 0.694 mmol) at room temperature. The reaction mixture was stirred at room temperature for 3 days in a sealed tube. The reaction mixture was concentrated under reduced pressure, the residue was purified by reveres phase prep HPLC to yield the title compound. Yield: 3% (0.013 g). LCMS m / z = 456 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.66 (s, 1H), 7.65-7.54 (m, 1H), 7.53-7.51 (m, 2H), 7.42 (t, 2H), 7.32-7.29 (m, 2H), 6.43 (d, 1H), 6.00-5.91 (m, 1H), 5.70 (s, 1H), 3.89-3.86 (m, 2H). 107 GRA 4216-foreign filing Example 196 7-(bis(3-chloro-4-fluorophenyl)methyl)-3,4,5,6-tetrahydro-2H-imidazo[4,5-f][1,2]thiazepine 1,1-dioxide Step 1: To a solution of 2-[bis(3-chloro-4-fluorophenyl)methyl]-5-ethenyl-N-(prop-2-en-1-yl)-1H-imidazole-4- sulfonamide (0.04 g, 0.826 mmol) in DCM (15.0 mL) was added DIPEA (0.45 mL, 2.478 mmol) followed by the dropwise addition of SEM-Cl (0.2 mL, 1.074 mmol) at 0 °C. The reaction mixture was stirred at 40 °C for 16 h. The reaction mixture was quenched with saturated ammonium chloride and extracted with DCM (2 x 20 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure to obtain the crude product, which was purified by column chromatography (SiO2, 0-40% EtOAc / Hex) to obtain N-allyl-2-(bis(3-chloro-4-fluorophenyl)methyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-5-vinyl-1H-imid- azole-4-sulfonamide and the corresponding SEM regioisomer. Yield: 49% (0.25 g). LCMS m / z = 614 [M+H]+. Step 2: A solution of N-allyl-2-(bis(3-chloro-4-fluorophenyl)methyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-5-vi- nyl-1H-imidazole-4-sulfonamide (mixture of regioisomers, 0.25 g, 0.407 mmol) in DCM (100 mL) was degassed with argon gas for 10 minutes followed by the addition of Grubbs catalyst, 2nd gen (0.245 g, 0.285 mmol) at room temperature. The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure, the resulting crude was purified by column chromatography (SiO2, 0-50% EtOAc / Hex) to obtain 7-(bis(3-chloro-4-fluorophenyl)methyl)-6-((2-(trimethylsilyl)ethoxy)methyl)-3,6-dihydro-2H-imidazo- [4,5-f][1,2]thiazepine 1,1-dioxide (mixture of regioisomers). Yield: 49% (0.238 g). LCMS m / z = 586 [M+H]+. Step 3: A solution of 7-(bis(3-chloro-4-fluorophenyl)methyl)-6-((2-(trimethylsilyl)ethoxy)methyl)-3,6-dihydro- 2H-imidazo[4,5-f][1,2]thiazepine 1,1-dioxide (mixture of regioisomers, 0.238 g, 0.406 mmol) in MeOH (15.0 mL) was degassed with nitrogen gas for 5 min followed by the addition of PtO2 (0.06 g) at room temperature. The reaction mixture was stirred at room temperature for 4 h under H2 balloon pressure. The reaction mixture was filtered through a celite bed and the filtrate was concentrated under reduced pressure to obtain 7-(bis(3-chloro-4- fluorophenyl)methyl)-6-((2-(trimethylsilyl)ethoxy)methyl)-3,4,5,6-tetrahydro-2H-imidazo[4,5-f][1,2]thiazepine 1,1-dioxide (mixture of regioisomers). Yield: 96% (0.23 g). LCMS m / z = 588 [M+H]+. Step 4: To a stirred solution of 7-(bis(3-chloro-4-fluorophenyl)methyl)-6-((2-(trimethylsilyl)ethoxy)methyl)- 3,4,5,6-tetrahydro-2H-imidazo[4,5-f][1,2]thiazepine 1,1-dioxide (mixture of regioisomers) (0.230 g, 0.391 mmol) in DCM (5.0 mL) was added 4(M) HCl in dioxane (10.0 mL) at 0 °C. The reaction mixture was stirred at room temperature for 6 h. The reaction mixture was concentrated under reduced pressure, the resulting residue was neu- tralized with NaHCO3 solution and extracted with ethyl acetate (2×100 mL). The combined organic layera were 108 GRA 4216-foreign filing washed with brine, dried over Na2SO4and concentrated under reduced pressure. The residue was purified by re- verse phase prep HPLC to yield the title compound. Yield: 30% (0.055 g). LCMS m / z = 456 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.40 (bs, 1H), 7.52 (d, 2H),7.43-7.38 (m, 3H), 7.37- 7.27 (m, 2H), 5.61 (s, 1H), 3.27-2.25 (m, 2H), 2.79-2.76 (m, 2H), 1.77-1.76 (m, 2H). Example 197 2-(bis(3-chloro-4-fluorophenyl)methyl)-5,6,7,8-tetrahydro-1H-thiepino[2,3-d]imidazole 4,4-dioxide O F Cl Step 1: A solution of 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H- imidazole (intermediate 5, mixture of regioisomers) (1.4 g, 2.348 mmol) and but-3-yn-1-ol (1.32 g, 18.781 mmol) in DMSO (20 mL) was degassed with argon for 10 minutes followed by the addition of diethyl amine (1.5 mL, 14.086 mmol), CuI (0.09 g, 0.47 mmol) and Pd(PPh3)4(0.271 g, 0.235 mmol) at room temperature. The reaction mixture was heated to 90 °C for 16 h in a sealed tube. The mixture was colled to ropom temperature and filtered through celite. The filtrate was concentrated under reduced pressure, the resulting crude was purified by column chromatography (SiO2, 0-50% EtOAc / Hex) to get 4-(2-(bis(3-chloro-4-fluorophenyl)methyl)-1-((2-(trimethylsi- lyl)ethoxy)methyl)-1H-imidazol-5-yl)but-3-yn-1-ol (mixture of regioisomers). Yield: 87% (1.1 g). LCMS m / z = 537 [M+H]+. Step 2: To a solution of 4-(2-(bis(3-chloro-4-fluorophenyl)methyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imid- azol-5-yl)but-3-yn-1-ol (mixture of regioisomers, 1.3 g, 2.414 mmol) in methanol (30 mL) was added PtO2 (0.26 g). The reaction mixture was stirred at room temperature under H2-balloon pressure for 5 h. The reaction mixture was filtered through a celite bed, the celite bed was washed with methanol and the filtrate was concentrated under reduced pressure to afford 4-(2-(bis(3-chloro-4-fluorophenyl)methyl)-1-((2-(trimethylsilyl)ethoxy)methyl)- 1H-imidazol-5-yl)butan-1-ol (mixture of regioisomers). Yield: 92% (1.2 g). LCMS m / z = 541 [M+H]+. Step 3: To a stirred solution of 4-(2-(bis(3-chloro-4-fluorophenyl)methyl)-1-((2-(trimethylsilyl)ethoxy)methyl)- 1H-imidazol-5-yl)butan-1-ol (mixture of regioisomers, 1.45 g, 2.673 mmol) in DMF (30 mL) was added NIS (2.4 g, 10.69 mmol). The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was quenched with saturated sodium thiosulphate solution and extracted with EtOAc (3 x 300 mL). The combined organic layers were washed with brine (100 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by coloumn chromatography (SiO2, 0-40% EtOAc / Hex) to yield 4-(2-(bis(3-chloro- 4-fluorophenyl)methyl)-4-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)butan-1-ol (mixture of re- gioisomers). Yield: 67% (1.2 g). LCMS m / z = 667 [M+H]+. 109 GRA 4216-foreign filing Step 4: To a solution of 4-(2-(bis(3-chloro-4-fluorophenyl)methyl)-4-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)- 1H-imidazol-5-yl)butan-1-ol (mixture of regioisomers, 1.0 g, 1.496 mmol) in DCM (50 mL) were added TEA (0.7 mL, 4.488 mmol) and MsCl (0.2 mL, 2.244 mmol) at 0 °C. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with ice water and the resulting mixture was extracted with DCM (2 × 300 mL). The combined organic layers were dried over Na2SO4and concentrated under reduced pressure to afford 4-(2-(bis(3-chloro-4-fluorophenyl)methyl)-4-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)butyl methanesulfonate (mixture of regioisomers). Yield: Crude (1.1 g). LCMS m / z = 745 [M+H]+. Step 5: To a solution 4-(2-(bis(3-chloro-4-fluorophenyl)methyl)-4-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H- imidazol-5-yl)butyl methanesulfonate (mixture of regioisomers, 1.0 g, 1.34 mmol) in MeCN (20 mL) was added 1- (potassiosulfanyl)ethan-1-one (0.306 g, 2.679 mmol) at room temperature and the reaction was stirred at room temperature for 16 h. The reaction mixture was diluted with water and extracted with EtOAc (2 x 300 mL). The combined organic layers were washed with brine, dried over sodium sulphate and concentrated under reduced pressure. The resulting crude product was purified by column chromatography (SiO2, 0-30% EtOAc / Hex) to obtain S-(4-(2-(bis(3-chloro-4-fluorophenyl)methyl)-4-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)bu- tyl) ethanethioate (mixture of regioisomers). Yield: 49% (0.48 g). LCMS m / z = 725 [M+H]+. Step 6: To a solution of S-(4-(2-(bis(3-chloro-4-fluorophenyl)methyl)-4-iodo-1-((2-(trimethylsilyl)ethoxy)me- thyl)-1H-imidazol-5-yl)butyl) ethanethioate (mixture of regioisomers, 0.3 g, 0.413 mmol) in MeOH (20 mL) was added NaSMe (0.03 g, 0.413 mmol) at 0 °C and the reaction mixture was stirred at 0 °C for 2 h. The reaction mixture was diluted with ice cold water and extracted with EtOAc (2 x 15 mL). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by column chro- matography (SiO2, 0-40% EtOAc / Hex) to obtain 4-(2-(bis(3-chloro-4-fluorophenyl)methyl)-4-iodo-1-((2-(trime- thylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)butane-1-thiol (mixture of regioisomers). Yield: 36% (0.18 g). LCMS m / z = 683 [M-H]-. Step 7: A solution of 4-(2-(bis(3-chloro-4-fluorophenyl)methyl)-4-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H- imidazol-5-yl)butane-1-thiol (mixture of regioisomers, 0.18 g, 0.263 mmol) in 1,4-dioxane (3 mL) was degassed with argon gas for 10 min followed by the addition of Pd2(dba)3(0.025 g, 0.026 mmol), Xantphos (0.031 g, 0.053 mmol) and DIPEA (0.15 mL, 0.789 mmol) at room temperature. The mixture was then heated to 80 °C for 16 h. The reaction mixture was diluted with water and extracted with EtOAc (2x 15 mL). The combined organic layers were dried over Na2SO4and concentrated. The residue was purified by column chromatography (SiO2, 0-15% EtOAc / Hex) to obtain 2-(bis(3-chloro-4-fluorophenyl)methyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-5,6,7,8-tetra- hydro-1H-thiepino[2,3-d]imidazole (mixture of regioisomers). Yield: 47% (0.07 g). LCMS m / z = 553 [M+H]+. Step 8: To a solution of 2-(bis(3-chloro-4-fluorophenyl)methyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-5,6,7,8-tet- rahydro-1H-thiepino[2,3-d]imidazole (mixture of regioisomers, 0.07 g, 0.126 mmol) in DCM (15 mL) was added mCPBA (0.045 g, 0.252 mmol) at room temperature and the mixture was stirred at room temperature for 3 h.The reaction mixture was quenched with sat. aqueous sodium thiosulphate solution and stirred for 30 min. The layers were separated, the organic layer was dried over Na2SO4 and concentrated to get the crude compound, which was purified by column chromatography (SiO2, 0-30% EtOAc / Hex) to obtain 2-(bis(3-chloro-4-fluorophenyl)me- thyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-5,6,7,8-tetrahydro-1H-thiepino[2,3-d]imidazole 4,4-dioxide (mixture of regioisomers). Yield: 68 % (0.05 g). LCMS m / z = 587 [M-H]-. 110 GRA 4216-foreign filing Step 9: To a solution of 2-(bis(3-chloro-4-fluorophenyl)methyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-5,6,7,8-tet- rahydro-1H-thiepino[2,3-d]imidazole 4,4-dioxide (mixture of regioisomers, 0.05 g, 0.085 mmol) in DCM (5 mL) was added 4M HCl in 1,4-dioxane (1 mL) at room temperature and the mixture was stirred at room tempera- ture for 3 h. The reaction mixture was concentrated under redued pressure, the obtained residue was purified by reverse phase prep HPLC to obtain the title compound. Yield: 33% (0.013 g) LCMS m / z = 457 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.55 (bs, 1H), 7.54-7.51 (m, 2H), 7.42-7.38 (m, 2H), 7.33-7.21 (m, 2H), 5.63 (s, 1H), 3.28-3.27 (m, 2H), 2.78-2.75 (m, 2H), 2.07 (m, 2H), 1.74 (m, 2H). Example 198 N-((2-(bis(3-chloro-4-fluorophenyl)methyl)-4-methyl-1H-imidazol-5-yl)methyl)methanesulfonamide Step 1: To a solution of 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-iodo-5-methyl-1-((2- (trimethylsilyl)ethoxy)methyl)-1H-imidazole (intermediate 43, mixture of regioisomers, 9 g, 14.77 mmol) in MeOH (120 mL) was added TEA (5.1 mL, 36.93 mmol) at room temperature. The reaction mixture was degassedwith argon for 10 min followed by the addition of PdCl2(dppf) DCM (0.6 g, 0.74 mmol). The resulting reactionmixture was heated to 90°C under 10 bar pressure of CO gas for 16 h. The reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (2 × 160 mL). The combined organic layers were washed with brine (90 mL), dried over Na2SO4 and concentrated under reduced pressure to afford the crude product, which was purified by column chromatography (SiO2, 30% EtOAc / Hex) to afford methyl 2-(bis(3-chloro-4-fluorophenyl)methyl)-5- methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-4-carboxylate and the corresponding SEM regioiso- mer. Yield: 78% (6.2 g). LCMS m / z = 541 [M+H]+. Step 2: To a stirred solution of methyl 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-methyl-1-((2-(trimethylsilyl)eth- oxy)methyl)-1H-imidazole-4-carboxylate (mixture of regioisomers, 3 g, 5.54 mmol) in THF (30 mL) was added LiBH4(2 M in THF, 16.6 mL, 33.24 mmol) dropwise at 0 °C. The resulting reaction mixture was stirred at room temperature for 16 h. The reaction mixture was quenched with ammonium chloride (120 mL) and was extracted with ethyl acetate (2 × 150 mL). The combined organic layers were washed with brine (90 mL), dried over Na2SO4 and concentrated under reduced pressure to afford the crude product, which was purified by column chromatog- raphy (SiO2, 50% EtOAc / Hex) to afford (2-(bis(3-chloro-4-fluorophenyl)methyl)-5-methyl-1-((2-(trimethylsi- lyl)ethoxy)methyl)-1H-imidazol-4-yl)methanol and the corresponding SEM regioisomer. Yield: 70% (2 g). LCMS m / z = 513 [M+H]+. Step 3: To a stirred solution of (2-(bis(3-chloro-4-fluorophenyl)methyl)-5-methyl-1-((2-(trimethylsilyl)eth- oxy)methyl)-1H-imidazol-4-yl)methanol (mixture of regioisomers, 1 g, 1.95 mmol) in toluene (25 mL) was added DPPA (0.6 mL, 2.92 mmol) followed by DBU (0.45 mL, 2.92 mmol) at room temperature. The resulting reaction mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with cold water (60 mL) and 111 GRA 4216-foreign filing extracted with ethyl acetate (2 × 70 mL). The combined organic layers were washed with brine (70 mL), dried over Na2SO4and concentrated under reduced pressure to afford the crude product, which was purified by column chromatography (SiO2, 10% EtOAc / Hex) to afford 4-(azidomethyl)-2-(bis(3-chloro-4-fluorophenyl)methyl)-5- methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole and the corresponding SEM regioisomer. Yield: 66% (0.7 g). LCMS m / z = 538 [M+H]+. Step 4: To a stirred solution of 4-(azidomethyl)-2-(bis(3-chloro-4-fluorophenyl)methyl)-5-methyl-1-((2-(trime- thylsilyl)ethoxy)methyl)-1H-imidazole (mixture of regioisomers, 0.7 g, 1.29 mmol) in THF:water (25 mL, 4:1) was added PPh3 (0.5 g, 1.95 mmol) at 0 °C. The resulting reaction mixture was stirred at room temperature for 16 h. The mixture was quenched with cold water (20 mL) and was extracted with ethyl acetate (2 × 80 mL). The combined organic layers were washed with brine (60 mL), dried over anhydrous Na2SO4and concentrated under reduced pressure to afford the crude product, which was purified by column chromatography (SiO2, 5% MeOH / DCM) to afford (2-(bis(3-chloro-4-fluorophenyl)methyl)-5-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)- 1H-imidazol-4-yl)methanamine and the corresponding SEM regioisomer. Yield: 76% (0.5 g). LCMS m / z = 512 [M+H]+. Step 5: To a stirred solution of (2-(bis(3-chloro-4-fluorophenyl)methyl)-5-methyl-1-((2-(trimethylsilyl)eth- oxy)methyl)-1H-imidazol-4-yl)methanamine (mixture of regioisomers, 0.4 g, 0.78 mmol) in DCM (8 mL) was added TEA (0.27 mL, 1.95 mmol) followed by mesyl chloride (0.07 mL, 0.94 mmol) at 0 °C. The resulting reaction mixture was stirred at room temperature for 2 h. Ther reaction mixture was quenched with cold water (20 mL) and was extracted with DCM (2 × 30 mL). The combined organic layers were washed with brine (30 mL), dried over Na2SO4 and concentrated under reduced pressure to afford the crude product, which was purified by column chro- matography (SiO2, 30% EtOAc / Hex) to afford N-((2-(bis(3-chloro-4-fluorophenyl)methyl)-5-methyl-1-((2-(tri- methylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)methyl)methanesulfonamide and the corresponding SEM regioiso- mer . Yield: 65% (0.3 g). LCMS m / z = 590 [M+H]+. Step 6: To a stirred solution of N-((2-(bis(3-chloro-4-fluorophenyl)methyl)-5-methyl-1-((2-(trimethylsilyl)eth- oxy)methyl)-1H-imidazol-4-yl)methyl)methanesulfonamide (mixture of regioisomers, 0.3 g, 0.51 mmol) in DCM (3 mL) was added TFA (6 mL) at 0 °C. The resulting solution was stirred at room temperature for 16 h. The reactionmixture was concentrated, the obtained residue was diluted with water, basified using NaHCO3solution and extracted with ethyl acetate (2 × 30 mL). The combined organic layers were washed with brine, dried over Na2SO4and concentrated under reduced pressure to afford the crude product, which was purified by reverse phase prep-HPLC to afford the title compound. Yield: 43% (0.1 g). LCMS m / z = 460 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 11.43 (s, 1H), 7.50-7.48 (m, 2H), 7.31-7.29 (m, 4H), 6.80 (bs, 1H), 5.52 (s, 1H), 4.03 (m, 2H), 2.87 (s, 3H), 2.14 (s, 3H). 112 GRA 4216-foreign filing Example 199 3-chloro-6-((4-chlorophenyl)(4-(methylsulfonyl)-1H-imidazol-2-yl)methyl)-2-(trifluoromethyl)pyridine To a solution of 3-chloro-6-[(4-chlorophenyl) [4-(methylsulfanyl)-1H-imidazol-2-yl] methyl]-2-(trifluoromethyl) pyridine (intermediate 44, 0.3 g, 0.718 mmol) in DCM (5.0 mL) was added mCPBA (77%, 0.482 g, 2.153 mmol) at room temperature. The reaction mixture was stirred for 3 h. The reaction mixture was basified with saturated Na2SO3 solution, stirred for 30 minutes and extracted with ethyl acetate (3 × 50 mL). The combined organic layers were washed with brine, dried over Na2SO4and concentrated under reduced pressure to get the crude product, which was purified by column chromatography (SiO2, EtOAc) ans later HPLC to get the title compound. Yield: 5% (0.016 g). LCMS m / z = 450 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 8.25 (d, 1H), 7.82 (s, 1H), 7.75 (d, 1H), 7.43 (d, 2H), 7.36 (d, 2H), 5.90 (s, 1H), 3.07 (s, 3H). Example 200 (2-((5-chloro-6-(trifluoromethyl)pyridin-2-yl)(4-chlorophenyl)methyl)-1H-imidazol-4-yl)(imino)(methyl)-l6- sulfanone Step 1: To a solution of 3-chloro-6-[(4-chlorophenyl)[4-(methylsulfanyl)-1H-imidazol-2-yl]methyl]-2- (trifluoromethyl)pyridine (intermediate 44, 300 mg, 0.717 mmol) in DMF (10 mL) was added NaH (57 mg, 1.435 mmol) at 0 °C. The mixture was stirred at room temperature for 30 min. Then SEM-Cl (0.18 g, 1.076 mmol) was added at 0 °C, the mixture was then stirred at room temperature overnight. The mixture was then quenched with crushed ice and extracted with ethyl acetate (3x 50 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and cocentrated under reduced pressure to get the crude product which was purified by column chromatography (SiO2, 5% EtOAc / Hex) to get 3-chloro-6-[(4-chlorophenyl)[4-(methylsulfanyl)-1-{[2- (trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]methyl]-2-(trifluoromethyl)pyridine and the corresponding SEM regioisomer. Yield: 33% (0.13 g). LCMS m / z = 548 [M+H]+. 113 GRA 4216-foreign filing Step 2: To a stirred solution of 3-chloro-6-[(4-chlorophenyl)[4-(methylsulfanyl)-1-{[2-(trimethylsilyl)ethoxy]me- thyl}-1H-imidazol-2-yl]methyl]-2-(trifluoromethyl)pyridine (mixture of regioisomers, 0.22 g, 0.401 mmol) in MeOH (3 mL) were added diacetoxyiodobenzene (0.65 g, 2.005 mmol) and ammonium carbonate (0.19 g, 2.005 mmol) at room temperature. The mixcture was then stirred for 2 h. The solvent was evaporated under reduced pressure (without heating) to get the crude product, which was purified by column chromatography to get 3-chloro- 6-[(4-chlorophenyl)({4-[imino(methane)sulfinyl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl})me- thyl]-2-(trifluoromethyl)pyridine and the corresponding SEM regioisomer. Yield: Crude (0.12 g, 0.21 mmol) Step 3: To a stirred solution of 3-chloro-6-[(4-chlorophenyl)({4-[imino(methane)sulfinyl]-1-{[2-(trimethylsi- lyl)ethoxy]methyl}-1H-imidazol-2-yl})methyl]-2-(trifluoromethyl)pyridine (mixture of regioisomers, 0.12 g, 0.207 mmol) in DCM (2 mL) was added 4M HCl in dioxane (0.5 mL, 2.071 mmol) at 0 °C. The mixture was then stirred at room temperature for 4 h. The solvent was evaporated to get the crude product which was purified by reverse prep-HPLC to get the title compound. Yield: 16% (0.015 g) LCMS m / z = 449[M+H]+;1H-NMR (400 MHz, DMSO-d6): 11.39 (bs, 1H), 8.25 (d, 1H), 7.76-7.73 (m, 1H), 7.63 (s, 1H), 7.43-7.41 (m, 2H), 7.36-7.34 (m, 2H), 5.88 (s, 1H), 3.96 (bs, 1H), 2.98 (s, 3H). Example 201 (3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-1H-imidazol-2-yl)(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methanol Step 1: 3-Chloro-4-fluorophenyl)(4-(methylsulfonyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2- yl)methanone (intermediate 25, mixture of regioisomers, 340 mg, 0.785 mmol) was dissolved in HCl in 1,4-diox- ane (4M, 10 mL) at 0 °C. The resulting reaction mixture was stirred at rt for 5 h. The reaction mixture was con- centrated under reduced pressure, the residue was taken up in water (5 mL) and basified with NaHCO3(5 mL). The precipitated solid was filtered off and dried under vacuum to afford (3-chloro-4-fluorophenyl)(4-(methyl- sulfonyl)-1H-imidazol-2-yl)methanone (200 mg, 84%). Step 2: 5-Bromo-2-(2,2,2-trifluoroethoxy) pyridine (2.537 g, 9.911 mmol) was added in one portion to a stirred solution of a mixture of magnesium turnings (237.856 mg, 9.911 mmol) and iodine (2 mg) in THF (1.4 mL) at room temperature under an argon atmosphere. The temperature rose to about 60 °C after formation of the Grignard reagent. The reaction mixture was allowed to cool to room temperature and was stirred for 1 h. The reaction mixture was cooled to 0 °C and a solution of (3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-1H-imidazol-2- yl)methanone (200 mg, 0.661 mmol) in THF (6.6 mL) was added dropwise. The reaction mixture was stirred at room temperature for 3 h. The reaction mixture was cooled to 0 °C, quenched with NH4Cl Sat. solution (15 mL) and extracted with ethyl acetate (3×30 mL). The combined organic layers were washed with brine (10 mL), dried 114 GRA 4216-foreign filing over anhydrous Na2SO4and concentrated under reduced pressure. The obtained residue was purified by prep- HPLC to afford the title compound (90 mg, 28%). LCMS m / z = 480[M+H]+;1H-NMR (400 MHz, DMSO-d6): 13.00 (s, 1H), 8.12 (dd, 1H), 7.78 (s, 1H), 7.73 (dd, 1H), 7.58 (dd, 1H), 7.42-7.37 (m, 2H), 7.35-7.31 (m, 1H), 6.97 (dd, 1H), 4.98 (q, 2H), 3.10 (s, 3H). Example 202 (2-((3-chloro-4-fluorophenyl)(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methyl)-1H-imidazol-4-yl)(imino)(methyl)- l6-sulfanone Step 1: Sodium hydride (69.471 mg, 1.737 mmol) was added to a solution of 5-((3-chloro-4-fluorophenyl)(4-(me- thylthio)-1H-imidazol-2-yl)methyl)-2-(2,2,2-trifluoroethoxy)pyridine (intermediate 45, 300 mg, 0.695 mmol) in THF (6 mL) at 0 °C under an argon atmosphere. The reaction mixture was stirred at 0 °C for 5 min followed by the addition of SEM-Cl (0.308 mL, 1.737 mmol) at 0 °C and stirring for 15 min. The reaction mixture was diluted with ice water (10 mL) and extracted with ethyl acetate (3×25 mL). The solvent was evaporated under reduced pressure to afford 5-((3-chloro-4-fluorophenyl)(4-(methylthio)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imid- azol-2-yl)methyl)-2-(2,2,2-trifluoroethoxy)pyridine and the corresponding SEM regioisomer (570 mg, crude). Step 2: 5-((3-chloro-4-fluorophenyl)(4-(methylthio)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)me- thyl)-2-(2,2,2-trifluoroethoxy)pyridine (mixture of regioisomers, 570 mg, 1.014 mmol) was dissolved in methanol (10 mL) at room tempereature followed by the addition of phenyl-l3-iodanediyl diacetate (979.882 mg, 3.042 mmol) and ammonium carbonate (478.019 mg, 3.042 mmol) at room temperature. The resulting reaction mixture was stirred at room temperature for 4 h. The reaction mixture was concentrated under reduced pressure, the residue was taken up in with water (10 mL) and extracted with ethyl acetate (3×30 mL). The combined organic layers were washed with brine (10 mL), dried over Na2SO4 and evaporated to afford (2-((3-chloro-4-fluorophenyl)(6- (2,2,2-trifluoroethoxy)pyridin-3-yl)methyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)(imino)(me- thyl)-l6-sulfanone and the corresponding SEM regioisomer (750 mg, crude). Step 3: (2-((3-chloro-4-fluorophenyl)(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methyl)-1-((2-(trimethylsilyl)eth- oxy)methyl)-1H-imidazol-4-yl)(imino)(methyl)-l6-sulfanone (mixture of regioisomers, 0.75 g, 1.265 mmol) was added to HCl in 1,4-dioxane (4N, 30 mL) at 0 °C. The resulting reaction mixture was stirred at room temperature for 4 h. The reaction mixture was concentrated under reduced pressure, basified with NaHCO3solution (pH= 7-8) and extracted with ethyl acetate (3×80 mL). The combined organic layers were dried over anhydrous Na2SO4and concentrated under reduced pressure. The crude product was washed with diethyl ether (10 mL) and purified by prep-HPLC to afford the title compound (mixture of isomers) (80 mg). 115 GRA 4216-foreign filing The title compound (mixture of isomers) was separetad into the individual stereoisomers using two subsequent chiral SFC runs. 202a: LCMS m / z = 463 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.68 (br s, 1H), 8.15 (d, 1H), 7.77 (dd, 1H), 7.63 (s, 1H), 7.52 (dd, 1H), 7.41-7.37 (m, 1H), 7.33-7.29 (m, 1H), 6.97 (d, 1H), 5.69 (s, 1H), 4.96 (q, 2H), 3.95 (br s, 1H), 3.00 (s, 3H).202b: LCMS m / z = 463 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.67 (s, 1H), 8.15 (d, 1H), 7.77 (dd, 1H), 7.64 (s, 1H), 7.52 (dd, 1H), 7.42-7.37 (m, 1H), 7.32-7.29 (m, 1H), 6.97 (d, 1H), 5.69 (s, 1H), 4.96 (q, 2H), 3.95 (br s, 1H), 3.00 (s, 3H). 202c: LCMS m / z = 463 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.67 (s, 1H), 8.15 (d, 1H), 7.78 (dd, 1H), 7.64 (s, 1H), 7.52 (dd, 1H), 7.42-7.37 (m, 1H), 7.32-7.29 (m, 1H), 6.97 (d, 1H), 5.69 (s, 1H), 4.96 (q, 2H), 3.95 (br s, 1H), 3.00 (s, 3H).202d: LCMS m / z = 463 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.68 (s, 1H), 8.15 (d, 1H), 7.77 (dd, 1H), 7.67 (d, 1H), 7.52 (dd, 1H), 7.42-7.37 (m, 1H), 7.33- 7.29 (m, 1H), 6.98 (d, 1H), 5.71 (s, 1H), 4.96 (q, 2H), 4.22 (br s, 1H), 3.02 (s, 3H). Chiral SFC: column: Chiralcel OX-H (4.6 x 250 mm) 5 m; co-solvent: iPrOH, flow: 3 mL / min; % of co-solvent: 25%; ABPR: 1500 psi T: 35 °C; (202a) Rt = 5.82 min (first eluting), (202b) Rt = 6.47 min (second eluting), (202c) Rt = 9.13 min (third eluting), (202d) Rt = 10.48 min (fourth eluting). Example 203 The title compound was prepared from the appropriate intermediates and reagents using an analogous method to that described for example 202. Example Name / Structure / Data 203a, 203b, (2-((3-chloro-4-fluorophenyl)(5-chloro-6-(trifluoromethyl)pyridin-3-yl)methyl)-1H-imida- 203c, 203d zol-4-yl)(imino)(methyl)-l6-sulfanone Without step 1, from intermediate 46. 203a: LCMS m / z = 467 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.73 (s, 1H), 8.72 (d, 1H), 8.23 (s, 1H), 7.70 (s, 1H), 7.61 (dd, 1H), 7.45-7.40 (m, 1H), 7.36 (dd, 1H), 5.92 (s, 1H), 116 GRA 4216-foreign filing 3.98 (s, 1H), 3.02 (s, 3H).203b: LCMS m / z = 467 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.73 (s, 1H), 8.72 (d, 1H), 8.23 (s, 1H), 7.70 (s, 1H), 7.61 (dd, 1H), 7.45-7.40 (m, 1H), 7.36 (dd, 1H), 5.92 (s, 1H), 3.98 (s, 1H), 3.02 (s, 3H).203c: LCMS m / z = 467 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.73 (s, 1H), 8.72 (d, 1H), 8.23 (s, 1H), 7.70 (s, 1H), 7.61 (dd, 1H), 7.45-7.40 (m, 1H), 7.36 (dd, 1H), 5.92 (s, 1H), 3.98 (s, 1H), 3.02 (s, 3H).203d: LCMS m / z = 467 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.73 (s, 1H), 8.72 (d, 1H), 8.23 (s, 1H), 7.70 (s, 1H), 7.61 (dd, 1H), 7.45-7.40 (m, 1H), 7.36 (dd, 1H), 5.92 (s, 1H), 3.98 (s, 1H), 3.02 (s, 3H). Chiral SFC: column: Chiralcel IC (4.6 x 250 mm) 5 m; co-solvent: iPrOH, flow: 3 mL / min; % of co-solvent: 20%; ABPR: 1500 psi; T: 35 °C; (203a) Rt = 5.88 min (first elu- ting), (203b) Rt = 6.91 min (second eluting), (203c) Rt = 9.92 min (third eluting), (203d) Rt = 12.47 min (fourth eluting). Example 204 (3-chloro-4-fluorophenyl)(3,3-difluorocyclopentyl)(4-methyl-5-(methylsulfonyl)-1H-imidazol-2-yl)methanol Step 1: (3-Chloro-4-fluorophenyl)(3,3-difluorocyclopentyl)(5-methyl-4-(methylsulfonyl)-1-((2- (trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)methanol (intermediate 47, mixture of regioisomers, 0.1 g, 0.181 mmol) was added to a stirred solution of HCl in 1,4-dioxane (4N, 3.0 mL) at room temperature and the mixture was stirred for 4 h. The reaction mixture was concentrated under reduced pressure to afford the crude compound, which was purified by prep HPLC to afford the title compound (40 mg, 52%). LCMS m / z = 421 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.47 (s, 1H), 7.71-7.68 (m, 1H), 7.45-7.35 (m, 2H), 6.44-6.42 (m, 1H), 3.31-3.24 (m, 1H), 3.07 (s, 3H), 2.49-2.33 (m, 3H), 2.22-1.90 (m, 4H), 1.81-1.61 (m, 1H), 1.58- 1.50 (m, 1H), 1.32-1.23 (m, 1H). Example 205 5-( 5-(methylsulfonyl)-1H-imidazol-2-yl)methyl)-4-methyloxazol-2-amine Step 1: To a solution of (3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-1-((2-(trimethylsilyl)ethoxy)me- thyl)-1H-imidazol-2-yl)methyl diisopropylcarbamate (intermediate 49, 1 g, 1.736 mmol) in THF (20 mL) was 117 GRA 4216-foreign filing added 4-methyloxazol-2-amine (0.341 g, 3.471 mmol) followed by boron trifluoride etherate (0.369 mL, 2.603 mmol) and trifluoroacetic acid (0.396 mL, 3.471 mmol) at room temperature. Then reaction mixture was heated to 50 °C for 1 h. The reaction mixture was concentrated under reduced pressure to get the crude compound, which upon purification by column chromatography (C18, 0.1% formic acid in water / acetonitrile) followed by prep- HPLC afforded 5 mg (1%) of the title compound. LCMS m / z = 399 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.48 (s, 1H), 7.51 (dd, 1H), 7.41 (t, 1H), 7.33-7.20 (m, 1H), 6.46 (br s, 2H), 5.69 (s, 1H), 3.02 (s, 3H), 2.37 (s, 3H), 1.75 (s, 3H). LCMS Methods Method A: Waters Acquity H Class UPLC attached with Waters SQD 2 mass spectrometer; Ionisation method: Electro spray Capillary (kV) 3.50, Cone (V) 25.00, Source Temperature (°C) 150, Desolvation Temperature (°C) 400, Cone Gas Flow (L / Hr) -50, Desolvation Gas Flow (L / Hr) -750; Mass range:100 to 900 Da; DAD Wavelength range (nm): 200 to 400; Solvent A: 5 mM NH4OAc in water and Solvent B: 5 mM NH4OAc in ACN: Water (90:10); Flow rate: 1.20 ml / min; (mobile phase: 95% [5 mM NH4OAc in water] and 5% [5 mM NH4OAc in ACN: Water (90:10)] held for 0.75 min, then 85% [5 mM NH4OAc in water] and 15% [5 mM NH4OAc in ACN: Water (90:10)] in 1.25 min further 70% [5 mM NH4OAc in water] and 30% [5 mM NH4OAc in ACN: Water (90:10)] in 2.50 min, and finally 2% [5 mM NH4OAc in water] and 98% [5 mM NH4OAc in ACN: Water (90:10)] in 3.75 min, held this mobile phase composition up to 4.25 min and finally back to initial condition in 4.50 min and held this composition up to 5.10 min). TIME Flow Rate (ml / min) %A (5 mM % B (5 mM NH4OAc in NH4OAc in ACN: water) Water (90:10)) 0.00 1.20 95 5 0.75 1.20 95 5 1.25 1.20 85 15 2.50 1.20 70 30 3.75 1.20 2 98 4.25 1.20 2 98 4.50 1.20 95 5 5.10 1.20 95 5 Column Used: Xbridge C18 column (3.5 µm, 50 x 3 mm); Column Temperature: 40°C. Method B Waters Acquity H Class UPLC attached with Waters SQD 2 mass spectrometer; Ionisation method: Electro spray; Capillary (kV) 3.50, Cone (V) 25.00, Source Temperature (°C) 150, Desolvation Temperature (°C) 400, Cone Gas Flow (L / Hr) -50, Desolvation Gas Flow (L / Hr) -750;Mass range:100 to 900 Da; DAD Wavelength range (nm): 118 GRA 4216-foreign filing 200 to 400; Solvent A: 5 mM NH4OAc in water and Solvent B: 5 mM NH4OAc in ACN: Water (90:10); Flow rate: 1.00 ml / min; (mobile phase: from 98% [5 mM NH4OAc in water] and 2% [5 mM NH4OAc in ACN: Water (90:10)] to 85% [5 mM NH4OAc in water] and 15% [5 mM NH4OAc in ACN: Water (90:10)] in 1.00 min, then 60% [5 mM NH4OAc in water] and 40% [5 mM NH4OAc in ACN: Water (90:10)] in 6.50 min, and finally 2% [5 mM NH4OAc in water] and 98% [5 mM NH4OAc in ACN: Water (90:10)] in 8.00 min, held this mobile phase composition up to 10.00 min and finally back to initial condition in 11.00 min and held this composition up to 12.00 min). TIME Flow Rate (ml / min) %A (5 mM % B (5 mM NH4OAc in NH4OAc in ACN: water) Water (90:10) ) 0.00 1.00 98 2 1.00 1.00 85 156.50 1.00 60 408.00 1.00 2 9810.00 1.00 2 9811.00 1.00 98 212.00 1.00 98 2Column Used: Xbridge C18 column (3.5 µm, 50 x 3 mm); Column Temperature: 40°C. Method B (K91-5-min) Waters Acquity H Class UPLC attached with Waters SQD 2 mass spectrometer; Ionisation method: Electro spray; Capillary (kV) 3.50, Cone (V) 25.00, Source Temperature (°C) 150, Desolvation Temperature (°C) 400, Cone Gas Flow (L / Hr) -50, Desolvation Gas Flow (L / Hr) -750; Mass range:100 to 900 Da; DAD Wavelength range (nm): 200 to 400; Solvent A: 5 mM NH4OAc in water and Solvent B: 5 mM NH4OAc in ACN: Water (90:10); Flow rate: 1.20 ml / min; (mobile phase: 95% [5 mM NH4OAc in water] and 5% [5 mM NH4OAc in ACN: Water (90:10)] held for 0.75 min, then 85% [5 mM NH4OAc in water] and 15% [5 mM NH4OAc in ACN: Water (90:10)] in 1.25 min further 70% [5 mM NH4OAc in water] and 30% [5 mM NH4OAc in ACN: Water (90:10)] in 2.50 min, and finally 2% [5 mM NH4OAc in water] and 98% [5 mM NH4OAc in ACN: Water (90:10)] in 3.75 min, held this mobile phase composition up to 4.25 min and finally back to initial condition in 4.50 min and held this composition up to 5.10 min). TIME Flow Rate (ml / min) %A (5 mM % B (5 mM NH4OAc in NH4OAc in ACN: water) Water (90:10) 0.00 1.20 95 5 0.75 1.20 95 5 1.25 1.20 85 15 2.50 1.20 70 30 3.75 1.20 2 98 119 GRA 4216-foreign filing 4.25 1.20 2 98 4.50 1.20 95 5 5.10 1.20 95 5 Column Used: Xbridge C18 column (3.5 µm, 50 x 3 mm); Column Temperature: 40°C. Method C (K91-12-min) Waters Acquity H Class UPLC attached with Waters SQD 2 mass spectrometer; Ionisation method: Electro spray; Capillary (kV) 3.50, Cone (V) 25.00, Source Temperature (°C) 150, Desolvation Temperature (°C) 400, Cone Gas Flow (L / Hr) -50, Desolvation Gas Flow (L / Hr) -750; Mass range:100 to 900 Da; DAD Wavelength range (nm): 200 to 400; Solvent A: 5 mM NH4OAc in water and Solvent B: 5 mM NH4OAc in ACN: Water (90:10); Flow rate: 1.00 ml / min; (mobile phase: from 98% [5 mM NH4OAc in water] and 2% [5 mM NH4OAc in ACN: Water (90:10)] to 85% [5 mM NH4OAc in water] and 15% [5 mM NH4OAc in ACN: Water (90:10)] in 1.00 min, then 60% [5 mM NH4OAc in water] and 40% [5 mM NH4OAc in ACN: Water (90:10)] in 6.50 min, and finally 2% [5 mM NH4OAc in water] and 98% [5 mM NH4OAc in ACN: Water (90:10)] in 8.00 min, held this mobile phase composition up to 10.00 min and finally back to initial condition in 11.00 min and held this composition up to 12.00 min). TIME Flow Rate (ml / min) %A (5 mM % B (5 mM NH4OAc in NH4OAc in ACN: water) Water (90:10) 0.00 1.00 98 2 1.00 1.00 85 156.50 1.00 60 408.00 1.00 2 9810.00 1.00 2 9811.00 1.00 98 212.00 1.00 98 2Column Used: Xbridge C18 column (3.5 µm, 50 x 3 mm); Column Temperature: 40°C. The following prophetic examples could be synthesized according to the general schemes and by analogy to the synthetic procedures described above: Prophetic ex- Structure ample num- Chemical name ber GRA 4216-foreign filing 2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-N-cyclopro- pyl-1H-imidazole-4-sulfonamide 2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-4-(pyrroli- din-1-ylsulfonyl)-1H-imidazole 2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-4-((3,3- difluoropyrrolidin-1-yl)sulfonyl)-1H- imidazole 4-((2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-1H-imid- azol-4-yl)sulfonyl)piperazin-2-one 2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-N,N-dime- thyl-1H-imidazole-4-sulfonamide GRA 4216-foreign filing -((2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-1H-imid- azol-4-yl)sulfonyl)-4-methylpipera- zine 2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-N-(tetrahy- drofuran-3-yl)-1H-imidazole-4-sul- fonamide 2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-N-(3-hy- droxycyclopentyl)-1H-imidazole-4- sulfonamide -((2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-1H-imidaz- ole)-4-sulfonamido)acetamide GRA 4216-foreign filing 2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-4-((3-meth- oxy-3-methylpyrrolidin-1-yl)sul- fonyl)-1H-imidazole 2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-N-(2-meth- oxypropyl)-1H-imidazole-4-sulfona- mide 4-(azetidin-3-ylsulfonyl)-2-((3- chloro-4-fluorophenyl)(3,4-difluoro- phenyl)methyl)-1H-imidazole -((2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-1H-imidaz- ole)-4-sulfonamido)propanamide 2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-4-((1- methylazetidin-3-yl)sulfonyl)-1H- imidazole GRA 4216-foreign filing ((2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-1H-imid- azol-4-yl)sulfonyl)glycine 2-((2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-N-methyl- 1H-imidazole)-4-sulfonamido)acet- amide 2-((2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-1H-imid- azol-4-yl)sulfonyl)-2,5-diazabicy- clo[2.2.1]heptane 1-((2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-1H-imid- azol-4-yl)sulfonyl)piperidin-3-amine (1-((2-((3-chloro-4-fluoro- phenyl)(3,4-difluorophenyl)methyl)- 1H-imidazol-4-yl)sulfonyl)azetidin- 3-yl)methanamine GRA 4216-foreign filing -((2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-1H-imid- azol-4-yl)sulfonyl)piperidine 2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-4-(pyrroli- din-3-ylsulfonyl)-1H-imidazole -((2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-1H-imid- azol-4-yl)sulfonyl)-1-methylpiperi- dine 2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-4-((1- methylpyrrolidin-3-yl)sulfonyl)-1H- imidazole 2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-N-(pyrroli- din-3-yl)-1H-imidazole-4-sulfona- mide 125 GRA 4216-foreign filing N-(azetidin-3-yl)-2-((3-chloro-4- fluorophenyl)(3,4-difluoro- 121 phenyl)methyl)-1H-imidazole-4-sul- fonamide O O S NH F NH N N-(azetidin-3-ylmethyl)-2-((3- F N chloro-4-fluorophenyl)(3,4-difluoro- H 122 phenyl)methyl)-1H-imidazole-4-sul- fonamide Cl F 2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-N-(2-hy- 123 droxycyclopentyl)-1H-imidazole-4- sulfonamide 1-((2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-1H-imid- 124 azol-4-yl)sulfonyl)-3,5-dimethylpi- perazine 2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-N-(pyrroli- 125 din-3-ylmethyl)-1H-imidazole-4-sul- fonamide GRA 4216-foreign filing 2-((3-chloro-4-fluorophenyl)(3,4- difluorophenyl)methyl)-N-(2-(dime- thylamino)ethyl)-5-methyl-1H-imid- azole-4-sulfonamide N-(3-aminocyclobutyl)-2-((3-chloro- 4-fluorophenyl)(3,4-difluoro- phenyl)methyl)-1H-imidazole-4-sul- fonamide 2-(((2-(bis(3-chloro-4-fluoro- phenyl)methyl)-1H-imidazol-4- yl)(methyl)(oxo)-l6-sulfaneyli- dene)amino)acetamide 2-amino-N-((2-(bis(3-chloro-4-fluor- ophenyl)methyl)-1H-imidazol-4- yl)(methyl)(oxo)-l6-sulfaneyli- dene)acetamide (2-(bis(3-chloro-4-fluorophenyl)me- thyl)-1H-imidazol-5-yl)(imino)(1- methylazetidin-3-yl)-l6-sulfanone 127 GRA 4216-foreign filing 2-((3-chloro-4-fluorophenyl)(3,3-di- 136 methylcyclobutyl)methyl)-5-methyl- 4-(methylsulfonyl)-1H-imidazole 2-((3-chloro-4-fluorophenyl)(6,6- difluorospiro[3.3]heptan-2-yl)me- 137 thyl)-5-methyl-4-(methylsulfonyl)- 1H-imidazole 2-((3-chloro-4-fluorophenyl)(3- (difluoromethoxy)cyclobutyl)me- 138 thyl)-5-methyl-4-(methylsulfonyl)- 1H-imidazole 2-((3-chloro-4-fluoro- phenyl)(spiro[2.3]hexan-5-yl)me- 139 thyl)-5-methyl-4-(methylsulfonyl)- 1H-imidazole (2-(bis(3-(trifluoromethoxy)phe- 146 nyl)methyl)-5-methyl-1H-imidazol- 4-yl)(imino)(methyl)-l6-sulfanone Electrophysiology: Voltage-Clamp recordings The following NaV1.8 recombinant cell line was used for recordings: HEK-NaV1.8 (NM_006514.1) with b3 (NM_018400.3). Sodium currents were measured using the patch clamp technique in the whole-cell configuration using the Qube384 (Sophion A / S, Copenhagen, Denmark) automated voltage clamp platform. ^Multi hole^ plates were used 128 GRA 4216-foreign filing for the cell line expressing NaV1.8 while ^single or multi hole^ plates were used for the recombinant cell lines expressing the other subtypes. Appropriate filters (for minimum seal resistance and minimum current size) and series resistance compensation (for high quality sodium channel recordings) were applied. Data was collected at ambient room temperature or 19 °C. The recording extracellular solution contained (in mM): NaCl 145 mM, KCl 4 mM, CaCl22 mM, MgCl21 mM, HEPES 10 mM, Glucose 10 mM, pH 7.4 (NaOH). The intracellular recording solution contained (in mM): CsF 120 mM, CsCl 20 mM, NaCl 10 mM, EGTA 10 mM, HEPES 10 mM, pH 7.2 (CsOH). Currents were recorded at 25 kHz sampling frequency and filtered at 5 kHz. Series resistance compensation was applied at 65%. Vehicle (VEH) is the control condition where cells are exposed to 0.3% DMSO without compound. All runs in- clude VEH controls being exposed to the same voltage protocols to assess non-compound related phenomena such as run down and then used to isolate compound dependent effects on currents. To check for state-dependent inhibition, the following voltage-sequence was applied every 20 seconds: From a resting membrane potential of -120 mV, the first test pulse (P1; 20 ms to -10 mV) was applied to check for channels in the Resting State followed by a brief recovery (100 ms to -120 mV), then holding the membrane voltage to V1 / 2 (4 seconds at voltage to obtain half the channel at Rest and half Inactivated) with a subsequent second test pulse (P2; 20 ms to -10 mV) to check for channels in the Inactivated State, followed by another brief recovery (20 ms to -120 mV) and a final third test pulse (P3; 20 ms to -10 mV) to check for recovered channels. To check for frequency-dependent inhibition, a 10 Hz protocol and a 20 Hz protocol were applied; namely, From a resting membrane potential of -120 mV, 40-pulses (10 ms to -10 mV) was applied at 10 Hz (at 100 ms between pulses) and then at 20 Hz (at 50 ms between pulses). Each parameter was recorded (P1, P2, P3, P40 from 10Hz and P40 from 20Hz) during a control period (lasting ~ 5 minutes) when establishing the baseline and during compound period (lasting ~ 12 minutes) when test compound (or vehicle) was applied. For each parameter, the value at the end of the compound period was normalized to the vehicle baseline; as follows To adjust for any variance in the Na+current signal during the compound period (owing to cumulative inactivation independent of compound or shifts in biophysics over time), a dedicated segment of the recording wells in each 384 plate were dedicated to having only vehicle exposure. These vehicle-only recordings were used to correct for any apparent ^run-up^ or ^run-down^ in the The adjusted inhibition was 100Percent inhibition was determined and IC50values were calculated using a 4 parameter logistic model within XLFit Software (IDBS, Boston MA): 129 GRA 4216-foreign filing % where A and B are the maximal the IC50concentration and D is the (Hill) slope. The potency data of the example compounds are summarized in the table below (category A: human NaV1.8 IC500.1 M; category B: 0.1 M < human NaV1.8 IC501 M; category C: 1 M < human NaV1.8 IC5010 M; ^n.d.^: not determined): Example Potency category Example Potency category Example Potency category1 A 80 A 175b C 2 A 81 B 176 n.d. 3 A 82a A 177 A 4 A 82b A 178a B 5 A 87 A 178b A 6 B 88a A 179 A 7 A 88b B 180a B 8 B 89 B 180b A 9 A 91 A 181 A 10 A 92a A 182 A 11 A 92b B 183 A 12 A 93 A 184a A 13 B 130a A 184b A 14 A 130b A 185a A 15 B 131 B 185b A 16 A 132a A 186a A 17 A 132b B 186b A 18 A 132c A 187a A 19 B 132d B 187b A 20 A 133a A 188a A 21 A 133b A 188b A 22 B 135a B 189a A 23 A 135b A 189b A 24 A 140a A 190a A 25 A 140b A 190b A 26 B 141a A 191 A 27 A 141b A 192a B 28 A 142a A 192b B 29 B 142b A 193 A 30 B 143a A 194 A 31 A 143b A 195 A 32 A 144a A 196 A 33 A 144b A 197 A 34 B 145a A 198 A 35 A 145b A 199 A 36 A 148 A 200 A 37 B 149a A 201 C 38 A 150 A 202a B 39 B 151 A 202b A 40 A 152 A 202c B 41 A 153 B 202d B 43 A 154a A 203a B 44 B 155a A 203b B 45 A 156 A 203c B 46 B 157a A 203d B 47 A 158a A 204 B 130 GRA 4216-foreign filing n.d. 158b A 205 C n.d. 159 A n.d. 160a A n.d. 161a A n.d. 161b A n.d. 162 B n.d. 163a A A 164 A A 165 A A 166 A A 167 A n.d. 168 A a A 169 B b A 170 A a A 171 n.d. b A 172 A a A 173 B b A 174 C A 175a C

Claims

131 GRA 4216-foreign filing CLAIMS 1. A compound according to general formula (I)wherein R1 represents H or OH; A and B independently from one another represent phenyl, 5 to 10-membered heteroaryl, C3-7-cycloalkyl, or 4- to 10-membered heterocycloalkyl; R2and R3independently from one another represent F, Cl, CN, C1-4-alkyl, C3-6-cycloalkyl, NH2, N(H)C1-4-alkyl, N(C1-4-alkyl)2, OH, or O-C1-4-alkyl; x and y independently from one another represent 0, 1, 2, 3, or 4; R4represents H, Cl, C1-6-alkyl, or C3-6-cycloalkyl; L represents bond, C1-3-alkylene or C1-2-alkylene-N(H); and R5represents S(=O)R6, S(=O)(=NH)R6, S(=O)(=N(C1-4-alkyl))R6, S(=O)(=NR6)R6, S(=O)2R6, S(=O)2NH2, S(=O)2N(H)R6, or S(=O)2N(C1-4-alkyl)R6; R6 represents C1-6-alkyl, C3-7-cycloalkyl, 4- to 10-membered heterocycloalkyl, C1-4-alkylene-(C3-7-cy- cloalkyl), or C1-4-alkylene-(4- to 7-membered heterocycloalkyl); or R4and R5together with the carbon atoms to which they are connected form 5- to 7- membered hetero- cycloalkyl; wherein C1-6-alkyl, C1-4-alkyl, C1-4-alkylene, C1-3-alkylene and C1-2-alkylene in each case independently from one another is linear or branched, saturated or unsaturated; wherein C1-6-alkyl, C1-4-alkyl, C1-4-alkylene, C1-3-alkylene, C1-2-alkylene, C3-6-cycloalkyl, C5-7-cycloalkyl, 4- to 7- membered heterocycloalkyl, 4- to 10- membered heterocycloalkyl, and 5- to 7- membered hetero- cycloalkyl in each case independently from one another are unsubstituted or mono- or polysubstituted with one or more substituents selected from F; Cl; CN; C1-6-alkyl; C1-6-alkylene-NH2, CF3; CF2H; CFH2; C(O)- C1-6-alkyl; C(O)-OH; C(O)-OC1-6-alkyl; C(O)-NH2; C(O)-N(H)(C1-6-alkyl); C(O)-N(C1-6-alkyl)2; OH; =O; OCF3; OCF2H; OCFH2; O-C1-6-alkyl; NH2; N(H)(C1-6-alkyl); N(C1-6-alkyl)2; N(H)-C(O)-C1-6-alkyl; and S(O)2-C1-6-alkyl; wherein phenyl, 5 to 10-membered heteroaryl and 5 or 6-membered heteroaryl in each case independently from one another are unsubstituted or mono- or polysubstituted with one or more substituents selected from132 GRA 4216-foreign filing F; Cl; CN; C1-6-alkyl; CF3; CF2H; CFH2; OH; OCF3; OCF2H; OCFH2; O-C1-6-alkyl; NH2; N(H)(C1-6-alkyl); and N(C1-6-alkyl)2; in the form of the free compound or a physiologically acceptable salt thereof.

2. The compound according to claim 1, wherein R1 represents H.

3. The compound according to claim 1 or 2, wherein x and y independently from one another represent 1 or 2.

4. The compound according to any of the preceding claims, wherein at least one of A and B represents phenyl or 5- or 6-membered heteroaryl.

5. The compound according to any of the preceding claims, wherein A represents phenyl.

6. The compound according to any of the preceding claims, wherein B represents phenyl, 5- or 6-membered heteroaryl, or C3-7-cycloalkyl.

7. The compound according to any of the preceding claims, wherein R2represents F, Cl, OCH3, OCF3, or CHF2.

8. The compound according to any of the preceding claims, wherein R3 represents F, Cl, NH2, CH3, CF3, CHF2, OCH3, OCF3, OCHF2 or O-CH2-CF3.

9. The compound according to any of the preceding claims, wherein L represents bond or C1-3-alkylene.

10. The compound according to any of the preceding claims, wherein R5represents S(=O)R6, S(=O)(=NH)R6, S(=O)(=N(C1-4-alkyl))R6, S(=O)2R6, S(=O)2NH2, S(=O)2N(H)R6, or S(=O)2N(C1-4-alkyl)R6.

11. The compound according to any of the preceding claims, wherein R6represents (vi) C1-6-alkyl selected from the group consisting of methyl, ethyl, n-propyl, 2-propyl, n-butyl, isobu- tyl, sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 3-pentyl, 2-methylbutyl, 3-methylbutyl, 3-methylbut- 2-yl, 2-methylbut-2-yl, 2,2-dimethylpropyl, and n-hexyl; (vii) C3-7-cycloalkyl selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclo- hexyl, cycloheptyl, spiro[2.2]pentyl, spiro[2.3]hexyl, spiro[3.3]heptyl, bicyclo[1.1.0]butyl, bicy- clo[2.1.0]pentyl, bicyclo[2.1.1]hexyl, bicyclo[3.1.1]heptyl, bicyclo[2.2.1]heptyl, bicy- clo[3.1.0]hexyl, bicyclo[3.2.0]heptyl, and bicyclo[4.1.0]heptyl;133 GRA 4216-foreign filing (viii) 4- to 10-membered heterocycloalkyl selected from the group consisting of 1,1-dioxo tetrahydrothi- ophenyl, 1-oxo thiomorpholinyl, tetrahydropyranyl, oxetanyl, tetrahydrofuranyl, morpholinyl, pyrrolidinyl, pyrrolidinonyl, azetidinyl, piperazinyl, piperazinonyl, piperidinyl, thietanyl, 1,1-di- oxothietanyl, 2,6-diazaspiro[3.3]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, tetrahydro-2H-thiopyranyl 1,1-dioxide, azepanyl, dioxepanyl, oxazepanyl, diazepanyl, thiazolidinyl, tetrahydrothiophenyl, tetrahydropyridinyl, thiomorpholinyl, 4-methylpiperazinyl, morpholinonyl, dithiolanyl, dihydro- pyrrolyl, dioxanyl, dioxolanyl, dihydropyridinyl, dihydrofuranyl, dihydroisoxazolyl, dihydrooxa- zolyl, imidazolidinyl, isoxazolidinyl, oxazolidinyl, and pyrazolidinyl; (ix) C1-4-alkylene-(C3-7-cycloalkyl) selected from the group consisting of (CH2)1-2-cyclopropyl, (CH2)1-2-cyclobutyl, (CH2)1-2-cyclopentyl, (CH2)1-2-cyclohexyl; (CH2)1-2-cycloheptyl, (CH2)1-2- spiro[2.2]pentyl, (CH2)1-2-spiro[2.3]hexyl, (CH2)1-2-spiro[3.3]heptyl, (CH2)1-2-bicyclo[1.1.0]bu- tyl, (CH2)1-2-bicyclo[2.1.0]pentyl, (CH2)1-2-bicyclo[2.1.1]hexyl, (CH2)1-2-bicyclo[3.1.1]heptyl, (CH2)1-2-bicyclo[2.2.1]heptyl, (CH2)1-2-bicyclo[3.1.0]hexyl, (CH2)1-2-bicyclo[3.2.0]heptyl, and (CH2)1-2-bicyclo[4.1.0]heptyl; or (x) C1-4-alkylene-(4- to 7-membered heterocycloalkyl) selected from the group consisting of (CH2)1- 2-(1,1-dioxo tetrahydrothiophenyl), (CH2)1-2-(1-oxo thiomorpholinyl), (CH2)1-2-tetrahydropyranyl, (CH2)1-2-oxetanyl, (CH2)1-2-tetrahydrofuranyl, (CH2)1-2-morpholinyl, (CH2)1-2-pyrrolidinyl, (CH2)1-2-pyrrolidinonyl, (CH2)1-2-azetidinyl, (CH2)1-2-piperazinyl, (CH2)1-2-piperazinonyl, (CH2)1-2-piperidinyl, (CH2)1-2-thietanyl, (CH2)1-2-(1,1-dioxothietanyl), (CH2)1-2-(2,6-diazaspiro[3.3]hep- tyl), (CH2)1-2-(2,5-diazabicyclo[2.2.1]heptyl), (CH2)1-2-tetrahydro-2H-thiopyranyl 1,1-dioxide, (CH2)1-2-azepanyl, (CH2)1-2-dioxepanyl, (CH2)1-2-oxazepanyl, (CH2)1-2-diazepanyl, (CH2)1-2-thia- zolidinyl, (CH2)1-2-tetrahydrothiophenyl, (CH2)1-2-tetrahydropyridinyl, (CH2)1-2-thiomorpholinyl, (CH2)1-2-(4-methylpiperazinyl), (CH2)1-2-morpholinonyl, (CH2)1-2-dithiolanyl, (CH2)1-2-dihydro- pyrrolyl, (CH2)1-2-dioxanyl, (CH2)1-2-dioxolanyl, (CH2)1-2-dihydropyridinyl, (CH2)1-2-dihydro- furanyl, (CH2)1-2-dihydroisoxazolyl, (CH2)1-2-dihydrooxazolyl, (CH2)1-2-imidazolidinyl, (CH2)1-2- isoxazolidinyl, (CH2)1-2-oxazolidinyl, and (CH2)1-2-pyrazolidin; wherein said methyl, ethyl, n-propyl, 2-propyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 3-pentyl, 2-methylbutyl, 3-methylbutyl, 3-methylbut-2-yl, 2-methylbut-2-yl, 2,2-dimethylpropyl, n-hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, spiro[2.2]pentyl, spiro[2.3]hexyl, spiro[3.3]heptyl, bicyclo[1.1.0]butyl, bicyclo[2.1.0]pentyl, bicyclo[2.1.1]hexyl, bicyclo[3.1.1]heptyl, bicy- clo[2.2.1]heptyl, bicyclo[3.1.0]hexyl, bicyclo[3.2.0]heptyl, and bicyclo[4.1.0]heptyl, 1,1-dioxo tetrahy- drothiophenyl, 1-oxo thiomorpholinyl, tetrahydropyranyl, oxetanyl, tetrahydrofuranyl, morpholinyl, pyr- rolidinyl, pyrrolidinonyl, azetidinyl, piperazinyl, piperazinonyl, piperidinyl, thietanyl, 1,1-dioxothietanyl, 2,6-diazaspiro[3.3]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, tetrahydro-2H-thiopyranyl 1,1-dioxide, azepanyl, dioxepanyl, oxazepanyl, diazepanyl, thiazolidinyl, tetrahydrothiophenyl, tetrahydropyridinyl, thiomor- pholinyl, 4-methylpiperazinyl, morpholinonyl, dithiolanyl, dihydropyrrolyl, dioxanyl, dioxolanyl, dihydro- pyridinyl, dihydrofuranyl, dihydroisoxazolyl, dihydrooxazolyl, imidazolidinyl, isoxazolidinyl, oxazoli- dinyl, and pyrazolidinyl in each case independently from one another are unsubstituted or mono- or pol- ysubstituted with one or more substituents selected from F; Cl; CN; C1-6-alkyl; CF3; CF2H; CFH2; C(O)- C1-6-alkyl; C(O)-OH; C(O)-OC1-6-alkyl; C(O)-NH2; C(O)-N(H)(C1-6-alkyl); C(O)-N(C1-6-alkyl)2; OH; =O;134 GRA 4216-foreign filing OCF3; OCF2H; OCFH2; O-C1-6-alkyl;; NH2; N(H)(C1-6-alkyl); N(C1-6-alkyl)2; N(H)-C(O)-C1-6-alkyl; and S(O)2-C1-6-alkyl.

12. The compound according to any of claims 1 to 9, wherein R4and R5together with the carbon atoms to which they are connected form thiepanyl 1,1-dioxide, 1,2- thiazepanyl 1,1-dioxide, 2,5,6,7-tetrahydro-1,2-thiazepinyl 1,1-dioxide, or 5,6-dihydro-2H-1,2-thiazinyl 1,1-dioxide.

13. The compound according to any of the preceding claims selected from the group consisting of 1 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(methylsulfonyl)-1H-imidazole 2 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(ethylsulfonyl)-1H-imidazole 3 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(cyclopropylsulfonyl)-1H-imidazole 4 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-(isopropylsulfonyl)-1H-imidazole 5 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-((tetrahydrofuran-3-yl)sulfonyl)-1H-imidazole 6 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-((tetrahydro-2H-pyran-4-yl)sulfonyl)-1H-imidazole 7 2-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-4-yl)sulfonyl)ethan-1-amine 8 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-chloro-4-(methylsulfonyl)-1H-imidazole 9 2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole-5-sulfonamide 10 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-methyl-1H-imidazole-5-sulfonamide 11 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(1-(dimethylamino)propan-2-yl)-1H-imidazole-5- sulfonamide 12 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2-(pyrrolidin-1-yl)ethyl)-1H-imidazole-5-sulfona- mide 13 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-4-isopropylpiperazine 14 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-4-ethylpiperazine 15 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-4-(methylsul- fonyl)piperazine 16 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2-hydroxyethyl)-N-methyl-1H-imidazole-5-sulfo- namide 17 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2-methoxyethyl)-1H-imidazole-5-sulfonamide 18 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2-(dimethylamino)ethyl)-1H-imidazole-5-sulfona- mide 19 1-(4-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)piperazin-1- yl)ethan-1-one 20 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2-hydroxypropyl)-1H-imidazole-5-sulfonamide 21 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(oxetan-2-ylmethyl)-1H-imidazole-5-sulfonamide 22 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-N,N-dimethylazeti- din-3-amine 23 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-N,N-dimethylpyrroli- din-3-amine135 GRA 4216-foreign filing 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2-(methylsulfonyl)ethyl)-1H-imidazole-5-sulfona- mide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2-hydroxyethyl)-1H-imidazole-5-sulfonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2-hydroxy-2-methylpropyl)-1H-imidazole-5-sul- fonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(1-methoxypropan-2-yl)-1H-imidazole-5-sulfona- mide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-methyl-N-(2-(methylsulfonyl)ethyl)-1H-imidazole- 5-sulfonamide 4-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)thiomorpholine 1- oxide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(3-methoxypropyl)-1H-imidazole-5-sulfonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(oxetan-3-ylmethyl)-1H-imidazole-5-sulfonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(3-(dimethylamino)propyl)-1H-imidazole-5-sulfo- namide 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-N,N-dimethylpiperi- din-4-amine ethyl ((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)glycinate 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(1,1-dioxidothietan-3-yl)-1H-imidazole-5-sulfona- mide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-((3R,4R)-4-hydroxytetrahydro-2H-pyran-3-yl)-1H- imidazole-5-sulfonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-N-methyl- 1H-imidazole-5-sulfonamide 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)azetidin-3-ol 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2,3-dimethoxypropyl)-1H-imidazole-5-sulfona- mide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(oxetan-3-yl)-1H-imidazole-5-sulfonamide 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)piperazine N-(2-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole)-5-sulfonamido)ethyl)acetamide N-(1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)azetidin-3-yl)aceta- mide 2-((2-(bis(3-chloro-4-fluorophenyl)methyl)-N-methyl-1H-imidazole)-5-sulfonamido)-N-me- thylacetamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(3-methoxycyclobutyl)-1H-imidazole-5-sulfona- mide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(3-hydroxycyclopentyl)-1H-imidazole-5-sulfona- mide N-(1-acetylpiperidin-4-yl)-2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole-5-sulfona- mide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2,2-difluoroethyl)-1H-imidazole-5-sulfonamide136 GRA 4216-foreign filing 3-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole)-5-sulfonamido)-2,2-dimethylpro- panamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(1-methylpiperidin-4-yl)-1H-imidazole-5-sulfona- mide methyl ((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)glycinate 2-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole)-5-sulfonamido)propanamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(cyanomethyl)-1H-imidazole-5-sulfonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-methyl-N-(2-(methylamino)ethyl)-1H-imidazole-5- sulfonamide 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-3-methylpiperazine 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-N-methylpyrrolidin- 3-amine 2-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-2,6-dia- zaspiro[3.3]heptane 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(piperidin-3-yl)-1H-imidazole-5-sulfonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(methylsulfinyl)-1H-imidazole 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-methyl-5-(methylsulfinyl)-1H-imidazole (2-(bis(3-chloro-4-fluorophenyl)methyl)-4-methyl-1H-imidazol-5-yl)(imino)(methyl)-l6-sul- fanone 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-methyl-5-(methylsulfonyl)-1H-imidazole 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-cyclopropyl-5-(methylsulfonyl)-1H-imidazole 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(methylsulfonyl)-4-(trifluoromethyl)-1H-imidazole (2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)(imino)(methyl)-l6-sulfanone (2-(bis(3-chloro-4-fluorophenyl)methyl)-4-(methylsulfonyl)-1H-imidazol-5-yl)methanol 5-((3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-1H-imidazol-2-yl)methyl)-2-(2,2,2-trifluoro- ethoxy)pyridine 2-((3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-1H-imidazol-2-yl)methyl)-4-fluoroaniline 2-(bis(3-chloro-4-fluorophenyl)methyl)-4-((methylsulfonyl)methyl)-1H-imidazole 2-((3-chloro-4-fluorophenyl)(4-(trifluoromethyl)cyclohexyl)methyl)-4-(methylsulfonyl)-1H- imidazole 3-chloro-6-((4-chlorophenyl)(4-(methylsulfonyl)-1H-imidazol-2-yl)methyl)-2-(trifluorome- thyl)pyridine 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-N-cyclopropyl-1H-imidazole-4-sul- fonamide 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-4-(pyrrolidin-1-ylsulfonyl)-1H- imidazole 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-4-((3,3-difluoropyrrolidin-1-yl)sul- fonyl)-1H-imidazole 4-((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazol-4-yl)sul- fonyl)piperazin-2-one137 GRA 4216-foreign filing 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-N,N-dimethyl-1H-imidazole-4-sul- fonamide 1-((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazol-4-yl)sulfonyl)-4- methylpiperazine 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-N-(tetrahydrofuran-3-yl)-1H-imida- zole-4-sulfonamide 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-N-(3-hydroxycyclopentyl)-1H- imidazole-4-sulfonamide 2-((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazole)-4-sulfona- mido)acetamide 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-4-((3-methoxy-3-methylpyrrolidin- 1-yl)sulfonyl)-1H-imidazole 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-N-(2-methoxypropyl)-1H-imida- zole-4-sulfonamide 4-(azetidin-3-ylsulfonyl)-2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imida- zole 2-((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazole)-4-sulfona- mido)propanamide 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-4-((1-methylazetidin-3-yl)sulfonyl)- 1H-imidazole ((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazol-4-yl)sulfonyl)glycine 2-((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-N-methyl-1H-imidazole)-4-sul- fonamido)acetamide 2-((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazol-4-yl)sulfonyl)-2,5- diazabicyclo[2.2.1]heptane 1-((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazol-4-yl)sulfonyl)pipe- ridin-3-amine (1-((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazol-4-yl)sulfonyl)aze- tidin-3-yl)methanamine 4-((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazol-4-yl)sulfonyl)pipe- ridine 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-4-(pyrrolidin-3-ylsulfonyl)-1H- imidazole 4-((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazol-4-yl)sulfonyl)-1- methylpiperidine 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-4-((1-methylpyrrolidin-3-yl)sul- fonyl)-1H-imidazole 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-N-(pyrrolidin-3-yl)-1H-imidazole-4- sulfonamide N-(azetidin-3-yl)-2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazole-4- sulfonamide138 GRA 4216-foreign filing N-(azetidin-3-ylmethyl)-2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imida- zole-4-sulfonamide 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-N-(2-hydroxycyclopentyl)-1H- imidazole-4-sulfonamide 1-((2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imidazol-4-yl)sulfonyl)-3,5- dimethylpiperazine 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-N-(pyrrolidin-3-ylmethyl)-1H- imidazole-4-sulfonamide 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-N-(2-(dimethylamino)ethyl)-5-me- thyl-1H-imidazole-4-sulfonamide N-(3-aminocyclobutyl)-2-((3-chloro-4-fluorophenyl)(3,4-difluorophenyl)methyl)-1H-imida- zole-4-sulfonamide 2-(((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-4-yl)(methyl)(oxo)-l6-sulfaneyli- dene)amino)acetamide 2-amino-N-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-4-yl)(methyl)(oxo)-l6-sul- faneylidene)acetamide 2-((3-chloro-4-fluorophenyl)(5-chlorothiophen-2-yl)methyl)-5-methyl-4-(methylsulfonyl)-1H- imidazole 2-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-1H-imidazol-2-yl)methyl)-5-(trif- luoromethyl)thiazole 2-((3-chloro-4-fluorophenyl)(3,3-difluorocyclopentyl)methyl)-5-methyl-4-(methylsulfonyl)- 1H-imidazole azetidin-3-yl(2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)(imino)-l6-sulfanone (2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)(imino)(1-methylazetidin-3-yl)-l6- sulfanone 2-((4-chloro-3-fluorophenyl)(chroman-3-yl)methyl)-4-methyl-5-(methylsulfonyl)-1H-imida- zole 2-((3-chloro-4-fluorophenyl)(3,3-dimethylcyclobutyl)methyl)-5-methyl-4-(methylsulfonyl)- 1H-imidazole 2-((3-chloro-4-fluorophenyl)(6,6-difluorospiro[3.3]heptan-2-yl)methyl)-5-methyl-4-(methyl- sulfonyl)-1H-imidazole 2-((3-chloro-4-fluorophenyl)(3-(difluoromethoxy)cyclobutyl)methyl)-5-methyl-4-(methylsul- fonyl)-1H-imidazole 2-((3-chloro-4-fluorophenyl)(spiro[2.3]hexan-5-yl)methyl)-5-methyl-4-(methylsulfonyl)-1H- imidazole (2-(bis(3-chloro-2,4-difluorophenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6- sulfanone (2-(bis(3-chloro-4,5-difluorophenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6- sulfanone (2-(bis(5-chloro-2,4-difluorophenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6- sulfanone139 GRA 4216-foreign filing (2-(bis(4-chloro-2-fluorophenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6-sul- fanone (2-(bis(2-chloro-4-fluorophenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6-sul- fanone (2-(bis(4-(trifluoromethoxy)phenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6- sulfanone (2-(bis(3-(trifluoromethoxy)phenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6- sulfanone (2-(bis(3-fluoro-4-(trifluoromethoxy)phenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(me- thyl)-l6-sulfanone 2-((2-(bis(3-chloro-4-fluorophenyl)methyl)-N-methyl-1H-imidazole)-5-sulfonamido)aceta- mide 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-3-methylpiperazine 2-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-2,5-dia- zabicyclo[2.2.1]heptane 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)piperidin-3-amine (1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)azetidin-3-yl)metha- namine ((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)glycine 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(4-hydroxytetrahydrofuran-3-yl)-1H-imidazole-5- sulfonamide 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-3,5-dimethylpipera- zine N-(azetidin-3-ylmethyl)-2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole-5-sulfonamide 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-2-methylpiperazine 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(pyrrolidin-3-yl)-1H-imidazole-5-sulfonamide N-(azetidin-3-yl)-2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole-5-sulfonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(pyrrolidin-3-ylmethyl)-1H-imidazole-5-sulfona- mide N-(3-aminocyclobutyl)-2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole-5-sulfonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(1-hydroxy-2-methylpropan-2-yl)-1H-imidazole-5- sulfonamide N-(3-aminocyclopentyl)-2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole-5-sulfonamide 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)-N-methylazetidin-3- amine 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(3-(methylamino)propyl)-1H-imidazole-5-sulfona- mide N-(3-aminopropyl)-2-(bis(3-chloro-4-fluorophenyl)methyl)-N-methyl-1H-imidazole-5-sulfo- namide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2-(methylamino)ethyl)-1H-imidazole-5-sulfona- mide140 GRA 4216-foreign filing 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)piperidin-4-amine 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(2-methoxypropyl)-1H-imidazole-5-sulfonamide N-(2-amino-2-methylpropyl)-2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole-5-sulfo- namide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N,N-dimethyl-1H-imidazole-5-sulfonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-cyclopropyl-1H-imidazole-5-sulfonamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(pyrrolidin-1-ylsulfonyl)-1H-imidazole 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-((3,3-difluoropyrrolidin-1-yl)sulfonyl)-1H-imida- zole 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-((3-methoxy-3-methylpyrrolidin-1-yl)sulfonyl)-1H- imidazole 4-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)piperazin-2-one 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(5-oxopyrrolidin-3-yl)-1H-imidazole-5-sulfona- mide 1-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazol-5-yl)sulfonyl)pyrrolidin-3-ol 2-((2-(bis(3-chloro-4-fluorophenyl)methyl)-1H-imidazole)-5-sulfonamido)acetamide 2-(bis(3-chloro-4-fluorophenyl)methyl)-N-(tetrahydrofuran-3-yl)-1H-imidazole-5-sulfona- mide 4-(azetidin-3-ylsulfonyl)-2-[bis(3-chloro-4-fluorophenyl)methyl]-1H-imidazole 2-[bis(3-chloro-4-fluorophenyl)methyl]-4-(1-methylazetidin-3-yl)sulfonyl-1H-imidazole 4-[[2-[bis(3-chloro-4-fluorophenyl)methyl]-1H-imidazol-4-yl]sulfonyl]piperidine 2-[bis(3-chloro-4-fluorophenyl)methyl]-4-pyrrolidin-3-ylsulfonyl-1H-imidazole (2-(bis(3-(difluoromethyl)-4-fluorophenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(me- thyl)-l6-sulfanone (2-(bis(4-chloro-2-methoxyphenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6- sulfanone (2-(bis(4-chloro-3-fluorophenyl)methyl)-5-methyl-1H-imidazol-4-yl)(imino)(methyl)-l6-sul- fanone (2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(methyl-d3)-1H-imidazol-4-yl)(imino)(methyl)-l6- sulfanone (2-(bis(3-chloro-4-fluorophenyl)methyl)-5-cyclopropyl-1H-imidazol-4-yl)(imino)(methyl)-l6- sulfanone (2-(bis(3-chloro-4-fluorophenyl)methyl)-5-ethyl-1H-imidazol-4-yl)(imino)(methyl)-l6-sul- fanone 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-chloro-1H-imidazole-4-sulfonamide (2-(bis(3-chloro-4-fluorophenyl)methyl)-5-chloro-1H-imidazol-4-yl)(imino)(methyl)-l6-sul- fanone 2-(bis(3-chloro-4-fluorophenyl)methyl)-5-(methoxymethyl)-4-(methylsulfonyl)-1H-imidazole 6-(bis(3-chloro-4-fluorophenyl)methyl)-4-methyl-2,5-dihydroimidazo[4,5-e][1,2]thiazine 1,1- dioxide141 GRA 4216-foreign filing 195 7-(bis(3-chloro-4-fluorophenyl)methyl)-3,6-dihydro-2H-imidazo[4,5-f][1,2]thiazepine 1,1-di- oxide 196 7-(bis(3-chloro-4-fluorophenyl)methyl)-3,4,5,6-tetrahydro-2H-imidazo[4,5-f][1,2]thiazepine 1,1-dioxide 197 2-(bis(3-chloro-4-fluorophenyl)methyl)-5,6,7,8-tetrahydro-1H-thiepino[2,3-d]imidazole 4,4- dioxide 198 N-((2-(bis(3-chloro-4-fluorophenyl)methyl)-4-methyl-1H-imidazol-5-yl)methyl)methanesul- fonamide 199 3-chloro-6-((4-chlorophenyl)(4-(methylsulfonyl)-1H-imidazol-2-yl)methyl)-2-(trifluorome- thyl)pyridine 200 (2-((5-chloro-6-(trifluoromethyl)pyridin-2-yl)(4-chlorophenyl)methyl)-1H-imidazol-4- yl)(imino)(methyl)-l6-sulfanone 201 (3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-1H-imidazol-2-yl)(6-(2,2,2-trifluoroethoxy)py- ridin-3-yl)methanol 202 (2-((3-chloro-4-fluorophenyl)(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methyl)-1H-imidazol-4- yl)(imino)(methyl)-l6-sulfanone 203 (2-((3-chloro-4-fluorophenyl)(5-chloro-6-(trifluoromethyl)pyridin-3-yl)methyl)-1H-imidazol- 4-yl)(imino)(methyl)-l6-sulfanone 204 (3-chloro-4-fluorophenyl)(3,3-difluorocyclopentyl)(4-methyl-5-(methylsulfonyl)-1H-imida- zol-2-yl)methanol 205 5-((3-chloro-4-fluorophenyl)(4-methyl-5-(methylsulfonyl)-1H-imidazol-2-yl)methyl)-4-me- thyloxazol-2-amine in the form of the free compound or a physiologically acceptable salt thereof.

14. A pharmaceutical dosage form comprising a compound according to any of claims 1 to 13.

15. The compound according to any of claims 1 to 13 for use in the treatment of pain.

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