Hydroxyl compounds targeting the CCR6 receptor

Abstract

The present invention provides new derivatives having the general formula (I) (I) wherein R1, R2, R3, R4, R5, R6, R7, X1, X2, X3, X4, and X5 are as defined herein, compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds.

Description

[0001] Docket No. P39379 NOVEL HYDROXYL COMPOUNDS BACKGROUND Immune surveillance, the migration of immune cells throughout the body is a tightly regulated process that is involved in many aspects of health and disease. Chemokines, and their corresponding receptors, play critical roles in these trafficking patterns, they are responsible for getting the right cells into the right tissues (Griffith, J. W., Sokol, C. L. & Luster, A. D. (2014). Chemokines and Chemokine Receptors: Positioning Cells for Host Defense and Immunity. Immunology, 32(1), 659–702 and Zlotnik, A. & Yoshie, O. (2012). The Chemokine Superfamily Revisited. Immunity, 36(5), 705–716). Chemokines, or chemotactic cytokines, are a family of around 50 small signaling proteins secreted by a variety of cell populations (David, B. A. & Kubes, P. (2019). Exploring the complex role of chemokines and chemoattractants in vivo on leukocyte dynamics. Immunological Reviews, 289(1), 9–30 and Griffith, J. W., Sokol, C. L. & Luster, A. D. (2014). Chemokines and Chemokine Receptors: Positioning Cells for Host Defense and Immunity. Immunology, 32(1), 659–702). Chemokines are divided into four main subfamilies, called CC, CXC, CX3C and C, based on the location of the canonical cysteine residues in the N-terminal region. Chemokine secretion and diffusion create concentration gradients that direct the migration of cells expressing the corresponding receptors. Chemokine receptors are a family of around 20 seven transmembrane proteins differentially expressed on the surface of immune cells and can be divided into two main subfamilies, the first is called G protein–coupled chemokine receptors, which mediate immune cell trafficking, and the second is called atypical chemokine receptors, which seem to be chemokine scavengers that influence the chemokine gradients. They are also grouped into four subfamilies according to the subfamily of their major chemokine ligands. In some cases, one chemokine can signal through multiple receptors and, in many cases, one receptor can be stimulated by multiple chemokines. These promiscuous interactions makepharmacological intervention of signaling more complicated.CCR6, also called CD196, is a chemokine receptor expressed on a variety of adaptive and innate immune cells including B cells, T cells, dendritic cells and neutrophils. For example, TH17 cells, which play a critical role in the pathogenesis of multiple autoimmune diseases, express CCR6 and this signal has been shown to recruit these cells into inflamed peripheral tissues ( Esplugues, E., Huber, S., Gagliani, N., Hauser, A. E., Town, T., Wan, Y. Y., O’Connor, W., Rongvaux, A., Rooijen, N. V., Haberman, A. M., Iwakura, Y., Kuchroo, V. K., Kolls, J. K., Bluestone, J. A., Herold, K. C. & Flavell, R. A. (2011). Control of TH17 cells occurs in the Small Intestine. Nature, 475(7357), 514–518 and Singh, S. P., Zhang, H. H., Foley, J. F., Hedrick, M. N. & Farber, J. M. (2008). Human T Cells That Are Able to Produce IL-17 Express the Chemokine Receptor CCR6. The Journal of Immunology, 180(1), 214–221). The ligand for CCR6 is CCL20, also called macrophage inflammatory protein 3 alpha (MIP-3 alpha) and liver and activation-regulated chemokine (LARC). The CCR6 / CCL20 pair is somewhat unique because they have only one binding partner and therefore form a pharmacologically selective receptor-ligand pair (Schutyser, E., Struyf, S. & Damme, J. V. (2003). The CC chemokine CCL20 and its receptor CCR6. Cytokine & Growth Factor Reviews, 14(5), 409–426). CCL20 expression and secretion is increased in the presence of inflammatory stimuli. High levels of CCL20 can be found in the inflamed tissue associated with multiple inflammatory autoimmune diseases including psoriatic diseases, asthma, Crohn’s disease, ulcerative colitis, rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis (Richmond, J. M., Strassner, J. P., Essien, K. I. & Harris, J. E. (2019). T-cell positioning by chemokines in autoimmune skin diseases. Immunological Reviews, 289(1), 186–204, Lee, A. Y. & Körner, H. (2014). CCR6 and CCL20: emerging players in the pathogenesis of rheumatoid arthritis. Immunology and Cell Biology, 92(4), 354–358, Raman, D., Sobolik- Delmaire, T. & Richmond, A. (2011). Chemokines in health and disease. Experimental Cell Research, 317(5), 575–589, Pène, J., Chevalier, S., Preisser, L., Vénéreau, E., Guilleux, M.- H., Ghannam, S., Molès, J.-P., Danger, Y., Ravon, E., Lesaux, S., Yssel, H. & Gascan, H. (2008). Chronically Inflamed Human Tissues Are Infiltrated by Highly Differentiated Th17 Lymphocytes. The Journal of Immunology, 180(11), 7423–7430 and Schutyser, E., Struyf, S. & Damme, J. V. (2003). The CC chemokine CCL20 and its receptor CCR6. Cytokine & Growth Factor Reviews, 14(5), 409–426). Genetic linkage, clinical association and preclinical studies highlight a critical role for CCR6 in these inflammatory diseases (Hamburg, J. P. van & Tas, S. W. (2018). Molecular mechanisms underpinning T helper 17 cell heterogeneity and functions in rheumatoid arthritis. Journal of Autoimmunity, 87, 69–81 and Kurkó, J., Besenyei, T., Laki, J., Glant, T. T., Mikecz, K. & Szekanecz, Z. (2013). Genetics of Rheumatoid Arthritis — A Comprehensive Review. Clinical Reviews in Allergy & Immunology, 45(2), 170–179). Forexample, CCR6 gene variants have the highest risk association for Crohn’s disease (CD)amongst the chemokine receptor family (Lee, A. Y. S., Eri, R., Lyons, A. B., Grimm, M. C. & Korner, H. (2013). CC Chemokine Ligand 20 and Its Cognate Receptor CCR6 in Mucosal T Cell Immunology and Inflammatory Bowel Disease: Odd Couple or Axis of Evil Frontiers in Immunology, 4, 194). This high selectivity renders CCR6 an attractive drug target. Selective CCR6 inhibitors would only result in on-target pharmacology. BRIEF SUMMARY A first object of the present invention is a compound of formula (I) wherein X1is CH or N; X2is CH or N; X3is CH or N; X4is O or NH; X5is CH or N; R1is aryl, heterocyclyl, or heteroaryl, wherein aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more R1a; R1ais C1-6alkyl, oxo, cyano, carbamoyl, C1-6haloalkyl, C1-6alkoxy, C1-6alkylcarbamoyl-,C1-6alkoxyC1-6alkyl-, C3‑6cycloalkyl, or heterocyclyl; R2is hydrogen or halogen; R3is hydrogen or halogen; R4is OH; R5is hydrogen or C1-6alkyl; R6is -OR6a, -SR6b, or hydrogen; R6ais C1-6haloalkyl; R6bis C1-6haloalkyl; R7is -OR7a, -SR7b, or hydrogen; R7ais C1-6haloalkyl; R7bis C1-6haloalkyl; provided that R6and R7must be different, and R6or R7is hydrogen, or pharmaceutically acceptable salts thereof. A second object of the present invention is a process of preparation of a compound of formula (I) or (I') as defined herein, or a pharmaceutically acceptable salt thereof, wherein X1is N and R4is OH, comprising: reacting compound of formula (II), wherein R5is as defined herein, with compound of formula (III), wherein X5R6,R7are as defined herein, and X is halogen, to form compound of formula (IV), wherein R5, R6, R7, and X5are as defined herein, reacting said compound of formula (IV) with acid, to form compound of formula (V), wherein R5, R6, R7, and X5are as defined herein, reacting said compound of formula (V) with compound of formula (VI), wherein R 2,R3, X2, X3are as defined herein,

[0002] to form compound of formula (VII), wherein R2, R3, X2, X3, R5, X5, R6, R7are as defined herein, reacting said compound of formula (VII) with compound of formula (VIII), wherein R1is as defined herein, and R9and R10taken together with the oxygen atom to which they are attached, form a 3- to 14- membered heterocyclyl optionally substituted with one or more C1-6alkyl, in particular optionally substituted with four C1-6alkyl, to form compound of formula (I). A third object of the present invention is a process of preparation of a compound of formula (I) or (I') as defined herein, or a pharmaceutically acceptable salt thereof, wherein R1is a N-connected heterocyclyl group comprising: reacting compound of formula (V), wherein R5, R6, R7, and X5are as defined herein, with compound of formula (XI), wherein R2, R3, X2, X3are as defined herein, to form compound of formula (XII), wherein R2, R3, X2, X3, R5, X5, R6, R7are as defined herein, reacting said compound of formula (XII) with compound of formula (XIII), wherein R1is herein, (XIII) to form compound of formula (I). A fourth object of the present invention is a process of preparation of a compound of formula (I) or (I') as defined herein, or a pharmaceutically acceptable salt thereof, wherein X1is CH, and R4is OH, comprising: reacting compound of formula (XIV), with methoxy(methyl)amine hydrochloride to form compound of formula (XV), reacting said compound (XV) with a base, to form compound of formula (XVI), (XVI) reacting said compound of formula (XVI) with a Grubbs catalyst, to form compound (XVII), wherein R5is as defined in any one of claims 1 to 30, reacting said compound (XVII) with compound (XVIII), wherein X2, X3, R2, R3are as defined in any one of claims 1 to 30, (XVIII) to form compound of formula (XIX) wherein X2, X3, R2, R3, R5, are as defined in any one of claims 1 to 30, reacting said compound of formula (XIX) with a reducing agent, to form compound of formula (XX), wherein X2, X3, R2, R3, R5, are as defined in any one of claims 1 to 30, reacting said compound (XX) with an oxidant, to form compound of formula (XXI), wherein X2, X3, R2, R3, R5, are as defined in any one of claims 1 to 30, reacting said compound (XXI) with compound of formula (VIII), wherein R1is as defined in any one of claims 1 to 30, and R9and R10taken together with the oxygen atom to which they are attached, form a 3- to 14- membered heterocyclyl optionally substituted with one or more C1-6alkyl, in particular optionally substituted with four C1-6alkyl, (VIII) to form compound of formula (XXII), wherein X2, X3, R2, R3, R5, R1, are as defined in any one of claims 1 to 30, reacting said compound of formula (XXII) with acid to form compound of formula (XXIII), wherein X2, X3, R2, R3, R5, R1, are as defined in any one of claims 1 to 30, (XXIII) reacting said compound of formula (XXIII) with compound of formula (III), wherein X5, R6, R7are as defined in any one of claims 1 to 30, and X is halogen, (III) to form compound of formula (I). A fifth object of the present invention is a pharmaceutical composition comprising a compound of formula (I) as described above, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. A sixth object of the current invention is a compound of formula (I), as described above, or a pharmaceutically acceptable salt thereof, for use in the treatment, prevention and / or delay of inflammatory autoimmune disease. A seventh object of the current invention is a method for the treatment, prevention and / or delay of progression of inflammatory autoimmune disease, which method comprises administering a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which thisinvention belongs. Although methods and materials similar or equivalent to those describ edherein can be used in the practice or testing of the invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. The nomenclature used in this application is based on IUPAC systematic nomenclature, unless indicated otherwise. Any open valency appearing on a carbon, oxygenor nitrogen atom in the structures herein indicates the presence of a hydrogen atom.DEFINITIONS "Acid" refers to a compound capable of giving proton of Broensted’s definition, dissociating into proton and counter ion in water at 25°C and giving a solution having neutral pH or below. Concrete examples of the acid are phosphoric acid (orthophosphoric acid), sulfuric acid, nitric acid, phosphinic acid, phosphonic acid, diphosphonic acid, hydrochloric acid, pyrophosphoric acid, metaphosphoric acid and nitrous 10 acid. These acids may be used in the form of metal salts, ammonium salts or the like; particularly acid means hydrochloric acid. "C1-6Alkoxy" refers to a C1-6alkyl group, as previously defined, attached to the parent molecular moiety via an oxygen atom. Unless otherwise specified, the alkoxy group contains 1 to 6 carbon atoms (“C1-6-alkoxy”). In some particular embodiments, the alkoxy group contains 1 to 4 carbon atoms. In still other embodiments, the alkoxy group contains 1 to 3 carbon atoms. Some non-limiting examples of alkoxy groups include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy and tert-butoxy. “Amino”, alone or in combination with other groups, refers to NH2. "Aromatic" refers to the conventional idea of aromaticity as defined in the literature, in particular in IUPAC - Compendium of Chemical Terminology, 2ndEdition, A. D.McNaught & A. Wilkinson (Eds). Blackwell Scientific Publications, Oxford (1997)."Aryl" refers to a cyclic aromatic hydrocarbon moiety having a mono-, bi- or tricyclic aromatic ring of 5 to 14 carbon ring atoms (“C5-14-aryl”). Bicyclic aryl ring systems include fused bicyclics having two fused five-membered aryl rings (denoted as 5-5), having a five-membered aryl ring and a fused six-membered aryl ring (denoted as 5-6 and as 6-5), and having two fused six-membered aryl rings (denoted as 6-6). The aryl group can be optionally substituted as defined herein. Examples of aryl moieties include, but are not limited to, phenyl, naphthyl, phenanthryl, fluorenyl, indenyl, pentalenyl, azulenyl, and the like. In particular aryl means phenyl. "Base" refers to a chemical compound having at least one electronegative group capable of accepting a hydrogen ion. "C1-6alkyl" refers to a saturated linear (i.e. unbranched) or branched univalent hydrocarbon chain or combination thereof, having the number of carbon atoms designated (i.e., C1-6 means one to ten carbon atoms). Particular C1-6alkyl groups are those having 1 to 6 carbon atoms, having 2 to 6 carbon atoms (a “C2-6alkyl”), or having 1 to 4 carbon atoms (a “C1-4alkyl”). Examples of C1-6alkyl group include, but are not limited to, groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, homologs and isomers of, for example, n-pentyl, n-hexyl, and the like. “Cyano”, alone or in combination with other groups, refers to CN (i.e. nitrile). "Cycloalkyl" refers to a saturated or partially unsaturated carbocyclic moiety having mono-, bi- (including bridged bicyclic and cycloalkyl spiro moieties) or tricyclic rings and 3 to 10 carbon atoms i.e., (C3-C10)cycloalkyl) in the ring. The cycloalkyl moiety can optionally be substituted with one or more substituents. In particular aspects cycloalkyl contains from 3 to 8 carbon atoms (i.e., (C3-C8)cycloalkyl). In other particular aspects cycloalkyl contains from 3 to 6 carbon atoms (i.e., (C3-C6)cycloalkyl). Examples of cycloalkyl moieties include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and partially unsaturated (cycloalkenyl) derivatives thereof (e.g. cyclopentenyl, cyclohexenyl, and cycloheptenyl), bicyclo[3.1.0]hexanyl, bicyclo[3.1.0]hexenyl, bicyclo[3.1.1]heptanyl, bicyclo[3.1.1]heptenyl and bicyclo[1.1.1]pentane. The cycloalkyl moiety can be attached in a “spiro-cycloalkyl” or“cycloalkyl spiro” fashion such as “spirocyclopropyl”."Halo" or “Halogen” means fluoro, chloro, bromo or iodo, particularly chloro or fluoro. "Haloalkoxy" refers to an alkoxy group in which at least one Halogen takes the place of each H in the hydrocarbon making up the C1-6alkyl moiety of the alkoxy group. An example of a haloalkoxy group is difluoromethoxy (-OCHF2), trifluoromethoxy (-OCF3). "Heteroaryl" refers to an aromatic heterocyclic mono-, bi- or tricyclic ring system of 5 to 14 ring atoms, preferably from 5 to 10 ring atoms, more preferably from 5 to 6 ring atoms, comprising 1, 2, 3 or 4 heteroatoms selected from N, O and S, the remaining ring atoms being carbon. In some aspects, monocyclic heteroaryl rings may be 5-6 membered. Bicyclic heteroaryl ring systems include fused bicyclics having two fused five-membered heteroaryl rings (denoted as 5-5), having a five-membered heteroaryl ring and a fused six- membered heteroaryl ring (denoted as 5-6 and 6-5), and having two fused six-membered heteroaryl rings (denoted as 6-6). The heteroaryl group can be optionally substituted as defined herein. Examples of heteroaryl moieties include indazolyl, indolyl, isoindolinyl, triazolopyridinyl, imidazopyridinyl, imidazopyrazinyl, indolinyl, pyridyl, triazolopyridazinyl, isoquinolinyl, pyridazinyl, triazolopyrazinyl, pyrrolotriazinyl, spirocyclopropaneindolinyl, pyrrolyl, furanyl, thienyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyridinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, triazinyl, isoxazolyl, benzofuranyl, isothiazolyl, benzothienyl, benzothiophenyl, indolyl, aza-indolyl, isoindolyl, isobenzofuranyl, benzimidazolyl, benzoxazolyl, benzoisoxazolyl, benzothiazolyl, benzoisothiazolyl, benzooxadiazolyl, benzothiadiazolyl, benzotriazolyl, purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, pyrrolopyridinyl, furopyridinyl, thienopyridinyl, pyrrolopyridazinyl, pyrrolopyrimidinyl, pyrrolopyrazinyl, thienopyridazinyl, thienopyrimidinyl, thienopyrazinyl, furopyridazinyl, furopyrimidinyl, and furopyrazinyl. Particular examples of heteroaryl are triazolopyrazinyl, triazolopyridinyl or imidazopyridinyl, Even more particularly heteroaryl is [1,2,4]triazolo[4,3-a]pyridin-6-yl. "Heterocycle" or "heterocyclyl" refer to a 3, 4, 5, 6, 7, 8, 9, 10-membered monocyclic, 7, 8, 9 and 10-membered bicyclic (including bridged bicyclic and cycloalkyl spiro moieties) or 10, 11, 12, 13, 14 and 15-membered bicyclic heterocyclic moiety that is saturated or partially unsaturated, and has one or more (e.g., 1, 2, 3 or 4) heteroatoms selected from oxygen, nitrogen and sulfur in the ring with the remaining ring atoms being carbon. In some aspects, the heterocycle is a heterocycloalkyl. In particular aspects heterocycle or heterocyclyl refers to a 4, 5, 6 or 7-membered heterocycle. When used in reference to a ring atom of a heterocycle, a nitrogen or sulfur may also be in an oxidized form, and a nitrogen may be substituted with one or more (C1-C6)C1-6alkyl or groups. The heterocycle can be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure. Any of the heterocycle ring atoms can be optionally substituted with one or more substituents described herein. Examples of such saturated or partially unsaturated heterocycles include, without limitation, tetrahydrofuranyl, tetrahydrothienyl, pyrrolidinyl, pyrrolidonyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, pyrrolidine 1-oxide, N- hydroxypiperidine, 1-methylpyrrolidine N-oxide, diazirinyl and quinuclidinyl. The term heterocycle also includes groups in which a heterocycle is fused to one or more aryl, heteroaryl, or cycloalkyl rings, such as indolinyl, 3H-indolyl, chromanyl, azabicyclo[2.2.1]heptanyl, azabicyclo[3.1.0]hexanyl, azabicyclo[3.1.1]heptanyl, octahydroindolyl, or tetrahydroquinolinyl. Particular examples of heterocycle are triazaspirodecanyl, diazaspirodecanyl or azaspirononanyl. More particular examples of heterocycle are diazaspirodecanyl or azaspirononanyl The terms "inflammatory bowel disease" or "IBD" means several diseases associated with inflammation of the small intestine, large intestine (colon), rectum or anus (anal sphincter), and may particularly include ulcerative colitis and Crohn's disease, including proctitis in both cases. As used in the present context, the term "IBD" also includes gastrointestinal (GI) tract cancer, which is a likely result of Gl tract inflammation. As used in this specification, the terms "gastrointestinal tract" or "Gl tract" mean the small intestine,large intestine (colon), rectum or anus (anal sphincter)."Moiety" and “Substituent” refer to an atom or group of chemically bonded atoms that is attached to another atom or molecule by one or more chemical bonds thereby forming part of a molecule. When indicating the number of substituents, the term “one or more” refers to the range from one substituent to the highest possible number of substitution, i.e. replacement of one hydrogen up to replacement of all hydrogens by substituents, in particular wherein “one or more” refers to one, two or three, most particularly “one or more” refers to one or two. "Obstructive pulmonary disease" refers to any disease that causes the airways of the lungs to become narrow or blocked so that a patient cannot exhale completely. Because of damage to the lungs or narrowing of the airways inside the lungs, exhaled air comes out more slowly than normal. At the end of a full exhalation, an abnormally high amount of air may still remain in the lungs. Examples of obstructive pulmonary diseases are asthma,bronchiectasis, bronchitis and chronic obstructive pulmonary disease (COPD)."Optional" or “optionally” means that the subsequently described event or circumstance may but need not occur, and that the description includes instances where the event or circumstance occurs and instances in which it does not. For example, "aryl group optionally substituted with a C1-6alkyl group" means that the C1-6alkyl may but need not bepresent, and the description includes situations where the aryl group is substituted with a C 1-6alkyl group and situations where the aryl group is not substituted with the C 1-6alkyl group."Optionally substituted" means unsubstituted or substituted. Generally these substituents can be the same or different. "Oxidant" refers to one or more suitable electron acceptors or electron sharers and may be an element, combination of elements, a compound, or combination of compounds including reducible compounds, and is a vapor, solid or liquid at the process conditions. An example of oxidant is mCPBA (meta-Chloroperoxybenzoic acid). “Oxo”, alone or in combination with other groups, refers to =O. "Pharmaceutically acceptable salt" refers to those salts which retain the biological effectiveness and properties of the free bases or free acids, which are not biologically or otherwise undesirable. The salts are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, particularly hydrochloric acid, and organic acids such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p- toluenesulfonic acid, salicylic acid, N-acetylcystein. More particularly pharmaceutically acceptable salts of compounds of formula (I) are the salts of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid and methanesulfonic acid. "Prophylaxis" as used herein includes: preventing or delaying the appearance of clinical symptoms of the state, disorder or condition developing in a mammal and especially a human that may be afflicted with or predisposed to the state, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disorder or condition. "Protecting group" refers to the group which selectively blocks a reactive site in a multifunctional compound such that a chemical reaction can be carried out selectively atanother unprotected reactive site in the meaning conventionally associated with it insynthetic chemistry. Protective groups can be removed at the appropriate point. Exemplary protective groups are Amino-protective groups, carboxy-protective groups or hydroxy- protective groups. Particular protective groups are the tert-butoxycarbonyl (Boc), benzyloxycarbonyl (Cbz), fluorenylmethoxycarbonyl (Fmoc) and benzyl (Bn). Further particular protective groups are the tert-butoxycarbonyl (Boc) and thefluorenylmethoxycarbonyl (Fmoc). More particular protective group is the tert -butoxycarbonyl (Boc). Exemplary protective groups and their application in organic synthesis are described, for example, in “Protective Groups in Organic Chemistry” by T. W.Greene and P. G. M. Wutts, 5th Ed., 2014, John Wiley & Sons, N.Y."Substituted" refers to the replacement of at least one of hydrogen atoms of a compound or moiety with another substituent or moiety. Examples of such substituents include, without limitation, Halogen, -OH, -CN, oxo, alkoxy, C1-6alkyl, alkylene, aryl, heteroaryl, haloalkyl, haloalkoxy, cycloalkyl and heterocycle. For example, the term “haloalkyl” refers to the fact that one or more hydrogen atoms of a C1-6alkyl (as defined below) is replaced by one or more Halogen atoms (e.g., trifluoromethyl, difluoromethyl, fluoromethyl, chloromethyl, etc.). In one aspect, substituted as used herein can refer to replacement of at least one hydrogen atom of a compound or moiety described herein with Halogen or C1-6alkyl. "Therapeutically effective amount" refers to an amount of a compound or molecule of the present invention that, when administered to a subject, (i) treats or prevents the particular disease, condition or disorder, (ii) attenuates, ameliorates or eliminates one ormore symptoms of the particular disease, condition, or disorder, or (iii) prevents or delaysthe onset of one or more symptoms of the particular disease, condition or disorder described herein. The therapeutically effective amount will vary depending on the compound, the disease state being treated, the severity of the disease treated, the age and relative health of the subject, the route and form of administration, the judgement of the attending medical or veterinary practitioner, and other factors. "Therapeutically inert carrier" refers to any ingredient having no therapeutic activity and being non-toxic such as disintegrators, binders, fillers, solvents, buffers, tonicity agents, stabilizers, antioxidants, surfactants or lubricants used in formulating pharmaceutical products. DETAILED DESCRIPTION In one embodiment, the present invention relates a compound of formula (I) wherein X1is CH or N; X2is CH or N; X3is CH or N; X4is O or NH; X5is CH or N; R1is aryl, heterocyclyl, or heteroaryl, wherein aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more R1a; R1ais C1-6alkyl, oxo, cyano, carbamoyl, C1-6haloalkyl, C1-6alkoxy, C1-6alkylcarbamoyl-,C1-6alkoxyC1-6alkyl-, C3‑6cycloalkyl, or heterocyclyl; R2is hydrogen or halogen; R3is hydrogen or halogen; R4is OH; R5is hydrogen or C1-6alkyl; R6is -OR6a, -SR6b, or hydrogen; R6ais C1-6haloalkyl; R6bis C1-6haloalkyl; R7is -OR7a, -SR7b, or hydrogen; R7ais C1-6haloalkyl; R7bis C1-6haloalkyl; provided that R6and R7must be different, and R6or R7is hydrogen, or pharmaceutically acceptable salts thereof. A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein X 1 isCH. A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein X 1 is N.A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein X 4 is O.A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein X 5 isCH. A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein X 5 is N.A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein X1is N, X2is CH, X3is CH, X4is O, and X5is CH. A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, whereinX1is N, X2is CH, X3is CH, X4is O, and X5is N. A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein R 1 isheterocyclyl, or heteroaryl, wherein heterocyclyl, and heteroaryl, are optionally substituted with one or more R1a. A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein R 1 istriazolopyrazinyl, triazolopyridinyl, imidazopyridinyl, triazaspirodecanyl, diazaspirodecanyl, or azaspirononanyl, wherein triazolopyrazinyl, triazolopyridinyl, imidazopyridinyl, triazaspirodecanyl, diazaspirodecanyl, and azaspirononanyl are optionally substituted with one or more R1a.A particular embodiment of the present invention relates to a compound of formula (I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein R1is triazolopyrazinyl, triazolopyridinyl, imidazopyridinyl, diazaspirodecanyl, or azaspirononanyl, wherein triazolopyrazinyl, triazolopyridinyl, imidazopyridinyl, diazaspirodecanyl, and azaspirononanyl are optionally substituted with one or more R1a. A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein R 1 istriazolopyrazinyl, triazolopyridinyl, imidazopyridinyl, triazaspirodecanyl, diazaspirodecanyl, or azaspirononanyl, wherein triazolopyrazinyl, triazolopyridinyl, imidazopyridinyl, triazaspirodecanyl, diazaspirodecanyl, and azaspirononanyl are optionallysubstituted with one or two isopropyl, difluoromethyl, methyl, oxo, or methoxy. A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein R 1 istriazolopyrazinyl, triazolopyridinyl, imidazopyridinyl, diazaspirodecanyl, or azaspirononanyl, wherein triazolopyrazinyl, triazolopyridinyl, imidazopyridinyl, diazaspirodecanyl, and azaspirononanyl are optionally substituted with one or two isopropyl, difluoromethyl, methyl, oxo, or methoxy. A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein R 1 istriazolopyridinyl optionally substituted with one R1a. A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein R 1a isC1-6alkyl, oxo, C1-6haloalkyl, C1-6alkoxy. A particular embodiment of the present invention relates to a compound of formula (I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein R1ais C1-6alkyl, more particularly where R1ais methyl. A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein R 2 ishydrogen. A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein R 3 ishydrogen. A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein R 5 ishydrogen. A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein R 6 is -SCF3, -OCF3, -OCHF2, or hydrogen. A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein R 6 is -SCF3, or -OCF3. A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein R 6 is -SCF3.A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein R 6b is -CF3. A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein R 7 is -OCF3, -SCF3, -OCHF2, or hydrogen. A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein R 7 ishydrogen. A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein R 7a is -CF3, or -CHF2. A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein R 7b is -CF3. A particular embodiment of the present invention relates to a compound of formula (I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein the compound is of formula (I')

[0003] or a pharmaceutically acceptable salt thereof wherein R1, R2, R3, R5, R6, R7, X1, X2, X3, X4, and X5are as defined herein. A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, whereinX1is N, X2is CH, X3is CH, X4is O, X5is N, R1is heterocyclyl, or heteroaryl, wherein heterocyclyl, and heteroaryl, are optionally substituted with one or more R1a, R1ais C1-6alkyl, oxo, C1-6haloalkyl, C1-6alkoxy, R2is hydrogen, R3is hydrogen, R4is OH, R5is hydrogen, R6is -SCF3, and R7is hydrogen. A particular embodiment of the present invention relates to a compound of formula(I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, whereinX1is N, X2is CH, X3is CH, X4is O, X5is N, R1is triazolopyridinyl optionally substituted with one R1a, R1ais C1-6alkyl, R2is hydrogen, R3is hydrogen, R4is OH, R5is hydrogen, R6is -SCF3, and R7is hydrogen. A particular embodiment of the present invention relates to a compound of formula (I') (I') X1is N, X2is CH, X3is CH, X4is O, X5is N, R1is triazolopyridinyl optionally substituted with one R1a, R1ais C1-6alkyl, R2is hydrogen, R3is hydrogen, R4is OH, R5is hydrogen, R6is -SCF3, and R7is hydrogen, or a pharmaceutically acceptable salt thereof, A particular embodiment of the present invention relates to a compound of formula (I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, (3S,4R)-1-(4- {3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl}benzenesulfonyl)-4-({4- [(trifluoromethyl)sulfanyl]phenyl}Amino)piperidin-3-ol; (3S,4R)-1-{4-[3-(propan-2-yl)imidazo[1,2-a]pyridin-6-yl]benzenesulfonyl}-4-({4- [(trifluoromethyl)sulfanyl]phenyl}Amino)piperidin-3-ol; (3S,4R)-1-(4-{3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl}benzenesulfonyl)-4-({5- [(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol; (3S,4R)-1-{4-[3-(propan-2-yl)imidazo[1,2-a]pyridin-6-yl]benzenesulfonyl}-4-({5- [(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol; (3S,4R)-1-{4-[3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyrazin-6-yl]benzenesulfonyl}-4-({5- [(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol; (3S,4R)-1-{4-[3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]benzenesulfonyl}-4-({5- [(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol; (3S,4R)-1-{4-[8-methyl-3-(propan-2-yl)imidazo[1,2-a]pyridin-6-yl]benzenesulfonyl}-4-({5- [(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol; (3S,4R)-1-{4-[3-(difluoromethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]benzenesulfonyl}-4- ({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol; 8-(4-{[(3S,4R)-3-hydroxy-4-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin- 1-yl]sulfonyl}phenyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione; (3S,4R)-1-(4-{2-methoxy-7-azaspiro[3.5]nonan-7-yl}benzenesulfonyl)-4-({5- [(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol; 8-(4-{[(3S,4R)-3-hydroxy-4-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin- 1-yl]sulfonyl}phenyl)-2,8-diazaspiro[4.5]decan-1-one; (1R,2R,5R)-5-{4-[3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]benzenesulfonyl}-2- ({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)cyclohexan-1-ol; (1R,2R,5R)-5-(4-{3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl}benzenesulfonyl)-2-({5- [(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)cyclohexan-1-ol; (1R,2R,5R)-5-(4-{imidazo[1,2-a]pyridin-6-yl}benzenesulfonyl)-2-({5- [(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)cyclohexan-1-ol; (1R,2R,5R)-5-{4-[8-methyl-3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6- yl]benzenesulfonyl}-2-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)cyclohexan-1-ol; (1S,2R,5R)-5-{4-[3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]benzenesulfonyl}-2- ({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)cyclohexan-1-ol. A particular embodiment of the present invention relates to a compound of formula (I) or (I') as described herein, or a pharmaceutically acceptable salt thereof, wherein the compound is (3S,4R)-1-(4-{3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl}benzenesulfonyl)-4- ({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol. Further objects of the present invention are all forms of optically pure enantiomers, racemates or diastereomeric mixtures for compounds of formula (I) or (I'). Process of manufacturing Processes for the manufacture of compounds of formula (I), or pharmaceutically acceptable salt thereof, as described herein are also an object of the invention. The present invention provides a process of preparation of a compound as described herein, or a pharmaceutically acceptable salt thereof, wherein X1is N and R4is -OH, comprising: reacting compound of formula (II), wherein R5is as defined herein, (II) with compound of formula (III), wherein X5, R6, R7are as defined herein, and X is halogen, to form compound of formula (IV), wherein R5, R6, R7, and X5are as defined herein, reacting said compound of formula (IV) with acid, to form compound of formula (V), wherein R5, R6, R7, and X5are as defined herein, reacting said compound of formula (V) with compound of formula (VI), wherein R 2,R3, X2, X3are as defined herein,

[0004] to form compound of formula (VII), wherein R2, R3, X2, X3, R5, X5, R6, R7are as defined herein, reacting said compound of formula (VII) with compound of formula (VIII), wherein R1is as defined herein, and R9and R10taken together with the oxygen atom to which they are attached, form a 3- to 14- membered heterocyclyl optionally substituted with one or more C1-6alkyl, in particular optionally substituted with four C1-6alkyl, to form compound of formula (I). The present invention provides a process of preparation of a compound as described herein, or a pharmaceutically acceptable salt thereof, wherein R1is a N-connected heterocyclyl group comprising: reacting compound of formula (V), wherein R5, R6, R7, and X5are as defined herein, with compound of formula (XI), wherein R2, R3, X2, X3are as defined herein, to form compound of formula (XII), wherein R2, R3, X2, X3, R5, X5, R6, R7are as defined herein, reacting said compound of formula (XII) with compound of formula (XIII), wherein R1is herein, (XIII) to form compound of formula (I). The present invention provides a process of preparation of a compound as described herein, or a pharmaceutically acceptable salt thereof, wherein X1is CH, and R4is OH, comprising: reacting compound of formula (XIV), with methoxy(methyl)amine hydrochloride to form compound of formula (XV), reacting said compound (XV) with a base, to form compound of formula (XVI), (XVI) reacting said compound of formula (XVI) with a Grubbs catalyst, to form compound (XVII), wherein R5is as defined in any one of claims 1 to 30, reacting said compound (XVII) with compound (XVIII), wherein X2, X3, R2, R3are as defined in any one of claims 1 to 30, (XVIII) to form compound of formula (XIX) wherein X2, X3, R2, R3, R5, are as defined in any one of claims 1 to 30, reacting said compound of formula (XIX) with a reducing agent, to form compound of formula (XX), wherein X2, X3, R2, R3, R5, are as defined in any one of claims 1 to 30, reacting said compound (XX) with an oxidant, to form compound of formula (XXI), wherein X2, X3, R2, R3, R5, are as defined in any one of claims 1 to 30, reacting said compound (XXI) with compound of formula (VIII), wherein R1is as defined in any one of claims 1 to 30, and R9and R10taken together with the oxygen atom to which they are attached, form a 3- to 14- membered heterocyclyl optionally substituted with one or more C1-6alkyl, in particular optionally substituted with four C1-6alkyl, (VIII) to form compound of formula (XXII), wherein X2, X3, R2, R3, R5, R1, are as defined in any one of claims 1 to 30, reacting said compound of formula (XXII) with acid to form compound of formula (XXIII), wherein X2, X3, R2, R3, R5, R1, are as defined in any one of claims 1 to 30, (XXIII) reacting said compound of formula (XXIII) with compound of formula (III), wherein X5, R6, R7are as defined in any one of claims 1 to 30, and X is halogen, (III) to form compound of formula (I). General methods of preparation The compounds described herein, including compounds of general Formula (I) , canbe readily prepared according to the following reaction schemes and Examples, or modifications thereof, using readily available starting materials, reagents, and conventional synthesis procedures. Many of the reactions can also be carried out under microwave conditions or using conventional heating or utilizing other technologies such as solid phase reagents / scavengers or flow chemistry. In these reactions, it is also possible to make use of variants which are themselves known to those skilled in the art but are not mentioned in greater detail. For Example, where specific acids, bases, reagents, coupling agents, solvents, etc. are mentioned, it is understood that other suitable acids, bases, reagents, coupling agents, solvents etc. may be used and are included within the scope of the present invention. Furthermore, other methods for preparing compounds of the invention will be readily apparent to a person of ordinary skill in the art in light of the following reaction schemes and Examples. In cases where synthetic intermediates and final products contain potentially reactive functional groups, for Example Amino, hydroxyl, thiol and carboxylic acid groups that may interfere with the desired reaction, it may be advantageous to employ protected forms of the intermediate. Methods for the selection, introduction, and subsequent removal of protecting groups are well known to those skilled in the art. The compounds obtained by using the general reaction sequences may be of insufficient purity. The compounds can be purified by using any of the methods of purification of organic compounds, for Example, crystallization or silica gel, alumina or C18 column chromatography, using different solvents in suitable ratios. All possible stereoisomers are envisioned within the scope of the invention. In the discussion below variables have the meaning indicated above unless otherwise indicated. All final compounds have been characterized using for example LC- MS, NMR and / or Specific Optical Rotation. The abbreviations used in these experimental details are listed below and additionalones should be considered known to a person skilled in the art of synthetic chemistry.Abbreviations used herein are as follow: r.t.: room temperature; DMF: Dimethyl formamide; DiPEA: Diisopropylethylamine; DMAP: 4-(dimethylamino)pyridine; TFA: Trifluoroacetic acid; THF: Tetrahydrofuran; DMSO: Dimethylsulfoxide; EtOH: Ethanol; TLC: Thin Layer Chromatography; mCPBA: 3-chloroperbenzoic acid; MeOH: Methanol; HOAc: Acetic acid; NMP: N-methylpyrrolidinone, KOAc: Potassium acetate; N: normal; Josiphos SL J009-1: cyclopentane;ditert-butyl-[(1R)-1-(2- dicyclohexylphosphanylcyclopentyl)ethyl]phosphane;iron; FBS: Fetal Bovine Serum; MW384: MicroWell 384; NaOtBu: Sodium tert-Butoxide; Pd(OAc)2: Palladium(II) Acetate; Pd(dppf)Cl2: Dichlorobis(diphenylphosphinoferrocene)palladium(II); Pd(PPh3)4: Tetrakis(triphenylphosphine)palladium(0); HATU: 1-[Bis(dimethylamino)methylene]-1H- 1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate; DIPEA: N,N- Diisopropylethylamine; NMR: Nuclear Magnetic Resonance; Hz: Hertz; DMEM: Dulbecco's Modified Eagle Medium; CREB: cAMP Response Element-Binding Protein; CRE: cAMP Response Element; LC-MS: Liquid Chromatography-Mass Spectrometry; MS(ES+): Mass Spectrometry (Electrospray Positive); RPMI1640: Roswell Park Memorial Institute 1640 Medium; pen / strep: Penicillin / Streptomycin; SiO2: Silicon Dioxide; CH2Cl2: Dichloromethane; °C: Degrees Celsius; KF: Potassium Fluoride; mg: Milligram; MgSO4: Magnesium Sulfate; NaHCO3: Sodium Bicarbonate; NaOH: Sodium Hydroxide; NaBH4: Sodium Borohydride; HCl: Hydrochloric Acid; K2CO3: Potassium Carbonate; CH3CN: Acetonitrile; TEA: Triethylamine; DCM: Dichloromethane; C18: Octadecylsilane (used in chromatography); mL: Milliliter; Et3N: Triethylamine. If a chemical compound is referred to using both a chemical structure and a chemical name, and an ambiguity exists between the structure and the name, the structure predominates. General procedures Scheme 1:

[0005] Conditions: i) Pd(OAc)2, pyridyl halide (III), NaOtBu, Josiphos SL J009-1, THF, 100 °C; ii) 5N HCl in 2-propanol, CH2Cl2, r.t. iii) 4-bromosulfonylchloride (VI), Et3N, CH2Cl2, r.t.; iv) Pd(dppf)Cl2, Bis(pinacolato)diboron, KOAc, 1,4-dioxane, 100 °C; v) R1-Br (X), NaHCO3, Pd(PPh3)4, dioxane / water, 100 °C; vi) R1-boronic acid / ester (VIII), Pd(PPh3)4, NaHCO3, dioxane / water, 110 °C. Scheme 1 describes a route to synthesize derivatives of the invention having formula (I), when X1is N and R4is OH. tert-Butyl 4-Amino-3-hydroxypiperidine-1-carboxylate derivatives of formula (II) can be converted into derivatives of formula (IV), under Buchwald conditions, using the appropriate aryl halide (III), wherein R6and R7have the meaning as previously described, using for example Josiphos SL J009-1, Pd(OAc)2 and a suitable base e.g. NaOtBu. Derivatives of formula (IV), can be converted, after removing the Boc-group under acidic conditions, using for example TFA, into the 1-(4-bromobenzenesulfonyl)-N- phenylpiperidin-4-amine derivatives of formula (VII) by reaction of the corresponding piperidine derivatives of formula (V), wherein R5, R6and R7have the meaning as previously described, with 4-bromobenzene-1-sulfonyl chloride derivatives of formula (VI), wherein X2, X3, R2and R3have the meaning as previously described, using for example triethyl amine as the base. Finally, derivatives of Formula (I), wherein X1is N, R4is OH, X2, X3, X5, R1, R2, R3, R5, R6and R7have the meaning as previously described, can be prepared, either by direct coupling of derivatives of formula (VII) with commercially available boronic acids or boronic esters of formula (VIII), wherein R1, R9and R10are as defined previously, under Suzuki conditions using for example Pd(PPh3)4and NaHCO3in dioxane / water mixture or, by first converting piperidine derivatives of formula (VII) into the corresponding boronic ester derivatives of formula (IX), which then can be reacted under Suzuki conditions, with R1-halides of formula (X), wherein R1has the meaning as previously described. Scheme 2: Conditions: i) 4-fluorobenzenesulfonyl chloride (XI), triethyl amine, CH2Cl2, r.t.; ii) Heterocycle (XIII), K2CO3, NMP, 120 °C. Scheme 2 describes a route to synthesize derivatives of the invention having Formula (I), when R1is a N-connected heterocyclic group. N-arylpiperidin-4-amine derivatives of formula (V), wherein X5, R5, R6and R7have the meaning as previously described, can be converted into the 1-(4-fluorobenzenesulfonyl)- N-arylpiperidin-4-amine derivatives of formula (XII) by reaction with 4-fluorobenzene-1- sulfonyl chloride derivatives of formula (XI), wherein X2, X3, R2and R3have the meaning as previously described, using for example triethyl amine as the base. In the final step, an NH-heterocyclic group (XIII) can be coupled, under basic conditions, to give the corresponding derivatives of Formula (I), wherein X1is N, X4is O, R4is OH and X2, X3, X5, R1, R2, R3, R5, R6and R7have the meaning as previously described. Scheme 3: Naoh (Conditions: i) methoxy(methyl)amine hydrochloride, DIPEA, DMF, HATU, r.t.; ii) vinyl magnesium bromide, THF, 0 °C; iii) Grubbs Catalyst, CH2Cl2, r.t; iv) 4- bromothiophenol (XVIII), Et3N, CH2Cl2, r.t.; v) NaBH4. CH3OH, 0 °C; vi) mCPBA, CH2Cl2, r.t.; vii) R1-boronic acid / ester (VIII), Pd(PPh3)4, NaHCO3, dioxane / water, 100 °C; viii) TFA, 65 °C; ix) DMSO, DIPEA, KF, pyridyl halide (III), 100 °C. Scheme 3 describes a route to synthesize derivatives of the invention having formula (I), when X1is CH and R4is OH. N-protected (6R)-6-aminocyclohex-2-en-1-one (XVII), wherein R5has the meaning as previously described, can be obtained from commercially available N-protected (2R)-2- aminohex-5-enoic acid (XIV). Conversion of compound (XIV) into the corresponding Weinreb amide (XV), followed by a reaction with vinyl magnesium bromide gives the N- protected (4R)-4-aminoocta-1,7-dien-3-one (XVI), which then can be converted into N- protected (6R)-6-aminocyclohex-2-en-1-one (XVII), by an olefin metathesis ring closure reaction, using for example Grubbs catalyst 2ndgeneration. This 6-aminocyclohex-2-en-1- one (XVII) can undergo a nucleophilic 1,4-addition with 4-bromobenzene-1-thiol derivatives of formula (XVIII), wherein R2, R3, X2and X3have the meaning as previously described, to give 2-Amino-5-(phenylsulfanyl)cyclohexan-1-one derivatives of formula (XIX). Using for example NaBH4as the reducing agent, derivatives of formula (XIX) can be converted into the N-protected 2-Amino-5-(phenylsulfanyl)cyclohexan-1-ol derivatives of formula (XX). The sulfanyl moiety can be oxidized, by using e.g. mCPBA, to give the sulfone derivatives of formula (XXI), wherein R2, R3, R5, X2and X3have the meaning as previously described. Derivatives of formula (XXI) can be converted, by reaction with suitable boronic acids or boronic esters of formula (VIII), wherein R1, R9and R10are as defined previously, under Suzuki conditions, using for example Pd(PPh3)4 as the catalyst and a suitable base e.g. K2CO3, into derivatives of compound (XXII), wherein X2, X3, R1, R2, R3and R5have the meaning as previously described. Finally, derivatives of formula (XXII) can be converted into derivatives of formula (XXIII), under acidic conditions, which can be converted via a nucleophilic substitution reaction with the appropriate aryl halide (III), wherein X5is N and R6and R7have the meaning as previously described, into derivatives of Formula (I), wherein X1is CH, X5= N, R4is OH, X2, X3, R1, R2, R3, R5, R6and R7have the meaning as previously described. Pharmaceutical compositions and administration Another object of the present invention is a pharmaceutical composition comprising a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. Another embodiment of the present invention is a pharmaceutical composition comprising a compound as described herein, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. Another embodiment of the present invention is the pharmaceutical composition asdescribed herein, further comprising an additional therapeutic agent.Indications The compounds of formula (I), (I') as described herein, can be used in an effective amount to treat a subject, in particular a human, affected by an inflammatory autoimmune disease. In one embodiment of the present invention is the compound as described herein, ora pharmaceutically acceptable salt thereof, for use as therapeutically active substance.In one embodiment of the present invention is the compound as described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment, prevention and / or delay of an inflammatory autoimmune disease. In one embodiment of the present invention is the compound as described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment, prevention and / or delayof progression of psoriatic diseases, asthma, Inflammatory Bowel Diseases (IBD) , Crohn’sdisease, Obstructive Lung Diseases ulcerative colitis, rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis. In one embodiment of the present invention is the compound as described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment, prevention and / or delay of progression of psoriatic diseases, asthma, Crohn’s disease, ulcerative colitis, rheumatoidarthritis, systemic lupus erythematosus and multiple sclerosis.In one embodiment of the present invention is the compound as described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment, prevention and / or delay of progression of psoriatic diseases, asthma, Crohn’s disease, ulcerative colitis, rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis. In one embodiment of the present invention is the compound as described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for thetreatment, prevention and / or delay of an inflammatory autoimmune disease.In a further embodiment, the present invention provides a method for the treatment, prevention and / or delay of progression of an inflammatory autoimmune disease, which method comprises administering a therapeutically effective amount of a compound asdescribed herein, or a pharmaceutically acceptable salt thereof.In a further embodiment, the present invention provides a method for the treatment, prevention and / or delay of progression of psoriatic diseases, asthma, Inflammatory Bowel Diseases (IBD), Crohn’s disease, Obstructive Lung Diseases ulcerative colitis, rheumatoid arthritis, systemic lupus erythematosus or multiple, which method comprises administering a therapeutically effective amount of a compound as described herein, or a pharmaceutically acceptable salt thereof. By the term “treatment” or "treating" and grammatical variations thereof as used herein, is meant therapeutic therapy. In reference to a particular condition, treating means: (1) to ameliorate the condition or one or more of the biological manifestations of the condition, (2) to interfere with (a) one or more points in the biological cascade that leads to or is responsible for the condition or (b) one or more of the biological manifestations of the condition, (3) to alleviate one or more of the symptoms, effects or side effects associated with the condition or treatment thereof, or (4) to slow the progression of the condition or one or more of the biological manifestations of the condition. Prophylactic therapy using the methods and / or compositions of the invention is also contemplated. The skilled artisan will appreciate that "prevention" is not an absolute term. In medicine, "prevention" is understood to refer to the prophylactic administration of a drug to substantially diminish the likelihood or severity of a condition or biological manifestation thereof, or to delay the onset of such condition or biological manifestation thereof. Prophylactic therapy is appropriate, for example, when a subject is considered at high risk for developing psoriatic diseases, asthma, Inflammatory Bowel Diseases (IBD), Crohn’s disease, Obstructive Lung Diseases ulcerative colitis, rheumatoid arthritis, systemic lupus erythematosus or multiple, such as when a subject has a strong family history of psoriatic diseases, asthma, Inflammatory Bowel Diseases (IBD), Crohn’s disease, Obstructive Lung Diseases ulcerative colitis, rheumatoid arthritis, systemic lupus erythematosus or multiple. Examples Experimental part As depicted in the Examples below, in certain exemplary embodiments, compounds are prepared according to the following general procedures. It will be appreciated that, although the general methods depict the synthesis of certain compounds of the invention, the following general methods, and other methods known to one skilled in the art, can be applied to all compounds and subclasses and species of each of these compounds, as described herein. Example 1: (3S,4R)-1-(4-{3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl}benzenesulfonyl)-4- ({4-[(trifluoromethyl)sulfanyl]phenyl}Amino)piperidin-3-ol. i) Under a nitrogen atmosphere, tert-butyl (3S,4R)-4-Amino-3-hydroxypiperidine-1- carboxylate (300 mg), 1-bromo-4-[(trifluoromethyl)sulfanyl]benzene (355 mg) and NaOtBu (185 mg) were added to a solution of Pd(OAc)2(34 mg) and Josiphos SL J009-1 (78 mg) in THF (10 mL). The reaction mixture was stirred overnight at 100 °C and after cooling to room temperature, the reaction mixture was poured into water and the product was extracted into CH2Cl2. The combined organic layers were dried over a phase separation filterand concentrated under reduced pressure. The obtained orange solid was purified on SiO 2,using 4% CH3OH in CH2Cl2 as the eluent, to give tert-butyl (3S,4R)-3-hydroxy-4-({4- [(trifluoromethyl)sulfanyl]phenyl}Amino)piperidine-1-carboxylate (155 mg) as a white solid. ii) To a solution of the product obtained in the previous step (142 mg) in ethyl acetate (2 mL), was added at 0 °C, a 5N HCl solution in 2-propanol (1.5 mL). The reaction mixture was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure giving (3S,4R)-4-({4-[(trifluoromethyl)sulfanyl]phenyl}Amino)piperidin- 3-ol dihydrochloride (131 mg) as an off-white solid, which was used in the next step without further purification.iii) To a solution of the product obtained in the previous step (131 mg) and Et 3N (150 uL) inCH2Cl2 (4 mL) was added 4-bromobenzenesulfonyl chloride (94 mg). The reaction mixture was stirred overnight at room temperature. The reaction mixture was quenched by pouring it into water. The product was extracted into CH2Cl2and the combined organic layers were dried over a phase separation filter and concentrated under vacuo. The obtained yellow solid was purified on SiO2, using 0% to 100% ethyl acetate in heptane as the eluent, to give ((3S,4R)-1-(4-bromobenzenesulfonyl)-4-({4- mg) as a white solid. a was to a suspension of the product obtained in the previous step (193 mg), Bis(pinacolato)diboron (149 mg) and KOAc (118 mg) in 1,4-dioxane (5 mL). The reaction mixture was stirred overnight at 100 °C and after cooling to room temperature the reaction mixture was poured into water. The product was extracted into CH2Cl2, the combined organic layers were dried over a phase separation filter and concentrated under reduced pressure to give (3S,4R)-1-[4-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)benzenesulfonyl]-4-({4- [(trifluoromethyl)sulfanyl]phenyl}Amino)piperidin-3-ol as a black oil, which was used in the next step without further purification. v) To a solution of the product obtained in the previous step (115 mg), 6-bromo-3-methyl- [1,2,4]triazolo[4,3-a]pyridine (46 mg) and NaHCO3 (87 mg) in a dioxane / water (4 / 1) mixture (5 mL), purged with N2 gas, was added Pd(PPh3)4 (13 mg). The reaction mixture was heated overnight at 100 °C in a microwave. After cooling to room temperature, the product was poured into an 1N aqueous NaOH solution. The product was extracted into CH2Cl2, the combined organic layers were dried over a phase separation filter and concentrated under reduced pressure. The residue was purified on C18, using 20% to 95% CH3CN in water as the eluent, giving the title compound (3S,4R)-1-(4-{3-methyl- [1,2,4]triazolo[4,3-a]pyridin-6-yl}benzenesulfonyl)-4-({4- 3-ol (66 mg) as a white solid. MS(ES+) m / z 564.3 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.80 – 8.74 (t, J = 1.4 Hz, 1H), 8.14 – 8.06 (m, 2H), 7.92 – 7.83 (m, 3H), 7.82 – 7.74 (dd, J = 9.6, 1.7 Hz, 1H), 7.33 – 7.26 (d, J = 8.7 Hz, 2H), 6.75 – 6.67 (m, 2H), 6.07 – 6.01 (d, J = 8.3 Hz, 1H), 5.23 – 5.17 (d, J = 4.7 Hz, 1H), 3.90 – 3.83 (s, 1H), 3.62 – 3.49 (m, 2H), 3.49 – 3.38 (m, 1H), 2.81 – 2.75 (s, 3H), 2.75 – 2.67 (m, 1H), 2.65 – 2.55 (m, 1H), 1.88 – 1.78 (m, 1H), 1.70 – 1.63 (m, 1H). Following a procedure analogous to that described for Example 1, using in step i the appropriate (hetero)aryl halide and in step v the appropriate aryl halide, Examples 2 – 5 have been prepared. Example 2: (3S,4R)-1-{4-[3-(propan-2-yl)imidazo[1,2-a]pyridin-6-yl]benzenesulfonyl}-4- ({4-[(trifluoromethyl)sulfanyl]phenyl}Amino)piperidin-3-ol. MS(ES+) m / z 591.3 (M+H)+Building block: Step i: 1-bromo-4-[(trifluoromethyl)sulfanyl]benzene; Step v: 6-bromo-3- (propan-2-yl)imidazo[1,2-a]pyridine.1H NMR (400 MHz, DMSO) δ 8.73 – 8.68 (t, J = 1.4 Hz, 1H), 8.13 – 8.04 (m, 2H), 7.92 – 7.82 (m, 2H), 7.72 – 7.67 (dd, J = 9.4, 0.9 Hz, 1H), 7.66 – 7.60 (dd, J = 9.4, 1.8 Hz, 1H), 7.49 – 7.44 (d, J = 0.7 Hz, 1H), 7.34 – 7.26 (m, 2H), 6.76 – 6.67 (m, 2H), 6.08 – 6.01 (d, J= 8.4 Hz, 1H), 5.23 – 5.17 (d, J = 4.7 Hz, 1H), 3.91 – 3.83 (m, 1H), 3.61 – 3.48 (m, 3H), 3.48 – 3.39 (m, 1H), 2.75 – 2.68 (m, 1H), 2.65 – 2.56 (m, 1H), 1.90 – 1.78 (m, 1H), 1.71 – 1.63 (m, 1H), 1.40 – 1.37 (s, 3H), 1.37 – 1.33 (s, 3H). Example 3: (3S,4R)-1-(4-{3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl}benzenesulfonyl)-4- ({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol. MS(ES+) m / z 565.3 (M+H)+Building blocks: Step i: 2-chloro-5-[(trifluoromethyl)sulfanyl]pyridine; Step v: 6-bromo- 3-methyl-[1,2,4]triazolo[4,3-a]pyridine.1H NMR (400 MHz, DMSO) δ 8.80 – 8.75 (t, J = 1.4 Hz, 1H), 8.14 – 8.11 (d, J = 2.5 Hz, 1H), 8.11 – 8.05 (m, 2H), 7.91 – 7.84 (m, 3H), 7.81 – 7.74 (dd, J = 9.6, 1.7 Hz, 1H), 7.60 – 7.53 (dd, J = 8.8, 2.5 Hz, 1H), 7.15 – 7.09 (d, J = 7.4 Hz, 1H), 6.72 – 6.65 (dd, J = 8.8, 0.7 Hz, 1H), 5.28 – 5.22 (d, J = 4.7 Hz, 1H), 3.92 – 3.87 (m, 2H), 3.59 – 3.47 (m, 2H), 2.81 – 2.76 (s, 3H), 2.75 – 2.68 (m, 1H), 2.67 – 2.56 (m, 1H), 1.96 – 1.84 (m, 1H), 1.71 – 1.63 (m, 1H). Example 3: (3S,4R)-1-(4-{3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6- yl}benzenesulfonyl)-4-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}amino)piperidin-3-ol. i) Under a nitrogen atmosphere, tert-butyl (3S,4R)-4-amino-3-hydroxypiperidine-1- carboxylate (303 mg), 2-chloro-5-[(trifluoromethyl)sulfanyl]pyridine (295 mg) and NaOtBu (186 mg) were added to a solution of Pd(OAc)2 (40 mg) and Josiphos SL J009-1 (80 mg) in THF (10 mL). The reaction mixture was stirred overnight at 100 °C and after cooling to room temperature, the reaction mixture was poured into water (100 mL) and the product was extracted into CH2Cl2 (3 * 50 mL). The combined organic layers were dried over MgSO4, and concentrated under reduced pressure. The obtained black oil was purified on SiO2, using 0% to 10% CH3OH in CH2Cl2as the eluent, to give tert-butyl (3S,4R)-3- hydroxy-4-({5-[ 2- piperidine-1-carboxylate (142 mg) as a white solid. ii) To a solution of the product obtained in the previous step (140 mg) in ethyl acetate (2 mL), was added at 0 ^C, a 5N HCl solution in 2-propanol (1.6 mL). The reaction mixture was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure giving (3S,4R)-4-({5-[(trifluoromethyl)sulfanyl]pyridin-2- 3-ol dihydrochloride (163 mg) as a white solid, which was used in the next step without further purification. iii) To a solution of the product obtained in the previous step (163 mg) and Et 3N(170 uL) in CH2Cl2(4 mL) was added 4-bromobenzenesulfonyl chloride (114 mg). The reaction mixture was for 2 hours at room temperature. The reaction mixture was quenched by pouring it into water (50 mL). The product was extracted into CH2Cl2 (3 * 25 mL), the combined organic layers were dried over a phase separation filter and concentrated under reduced pressure giving (3S,4R)-1-(4-bromobenzenesulfonyl)-4-({5- pyridin-2-yl}amino)piperidin-3-ol (212 mg) as an off-white solid, was next step without further purification iv) Under a nitrogen atmosphere, Pd(dppf)Cl2 (17 mg) was added to a suspension of the product obtained in the previous step (212 mg), Bis(pinacolato)diboron (161 mg) and KOAc (125 mg) in 1,4-dioxane (5 mL). The reaction mixture was stirred overnight at 100 ^C and after cooling to room temperature the reaction mixture was poured into water (30 mL). The product was extracted into CH2Cl2(3 * 15 mL), the combined organic layers were dried over a phase separation filter and concentrated under reduced pressure to give (3S,4R)-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonyl]-4-({5- 3-ol as a black oil, which was used next step v) To a solution of the product obtained in the previous step (105 mg), 6-bromo-3- methyl-[1,2,4]triazolo[4,3-a]pyridine (42 mg) and NaHCO3 (79 mg) in a dioxane / water (4 / 1) mixture (5 mL), purged with N2gas, was added Pd(PPh3)4(12 mg). The reaction mixture was heated overnight at 100 ^C in a microwave. After cooling to room temperature, the product was poured into an 1N aqueous NaOH solution (25 mL). The product was extracted into CH2Cl2 (3 * 20 mL), the combined organic layers were dried over a phase separation filter and concentrated under reduced pressure. The residue was purified on C18, using 20% to 95% CH3CN in water as the eluent, giving the title compound (3S,4R)-1-(4- {3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl}benzenesulfonyl)-4-({5- 3-ol (45 mg) as a white solid. MS(ES+) m / z 565.3 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.80 – 8.75 (t, J = 1.4 Hz, 1H), 8.14 – 8.11 (d, J = 2.5 Hz, 1H), 8.11 – 8.05 (m, 2H), 7.91 – 7.84 (m, 3H), 7.81 – 7.74 (dd, J = 9.6, 1.7 Hz, 1H), 7.60 – 7.53 (dd, J = 8.8, 2.5 Hz, 1H), 7.15 – 7.09 (d, J = 7.4 Hz, 1H), 6.72 – 6.65 (dd, J = 8.8, 0.7 Hz, 1H), 5.28 – 5.22 (d, J = 4.7 Hz, 1H), 3.92 – 3.87 (m, 2H), 3.59 – 3.47 (m, 2H), 2.81 – 2.76 (s, 3H), 2.75 – 2.68 (m, 1H), 2.67 – 2.56 (m, 1H), 1.96 – 1.84 (m, 1H), 1.71 – 1.63 (m, 1H). Example 4: (3S,4R)-1-{4-[3-(propan-2-yl)imidazo[1,2-a]pyridin-6-yl]benzenesulfonyl}-4- ({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol. MS(ES+) m / z 592.3 (M+H)+Building blocks: Step i: 2-chloro-5-[(trifluoromethyl)sulfanyl]pyridine; Step v: 6-bromo- 3-(propan-2-yl)imidazo[1,2-a]pyridine.1H NMR (400 MHz, DMSO) δ 8.73 – 8.68 (t, J = 1.4 Hz, 1H), 8.13 – 8.04 (m, 2H), 7.92 – 7.82 (m, 2H), 7.72 – 7.67 (dd, J = 9.4, 0.9 Hz, 1H), 7.66 – 7.60 (dd, J = 9.4, 1.8 Hz, 1H), 7.49 – 7.44 (d, J = 0.7 Hz, 1H), 7.34 – 7.26 (m, 2H), 6.76 – 6.67 (m, 2H), 6.08 – 6.01 (d, J= 8.4 Hz, 1H), 5.23 – 5.17 (d, J = 4.7 Hz, 1H), 3.91 – 3.83 (m, 1H), 3.61 – 3.48 (m, 3H), 3.48 – 3.39 (m, 1H), 2.75 – 2.68 (m, 1H), 2.65 – 2.56 (m, 1H), 1.90 – 1.78 (m, 1H), 1.71 – 1.63 (m, 1H), 1.40 – 1.37 (s, 3H), 1.37 – 1.33 (s, 3H). Example 5: (3S,4R)-1-{4-[3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyrazin-6- yl]benzenesulfonyl}-4-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol. MS(ES+) m / z 594.1 (M+H)+Building blocks: Step i: 2-chloro-5-[(trifluoromethyl)sulfanyl]pyridine; Step v: 6-chloro- 3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyrazine.1H NMR (400 MHz, DMSO) δ 8.73 – 8.68 (t, J = 1.4 Hz, 1H), 8.13 – 8.04 (m, 2H), 7.92 – 7.82 (m, 2H), 7.72 – 7.67 (dd, J = 9.4, 0.9 Hz, 1H), 7.66 – 7.60 (dd, J = 9.4, 1.8 Hz, 1H), 7.49 – 7.44 (d, J = 0.7 Hz, 1H), 7.34 – 7.26 (m, 2H), 6.76 – 6.67 (m, 2H), 6.08 – 6.01 (d, J= 8.4 Hz, 1H), 5.23 – 5.17 (d, J = 4.7 Hz, 1H), 3.91 – 3.83 (m, 1H), 3.61 – 3.48 (m, 3H), 3.48 – 3.39 (m, 1H), 2.75 – 2.68 (m, 1H), 2.65 – 2.56 (m, 1H), 1.90 – 1.78 (m, 1H), 1.71 – 1.63 (m, 1H), 1.40 – 1.37 (s, 3H), 1.37 – 1.33 (s, 3H). Example 6: (3S,4R)-1-{4-[3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6- yl]benzenesulfonyl}-4-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol. i) To a solution of ((3S,4R)-1-(4-bromobenzenesulfonyl)-4-({4- [(trifluoromethyl)sulfanyl]phenyl}Amino)piperidin-3-ol (example 1, step iii, 80 mg), 3- (propan-2-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,2,4]triazolo[4,3-a]pyridine (129 mg) and K2CO3 (40 mg) in a dioxane / water (4 / 1) mixture (2.5 mL), purged with N2 gas, was added Pd(dppf)Cl2(11 mg). The reaction mixture was heated overnight at 90 °C. After cooling to room temperature, the reaction mixture was filtered and concentrated under reduced pressure. The residue was purified on C18, using 45% to 75% CH3CN in water as the eluent, giving the title compound (3S,4R)-1-{4-[3-(propan-2- triazolo[4,3- a]pyridin-6-yl]benzenesulfonyl}-4-({5-[(trifluoromethyl)sulfanyl] yl}Amino)piperidin-3-ol (21 mg) as a white solid. MS(ES+) m / z 593.2 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.82 (s, 1H), 8.49 (d, J = 2.4 Hz, 1H), 8.04 - 8.01 (m, 3H), 7.88 - 7.85 (m, 1H), 7.83 (d, J = 8.4 Hz, 2H), 7.81 - 7.75 (m, 1H), 7.72 – 7.58 (m, 1H)， 7.02 - 6.98 (m, 1H), 5.13 (d, J = 2.4 Hz, 1H), 3.78 - 3.69 (m, 2H), 3.54 - 3.51 (m, 2H), 3.04 (dd, J = 3.6, 8.4 Hz, 1H), 2.97 (d, J = 11.2 Hz, 1H), 2.79 - 2.69 (m, 1H), 1.78 - 1.76 (m, 2H), 1.42 (d, J = 6.8 Hz, 6H). Following a procedure analogous to that described for Example 6, using in step i the appropriate boronic acid or boronic ester, Examples 7 – 8 have been prepared. Example 7: (3S,4R)-1-{4-[8-methyl-3-(propan-2-yl)imidazo[1,2-a]pyridin-6- yl]benzenesulfonyl}-4-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol.

[0006] MS(ES+) m / z 606.2 (M+H)+Building block: Step i: 8-methyl-3-(propan-2-yl)-6-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)imidazo[1,2-a]pyridine.1H NMR (400 MHz, DMSO) δ 8.43 (d, J=2.4 Hz, 1H), 8.40 (s, 1H), 7.98 (dd, J = 2.4, 8.8 Hz, 1H), 7.92 - 7.87 (m, 2H), 7.86 - 7.81 (m, 2H), 7.47 - 7.41 (m, 2H), 7.01 (d, J = 8.4 Hz, 1H), 5.36 (s, 1H), 4.26 (d, J = 13.6 Hz, 1H), 3.96 (d, J = 12.0 Hz, 1H), 3.45 - 3.38 (m, 1H), 3.36 (s, 1H), 2.89 (d, J = 13.6 Hz, 1H), 2.81 - 2.71 (m, 1H), 2.64 (s, 3H), 2.22 - 2.09 (m, 1H), 1.97 (d, J = 12.8 Hz, 1H), 1.44 (d, J = 6.8 Hz, 6H). Example 8: (3S,4R)-1-{4-[3-(difluoromethyl)-[1,2,4]triazolo[4,3-a]pyridin-6- yl]benzenesulfonyl}-4-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol. MS(ES+) m / z 601.1 (M+H)+Building block: Step i: 3-(difluoromethyl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)- [1,2,4]triazolo[4,3-a]pyridine. 1H NMR (400 MHz, DMSO) δ 8.38 (d, J = 2.4 Hz, 1H), 8.01 (d, J = 9.6 Hz, 1H), 7.90 (d, J = 8.4 Hz, 2H), 7.85 (dd, J = 2.4, 8.4 Hz, 1H), 7.72 (d, J = 8.4 Hz, 2H), 7.67 (dd, J = 1.2, 9.6 Hz, 1H), 7.31 (t, J = 52 Hz, 1H), 6.85 (d, J = 8.8 Hz, 1H), 5.39 - 5.28 (m, 1H), 3.90 (dd, J = 4.8, 12.0 Hz, 1H), 3.71 - 3.60 (m, 1H), 3.20 - 3.13 (m, 1H), 3.06 (dd, J = 2.0, 12.4 Hz, 1H), 2.93 - 2.85 (m, 1H), 2.00 - 1.88 (m, 2H). Example 9: 8-(4-{[(3S,4R)-3-hydroxy-4-({5-[(trifluoromethyl)sulfanyl]pyridin-2- yl}Amino)piperidin-1-yl]sulfonyl}phenyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione. i) To a solution of (3S,4R)-4-((5-((trifluoromethyl)thio)pyridin-2-yl)Amino)piperidin-3-ol hydrochloride (example 1, step ii, 300.0 mg), DMAP (11.11 mg) and TEA (0.63 mL) in DCM (10 mL) was added, under a nitrogen atmosphere, 4-fluorobenzenesulfonyl chloride (159.33 mg) at 0 °C and stirred at 25 °C for 2 hours. A saturated NaHCO3 aqueous solution (30 mL) was added, and the product was extracted into CH2Cl2. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give (3S,4R)-1-(4-fluorobenzenesulfonyl)-4-({5- [(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol (360.0 mg) as yellow solid,which was used in the next step without further purification.ii) To a solution of of the product obtained in the previous step (120.0 mg) and 1,3,8- triazaspiro[4.5]decane-2,4-dione (134.9 mg) and in DMSO (2 mL) was added K2CO3 (183.3 mg). The reaction mixture was stirred at 120 °C for 14 hours and after cooling to room temperature the reaction mixture was filtered. The residue was purified on C18, using 35% to 65% CH3CN in water as the eluent, giving the title compound 8-(4-{[(3S,4R)-3-hydroxy- 4-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-1-yl]sulfonyl}phenyl)-1,3,8- triazaspiro[4.5]decane-2,4-dione (24.4 mg) as a white solid. MS(ES+) m / z 601.1 (M+H)+.1H NMR (400 MHz, DMSO) δ 10.68 (br s, 1H), 8.56 (s, 1H), 8.12 (d, J = 2.4 Hz, 1H), 7.56 (dd, J = 2.4, 8.8 Hz, 1H), 7.52 (d, J = 9.2 Hz, 2H), 7.10 (d, J = 9.2 Hz, 3H), 6.69 (d, J = 8.8 Hz, 1H), 5.17 (d, J = 4.4 Hz, 1H), 3.85 (dd, J = 4.8, 8.0 Hz, 4H), 3.45 - 3.35 (m, 2H), 3.29 - 3.21 (m, 2H), 2.58 (d, J = 12.0 Hz, 1H), 2.45 (s, 1H), 1.93 - 1.80 (m, 3H), 1.65 (d, J = 13.2 Hz, 3H) Following a procedure analogous to that described for Example 9, using in step ii the appropriate amine, Examples 10 – 11 have been prepared. Example 10: (3S,4R)-1-(4-{2-methoxy-7-azaspiro[3.5]nonan-7-yl}benzenesulfonyl)-4-({5- [(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol. MS(ES+) m / z 587.2 (M+H)+Building block: Step ii: 2-methoxy-7-azaspiro[3.5]nonane hydrochloride.1H NMR (400 MHz, DMSO) δ 8.11 (d, J = 2.4 Hz, 1H), 7.55 (dd, J = 2.4, 8.8 Hz, 1H), 7.48 (d, J = 8.8 Hz, 2H), 7.05 (d, J = 9.2 Hz, 3H), 6.68 (d, J = 8.8 Hz, 1H), 5.16 (s, 1H), 3.92 - 3.86 (m, 1H), 3.85 (s, 2H), 3.43 - 3.34 (m, 4H), 3.28 - 3.24 (m, 2H), 3.12 (s, 3H), 2.57 - 2.53 (m, 1H), 2.48 - 2.40 (m, 1H), 2.21 - 2.12 (m, 2H), 1.92 - 1.81 (m, 1H), 1.67 - 1.61 (m, 3H), 1.59 (dd, J = 4.0, 7.2 Hz, 4H). Example 11: 8-(4-{[(3S,4R)-3-hydroxy-4-({5-[(trifluoromethyl)sulfanyl]pyridin-2- yl}Amino)piperidin-1-yl]sulfonyl}phenyl)-2,8-diazaspiro[4.5]decan-1-one. MS(ES+) m / z 586.2 (M+H)+Building block: Step ii: 2,8-diazaspiro[4.5]decan-1-one hydrochloride.1H NMR (400 MHz, DMSO) δ 8.12 (d, J = 2.4 Hz, 1H), 7.61 (s, 1H), 7.56 (dd, J = 2.0, 8.8 Hz, 1H), 7.51 (d, J = 9.2 Hz, 2H), 7.07 (d, J = 9.2 Hz, 3H), 6.69 (d, J = 8.8 Hz, 1H), 5.17 (d, J = 4.4 Hz, 1H), 3.85 (dd, J = 4.0, 8.4 Hz, 4H), 3.44 - 3.34 (m, 2H), 3.20 (t, J = 6.8 Hz, 2H), 3.09 - 2.98 (m, 2H), 2.58 (d, J = 11.2 Hz, 1H), 2.49 - 2.42 (m, 1H), 2.03 (t, J = 6.8 Hz, 2H), 1.93 - 1.81 (m, 1H), 1.78 - 1.68 (m, 2H), 1.64 (dd, J = 4.4, 9.2 Hz, 1H), 1.44 (d, J = 13.2 Hz, 2H). Example 12: (1R,2R,5R)-5-{4-[3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6- yl]benzenesulfonyl}-2-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)cyclohexan-1-ol. i) To an ice cold solution of (2R)-2-{[(tert-butoxy)carbonyl]Amino}hex-5-enoic acid (4.50 g) and DIPEA (13.7 mL) in DMF (130 mL) were added methoxy(methyl)amine hydrochloride (1.96 g) and HATU (9.00 g). The reaction mixture was stirred for 30 minutes at 0 °C and a further 75 minutes at room temperature. After completion water was added and the product was extracted into ethyl acetate. The combined organic layers were washed with water, brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude yellow oil was purified on SiO2, using 0% to 40% ethyl acetate in heptane as the eluent, to give tert-butyl N- -1-[methoxy(methyl)carbamoyl]pent-4-en-1-yl]carbamate (5.08 g) as a colorless oil, solidified over time. ii) Under a nitrogen atmosphere, a 0.7 N vinyl magnesium bromide solution in dry THF (115 mL) was added to an ice cold solution of the product obtained in the previous step(5.08 g) in 100 mL THF. The reaction mixture was stirred for 3 hours at 0 °C to roomtemperature. The reaction mixture was quenched by pouring it into a cold aqueous 1N HCl solution (150 mL) and the product was extracted into ethyl acetate. The organic layer was washed with an aqueous 1N HCl solution, water, brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude brown oil was purified on SiO2, using 0% to 20% ethyl acetate in heptane as the eluent, to give tert-butyl N-[(4R)-3-oxoocta-1,7-dien- 4-yl]carbamate (2.88 g) as a yellow liquid. iii) Under a nitrogen atmosphere, Grubbs Catalyst, 2nd Generation (461 mg), was added to a solution of the product obtained in the previous step (2.88 g) in dry CH 2Cl2 (75 mL). Thereaction mixture was stirred at room temperarure for 3.5 hours and the mixture was concentrated under reduced pressure. The residue was purified on SiO2, using 0% to 30% ethyl acetate in heptane as the eluent, to give tert-butyl N-[(1R)-2-oxocyclohex-3-en-1- yl]carbamate (2.25 g) as a brown oil. iv) Under a nitrogen atmosphere, 4-bromothiophenol (6.09 g), was added to a solution of the product obtained in the previous step (2.25 g) and Et3N (7.30 mL) in dry CH2Cl2 (50 mL). The reaction mixture was stirred at room temperature for 3 hours and the mixture was concentrated under reduced pressure. The residue was purified on SiO2, using 0% to 30% ethyl acetate in heptane as the eluent, to give tert-butyl N-[(1R,4R)-4-[(4- tert-butyl N-[(1R,4S)-4- . a trans tert- - bromophenyl)sulfanyl]-2- obtained in the previous step (1.08 g) in dry methanol (25 mL), was added NaBH4(115 mg) at -78 °C. The reaction mixture was stirred for 2.5 hours at 0 °C, and after completion the reaction mixture was quenched by pouring it into a saturated aqueous NHCl4 solution. The product was extracted into CH2Cl2. The combined organic layers were dried over a phase separation filter and concentrated under reduced pressure. The residue was purified on SiO2, using 0% to 30% ethyl acetate in heptane as the eluent, to give tert-butyl N-[(1R,2R,4R)-4-[(4-bromophenyl)sulfanyl]-2- -4-[(4- mg). vi) To a solution of tert-butyl N-[(1R,2R,4R)-4-[(4-bromophenyl)sulfanyl]-2- mg) in CH2Cl2 (8 mL) was added at 0 °C, mCPBA (436 mg) and the reaction mixture was stirred for 15 minutes at room temperature. The reaction mixture was quenched by adding an aqueous 1N NaOH solution (30 mL). The product was extracted into CH2Cl2. The combined organic layers were dried over a phase separation filter and concentrated under reduced pressure. The residue was purified on SiO2, using 0% to 50% ethyl acetate in heptane as the eluent, to give tert-butyl N-[(1R,2R,4R)-4-(4- bromobenzenesulfonyl)-2- (295 mg) as a white solid. vii) Under a nitrogen atmosphere, Pd(PPh3)4 (39 mg) was added to a suspension of the product obtained in the previous step (295 mg), [3-(propan-2-yl)-[1,2,4]triazolo[4,3- a]pyridin-6-yl]boronic acid (151 mg) and NaHCO3(283 mg) in a dioxane / water (4 / 1) mixture (5 mL). The reaction mixture was stirred for 1 hour at 100 °C under a nitrogen atmosphere. After cooling to room temperature, water was added, and the product was extracted into ethyl acetate. The combined organic layers were washed with water, brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified on SiO2, using 0% to 10% methanol in CH2Cl2 as the eluent, to give tert-butyl N-[(1R,2R,4R)-2-hydroxy-4-{4-[3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6- yl]benzenesulfonyl}cyclohexyl]carbamate (307 mg) as an off white solid. viii) A solution of the product obtained in the previous step (307 mg) in trifluoroacetic acid (2 mL) was stirred for 1 hour at 65 °C and after completion the mixture was concentrated under reduced pressure to give (1R,2R,5R)-2-Amino-5-{4-[3-(propan-2-yl)- [1,2,4]triazolo[4,3-a]pyridin-6-yl]benzenesulfonyl}cyclohexan-1-ol; bis(trifluoroacetic acid) (381 mg) as a yellow solid, which was used in the next step without further purification. ix) To a solution of the product obtained in the previous step (127 mg) in DMSO (1.5 mL) were added DIPEA (105 uL), KF (68 mg) and 2-chloro-5- [(trifluoromethyl)sulfanyl]pyridine (54 mg). The reaction mixture was stirred for 40 hours at 100 °C, in a microwave, under a nitrogen atmosphere. After cooling to room temperature, the mixture was poured into water and the product was extracted into CH2Cl2. The combined organic layers were dried over a phase separation filter and concentrated under reduced pressure. The crude product was purified on SiO2, using 0% to 10% methanol in CH2Cl2as the eluent, to give the title product (1R,2R,5R)-5-{4-[3-(propan-2-yl)- [1,2,4]triazolo[4,3-a]pyridin-6-yl]benzenesulfonyl}-2-({5- [(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)cyclohexan-1-ol (56 mg) as a white solid. MS(ES+) m / z 592.3 (M+H)+.1H NMR (400 MHz, DMSO) δ 8.88 (t, J = 1.4 Hz, 1H), 8.13 (dd, J = 8.3, 2.1 Hz, 3H), 8.03 – 7.95 (m, 2H), 7.88 (dd, J = 9.6, 1.0 Hz, 1H), 7.79 (dd, J = 9.6, 1.6 Hz, 1H), 7.56 (dd, J = 8.9, 2.5 Hz, 1H), 7.21 (d, J = 7.5 Hz, 1H), 6.59 (d, J = 8.9 Hz, 1H), 4.99 (d, J = 5.6 Hz, 1H), 3.74 (p, J = 6.8 Hz, 1H), 3.61 – 3.49 (m, 1H), 3.43 (tt, J = 10.2, 5.0 Hz, 1H), 2.15 (d, J = 12.0 Hz, 1H), 2.08 – 2.01 (m, 1H), 1.93 (d, J = 12.6 Hz, 1H), 1.43 (d, J = 6.8 Hz, 6H), 1.42 – 1.33 (m, 2H), 1.31 – 1.13 (m, 1H). Following a procedure analogous to that described for Example 12, proceeding in step vi with the desired stereoisomer, and using in step vii the appropriate boronic esters or boronic acids, Examples 13 - 16 have been prepared. Example 13: (1R,2R,5R)-5-(4-{3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6- yl}benzenesulfonyl)-2-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)cyclohexan-1-ol. MS(ES+) m / z 564.3 (M+H)+Building block: Step vii: {3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl}boronic acid.1H NMR (400 MHz, DMSO) δ 8.81 (t, J = 1.4 Hz, 1H), 8.17 – 8.10 (m, 3H), 8.03 – 7.96 (m, 2H), 7.87 (dd, J = 9.6, 1.1 Hz, 1H), 7.79 (dd, J = 9.6, 1.7 Hz, 1H), 7.56 (dd, J = 8.9, 2.5 Hz,1H), 7.21 (d, J = 7.4 Hz, 1H), 6.59 (dd, J = 8.8, 0.7 Hz, 1H), 4.99 (d, J = 5.6 Hz, 1H), 3.62 –3.48 (m, 2H), 3.43 (tt, J = 10.2, 5.2 Hz, 1H), 2.78 (s, 3H), 2.15 (d, J = 12.1 Hz, 1H), 2.05 (dd, J = 13.1, 3.8 Hz, 1H), 1.93 (d, J = 12.6 Hz, 1H), 1.50 – 1.32 (m, 2H), 1.21 (q, J = 11.4 Hz, 1H). Example 14: (1R,2R,5R)-5-(4-{imidazo[1,2-a]pyridin-6-yl}benzenesulfonyl)-2-({5- [(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)cyclohexan-1-ol. MS(ES+) m / z 549.3 (M+H)+Building block: Step vii: 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2- a]pyridine.1H NMR (400 MHz, DMSO) δ 9.12 (dd, J = 1.8, 1.1 Hz, 1H), 8.14 (d, J = 2.4 Hz, 1H), 8.08 – 8.02 (m, 2H), 8.01 (dd, J = 1.3, 0.7 Hz, 1H), 8.00 – 7.95 (m, 2H), 7.75 – 7.64 (m, 3H), 7.56 (dd, J = 8.9, 2.5 Hz, 1H), 7.21 (d, J = 7.5 Hz, 1H), 6.59 (d, J = 8.9 Hz, 1H), 4.98 (d, J = 5.6 Hz, 1H), 3.64 – 3.50 (m, 2H), 3.44 (ddt, J = 15.2, 10.2, 4.7 Hz, 1H), 2.15 (d, J = 12.1 Hz, 1H), 2.06 (dt, J = 13.3, 2.7 Hz, 1H), 1.93 (d, J = 12.5 Hz, 1H), 1.51 – 1.31 (m, 2H), 1.21 (q, J = 10.6 Hz, 1H). Example 15: (1R,2R,5R)-5-{4-[8-methyl-3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6- yl]benzenesulfonyl}-2-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)cyclohexan-1-ol. MS(ES+) m / z 606.3 (M+H)+Building block: Step vii: [8-methyl-3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6- yl]boronic acid.1H NMR (400 MHz, DMSO) δ 8.74 (t, J = 1.2 Hz, 1H), 8.16 – 8.07 (m, 3H), 8.01 – 7.95 (m, 2H), 7.62 (t, J = 1.5 Hz, 1H), 7.56 (dd, J = 8.9, 2.5 Hz, 1H), 7.21 (d, J = 7.4 Hz, 1H), 6.59(d, J = 8.9 Hz, 1H), 4.99 (d, J = 5.6 Hz, 1H), 3.71 (hept, J = 6.8 Hz, 1H), 3.52 (dd, J = 14.2,11.0 Hz, 2H), 3.43 (tt, J = 10.2, 5.0 Hz, 1H), 2.60 (d, J = 1.1 Hz, 3H), 2.20 – 2.11 (m, 1H), 2.10 – 2.02 (m, 1H), 1.98 – 1.88 (m, 1H), 1.43 (d, J = 6.8 Hz, 6H), 1.40 – 1.32 (m, 2H), 1.28 – 1.13 (m, 1H). Example 16: (1S,2R,5R)-5-{4-[3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6- yl]benzenesulfonyl}-2-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)cyclohexan-1-ol. MS(ES+) m / z 592.3 (M+H)+ Building block: Step vii: [3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]boronic acid.1H NMR (400 MHz, DMSO) δ 8.87 (t, J = 1.4 Hz, 1H), 8.15 (d, J = 2.4 Hz, 1H), 8.14 – 8.10 (m, 2H), 8.01 – 7.95 (m, 2H), 7.88 (dd, J = 9.6, 1.0 Hz, 1H), 7.78 (dd, J = 9.6, 1.7 Hz, 1H), 7.57 (dd, J = 8.8, 2.5 Hz, 1H), 7.06 (s, 1H), 6.66 (dd, J = 8.8, 0.7 Hz, 1H), 5.10 (d, J = 4.3 Hz, 1H), 4.03 (s, 1H), 3.81 (s, 1H), 3.74 (p, J = 6.9 Hz, 1H), 3.50 – 3.39 (m, 1H), 2.08 –1.96 (m, 2H), 1.77 – 1.57 (m, 3H), 1.50 (td, J = 12.3, 4.2 Hz, 1H), 1.43 (d, J = 6.8 Hz, 6H).HUMAN CCR6-CRE REPORTER ASSAY 293FT cells were transfected with 2 constructs using TransIT-293 (Mirus). The first construct (pGL4.29, Promega) expressed the luciferase reporter gene luc2P in response to the binding of cAMP-induced CREB to the CREelement in its promoter. The second construct contained the open reading frame of human CCR6 in the pUNO1 backbone under the control of an enhanced CMV promoter (InVivoGen).48h after transfection, cells were harvested and diluted to 750,000 cells / ml in culture medium (DMEM, 10% FBS, 1x pen / strep (Gibco 15140)). Compounds were 2.5-fold serially diluted in DMSO. Further dilutions were made in assay medium (DMEM, 10% FBS, 1x pen / strep, 6μM Forskolin, 6nM CCL20).4μl of the compound solution was added to a white MW384 plate, followed by 20μl of the cell suspension. Final DMSO concentration in the assay was 0.1%. The MW384 plate was placed in an incubator at 37° C, 5% CO2 for 5h. Luciferase activity was determined by addition of 24 μl of a 2.5x diluted BriteLite luciferase solution (Perkin Elmer), followed by luminescence measurement using a VICTOR Plate reader (Perkin Elmer). To deselect compounds that did not specifically bind CCR6, the assay was also performed with transfected 293FT cells in which CCR6 was replaced with an empty vector using the same backbone. The relative LogIC50 was determined with GraphPad Prism 9 using a four-parameter dose-response model. CHO-K1 CCR6 CHEMOTAXIS ASSAY TOWARDS CCL20 Cells overexpressing human CCR6 were used in the chemotaxis assay (DiscoverX, cAMP Hunter™ CHO-K1 CCR6 Gi Cell Line). Growth medium of these cells consisted of DMEM / F12, non-essential amino acids (1xNEAA, Gibco 11140050), 10% FBS and 1x pen / strep (Gibco 15140). For the chemotaxis assay, Corning Transwell plates were used with a pore size of 8 μm (Corning 351164). Cells were harvested using trypsin and diluted to 4*10^6 cells / ml in chemotaxis medium (DMEM, 0.25% BSA, pen / strep). Compounds were four-fold serially diluted in DMSO. Further dilutions were made in chemotaxis medium. Cells were incubated with test compounds for 30 min at 37° C prior to initiation of the assay (2*10^6 cells / ml). Final DMSO concentration in the assay was 0.2%. Wells of the Transwell plates were filled with 200 μl chemotaxis medium containing 100 ng / ml CCL20 (R&D systems 360-MP).50 μl of the cell / compound suspension was added to the inserts of the Transwell plates (100,000 cells / insert). The Transwell plates were placed in an incubatorat 37° C, 5% CO2 for 4h. After 4h, the number of migrated cells was quanti fied usingCellTiter Glo (Promega). Percentage inhibition values were calculated based on the low and high signal obtained with 0.2% DMSO in chemotaxis medium without and with CCL20, respectively. The relative LogIC50 was determined with GraphPad Prism 9 using a four- parameter dose-response model. CD4+ T CELLS CHEMOTAXIS ASSAY TOWARDS CCL20 Human CD4+ T cells were isolated from buffy coats of healthy donors using a CD4+T Cell Isolation Kit (Miltenyi Biotec 130-096-533). Isolated T cells were stimulated overnight with anti-CD3 and anti-CD28 antibodies (Biolegend 300314 / 302934) in growth medium (RPMI1640, 10% heat-inactivated FBS, 1x pen / strep (Gibco 15140)). For the chemotaxis assay, Corning Transwell plates were used with a pore size of 5 μm (Corning 3388). T cells were counted and diluted to 6*10^6 cells / ml in chemotaxis medium (RPMI1640, 1% BSA, pen / strep). Compounds were four-fold serially diluted in DMSO. Further dilutions were made in chemotaxis medium. Cells were incubated with test compounds for 30 min at 37° C prior to initiation of the assay (3*10^6 cells / ml). Final DMSO concentration in the assay was 0.2%. Wells of the Transwell plates were filled with 200 μl chemotaxis medium containing 150 ng / ml CCL20 (R&D systems 360-MP).50 μl of the cell / compound suspension was added to the inserts of the Transwell plates (150,000 cells / insert). The Transwell plates were placed in an incubator at 37° C, 5% CO2 for 3 h. After 3 h, the number of migrated cells was quantified using CellTiter Glo (Promega). Percentage inhibition values were calculated based on the low and high signal obtained with 0.2% DMSO in chemotaxis medium without and with CCL20, respectively. The relative LogIC50 was determined with GraphPad Prism 9 using a four-parameter dose-response model. The tables below show the data for selected compounds: Table 1: CCR6-CRE reporter assay Example number CCR6-CRE reporter 1 7.5 2 7.5 3 7.7 4 7.7 5 7.9 6 6.8 7 6.8 8 7.2 9 7.9 10 7.3 11 7.5 12 6.5 13 5.5 14 6.5 15 6.9 16 7.4 Table 2: CHO-K1 CCR6 chemotaxis assay Example number CHO-K1 CCR6 chemotaxis 1 8.2 2 8.4 3 8.1 4 8.4 5 8.2 6 7.5 7 7.5 8 7.2 9 8.5 10 7.7 11 8.2 12 6.5 14 6.0 15 6.3 16 8.2 Table 3: CD4+ T cells chemotaxis assay Example number CD4+ T-cell chemotaxis 3 8.8 5 8.7 6 7.9 8 7.8 9 8.6 11 8.4 Aspects 1. A compound of formula (I) wherein X1is CH or N; X2is CH or N; X3is CH or N; X4is O or NH; X5is CH or N; R1is aryl, heterocyclyl, or heteroaryl, wherein aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more R1a; R1ais C1-6alkyl, oxo, cyano, carbamoyl, C1-6haloalkyl, C1-6alkoxy, C1-6alkylcarbamoyl-, C1-6alkoxyC1-6alkyl-, C3‑6cycloalkyl, or heterocyclyl; R2is hydrogen or halogen; R3is hydrogen or halogen; R4is OH; R5is hydrogen or C1-6alkyl; R6is -OR6a, -SR6b, or hydrogen; R6ais C1-6haloalkyl; R6bis C1-6haloalkyl; R7is -OR7a, -SR7b, or hydrogen; R7ais C1-6haloalkyl; R7bis C1-6haloalkyl; provided that R6and R7must be different, and R6or R7is hydrogen, or pharmaceutically acceptable salts thereof. 2. The compound of aspect 1 wherein X1is CH. 3. The compound of aspect 1 wherein X1is N. 4. The compound of any one of aspects 1 to 3 wherein X4is O. 5. The compound of any one of aspects 1 to 4 wherein X5is CH. 6. The compound of any one of aspects 1 to 4 wherein X5is N. 7. The compound of any one of aspects 1 to 6, or a pharmaceutically acceptable salt thereof, wherein X1is N, X2is CH, X3is CH, X4is O, and X5is CH. 8. The compound of any one of aspects 1 to 7, or a pharmaceutically acceptable salt thereof, wherein X1is N, X2is CH, X3is CH, X4is O, and X5is N. 9. The compound of any one of aspects 1 to 8, or a pharmaceutically acceptable salt thereof, wherein R1is heterocyclyl, or heteroaryl, wherein heterocyclyl, and heteroaryl, are optionally substituted with one or more R1a. 10. The compound of any one of aspects 1 to 9 or a pharmaceutically acceptable salt thereof, wherein R1is triazolopyrazinyl, triazolopyridinyl, imidazopyridinyl, triazaspirodecanyl, diazaspirodecanyl, or azaspirononanyl, wherein triazolopyrazinyl, triazolopyridinyl, imidazopyridinyl, triazaspirodecanyl, diazaspirodecanyl, and azaspirononanyl are optionally substituted with one or more R1a. 11. The compound of any one of aspects 1 to 9 or a pharmaceutically acceptable salt thereof, wherein R1is triazolopyrazinyl, triazolopyridinyl, imidazopyridinyl, diazaspirodecanyl, or azaspirononanyl, wherein triazolopyrazinyl, triazolopyridinyl, imidazopyridinyl, diazaspirodecanyl, and azaspirononanyl are optionally substituted with one or more R1a. 12. The compound of any one of aspects 1-10 or a pharmaceutically acceptable salt thereof, wherein R1is triazolopyrazinyl, triazolopyridinyl, imidazopyridinyl, triazaspirodecanyl, diazaspirodecanyl, or azaspirononanyl, wherein triazolopyrazinyl, triazolopyridinyl, imidazopyridinyl, triazaspirodecanyl, diazaspirodecanyl, and azaspirononanyl are optionally substituted with one or two isopropyl, difluoromethyl, methyl, oxo, or methoxy. 13. The compound of any one of aspects 1-6 or 9 or a pharmaceutically acceptable salt thereof, wherein R1is triazolopyrazinyl, triazolopyridinyl, imidazopyridinyl, diazaspirodecanyl, or azaspirononanyl, wherein triazolopyrazinyl, triazolopyridinyl, imidazopyridinyl, diazaspirodecanyl, and azaspirononanyl are optionally substituted withone or two isopropyl, difluoromethyl, methyl, oxo, or methoxy.14. The compound of any one of aspects 1 to 13 or a pharmaceutically acceptable salt thereof, wherein R1is triazolopyridinyl optionally substituted with one R1a. 15. The compound of any one of aspects 1 to 14 or a pharmaceutically acceptable salt thereof, wherein R1ais C1-6alkyl, oxo, C1-6haloalkyl, C1-6alkoxy. 16. The compound of any one of aspects 1 to 15 or a pharmaceutically acceptable salt thereof, wherein R1ais C1-6alkyl, particularly wherein R1ais methyl. 17. The compound of any one of aspects 1 to 16 or a pharmaceutically acceptable salt thereof, wherein R2is hydrogen. 18. The compound of any one of aspects 1 to 17 or a pharmaceutically acceptable salt thereof, wherein R3is hydrogen. 19. The compound of any one of aspects 1 to 18 or a pharmaceutically acceptable salt thereof, wherein R5is hydrogen. 20. The compound of any one of aspects 1 to 19 or a pharmaceutically acceptable salt thereof, wherein R6is -SCF3, -OCF3, -OCHF2, or hydrogen. 21. The compound of any one of aspects 1 to 20 or a pharmaceutically acceptable salt thereof, wherein R6is -SCF3, or -OCF3. 22. The compound of any one of aspects 1 to 21 or a pharmaceutically acceptable salt thereof, wherein R6is -SCF3.23. The compound of any one of aspects 1 to 22 or a pharmaceutically acceptable salt thereof, wherein R6bis -CF3. 24. The compound of any one of aspects 1 to 23 or a pharmaceutically acceptable salt thereof, wherein R7is -OCF3, -SCF3, -OCHF2, or hydrogen. 25. The compound of any one of aspects 1 to 24 or a pharmaceutically acceptable salt thereof, wherein R7is hydrogen. 26. The compound of any one of aspects 1 to 25 or a pharmaceutically acceptable salt thereof, wherein R7ais -CF3, or -CHF2. 27. The compound of any one of aspects 1 to 26 or a pharmaceutically acceptable salt thereof, wherein R7bis -CF3. 28. The compound of any one of aspects 1 to 27 wherein the compound is of formula (I')

[0007] (I') or a pharmaceutically acceptable salt thereof wherein R1, R2, R3, R5, R6, R7, X1, X2, X3, X4, and X5are as defined in any one of aspects 1 to 27. 29. The compound of any one of aspects 1 to 28 or a pharmaceutically acceptable salt thereof, wherein X1is N, X2is CH, X3is CH, X4is O, X5is N, R1is heterocyclyl, or heteroaryl, wherein heterocyclyl, and heteroaryl, are optionally substituted with one or more R1a, R1ais C1-6alkyl, oxo, C1-6haloalkyl, C1-6alkoxy, R2is hydrogen, R3is hydrogen, R4is OH, R5is hydrogen, R6is -SCF3, and R7is hydrogen. 30. The compound of any one of aspects 1 to 29 or a pharmaceutically acceptable salt thereof, wherein X1is N, X2is CH, X3is CH, X4is O, X5is N, R1is triazolopyridinyl optionally substituted with one R1a, R1ais C1-6alkyl, R2is hydrogen, R3is hydrogen, R4is OH, R5is hydrogen, R6is -SCF3, and R7is hydrogen. 31. The compound of any one of aspects 1 to 30 selected from: (3S,4R)-1-(4-{3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl}benzenesulfonyl)-4-({4- [(trifluoromethyl)sulfanyl]phenyl}Amino)piperidin-3-ol; (3S,4R)-1-{4-[3-(propan-2-yl)imidazo[1,2-a]pyridin-6-yl]benzenesulfonyl}-4-({4- [(trifluoromethyl)sulfanyl]phenyl}Amino)piperidin-3-ol; (3S,4R)-1-(4-{3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl}benzenesulfonyl)-4-({5- [(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol; (3S,4R)-1-{4-[3-(propan-2-yl)imidazo[1,2-a]pyridin-6-yl]benzenesulfonyl}-4-({5- [(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol; (3S,4R)-1-{4-[3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyrazin-6-yl]benzenesulfonyl}- 4-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol; (3S,4R)-1-{4-[3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]benzenesulfonyl}- 4-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol; (3S,4R)-1-{4-[8-methyl-3-(propan-2-yl)imidazo[1,2-a]pyridin-6- yl]benzenesulfonyl}-4-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol; (3S,4R)-1-{4-[3-(difluoromethyl)-[1,2,4]triazolo[4,3-a]pyridin-6- yl]benzenesulfonyl}-4-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol; 8-(4-{[(3S,4R)-3-hydroxy-4-({5-[(trifluoromethyl)sulfanyl]pyridin-2- yl}Amino)piperidin-1-yl]sulfonyl}phenyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione; (3S,4R)-1-(4-{2-methoxy-7-azaspiro[3.5]nonan-7-yl}benzenesulfonyl)-4-({5- [(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol; 8-(4-{[(3S,4R)-3-hydroxy-4-({5-[(trifluoromethyl)sulfanyl]pyridin-2- yl}Amino)piperidin-1-yl]sulfonyl}phenyl)-2,8-diazaspiro[4.5]decan-1-one; (1R,2R,5R)-5-{4-[3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6- yl]benzenesulfonyl}-2-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)cyclohexan-1-ol; (1R,2R,5R)-5-(4-{3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl}benzenesulfonyl)-2- ({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)cyclohexan-1-ol; (1R,2R,5R)-5-(4-{imidazo[1,2-a]pyridin-6-yl}benzenesulfonyl)-2-({5- [(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)cyclohexan-1-ol; (1R,2R,5R)-5-{4-[8-methyl-3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6- yl]benzenesulfonyl}-2-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)cyclohexan-1-ol; (1S,2R,5R)-5-{4-[3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6- yl]benzenesulfonyl}-2-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)cyclohexan-1-ol. 32. The compound of any one of aspects 1 to 31, wherein the compound is (3S,4R)- 1-(4-{3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl}benzenesulfonyl)-4-({5- [(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol. 33. A process of preparation of a compound of formula (I) or (I'), or a pharmaceutically acceptable salt thereof, according to any one of aspects 1 to 32, or a pharmaceutically acceptable salt thereof, wherein X1is N and R4is OH, comprising: reacting compound of formula (II), wherein R5is as defined in any one of aspects 1 to 32,

[0008] (II) with compound of fromula (III), wherein X5, R6,R7are as defined in any one of aspects 1 to 32, and X is halogen, (III) to form compound of formula (IV), wherein R5, R6, R7, and X5are as defined in any one of aspects 1 to 32, (IV) reacting said compound of formula (IV) with acid, to form compound of formula (V), wherein R5, R6, R7, and X5are as defined in any one of aspects 1 to 32, reacting said compound of formula (V) with compound of formula (VI), wherein R2, R3, X2, X3are as defined in any one of aspects 1 to 32, (VI) to form compound of formula (VII), wherein R2, R3, X2, X3, R5, X5, R6, R7are as defined in any one of aspects 1 to 32, reacting said compound of formula (VII) with compound of formula (VIII), wherein R1is as defined in any one of aspects 1 to 32, and R9and R10taken together with the oxygen atom to which they are attached, form a 3- to 14- membered heterocyclyl optionally substituted with one or more C1-6alkyl, in particular optionally substituted with four C1- 6alkyl, (VIII) to form compound of formula (I). 34. A process of preparation of a compound of formula (I) or (I'), or a pharmaceutically acceptable salt thereof, according to any one of aspects 1 to 32, wherein R1is a N-connected heterocyclyl group comprising: reacting compound of formula (V), wherein R5, R6, R7, and X5are as defined in any one of aspects 1 to 32, with compound of formula (XI), wherein R2, R3, X2, X3are as defined in any one of aspects 1 to 32, (XI) to form compound of formula (XII), wherein R2, R3, X2, X3, R5, X5, R6, R7are as defined in any one of aspects 1 to 32, reacting said compound of formula (XII) with compound of formula (XIII), wherein R1is as defined in any one of aspects 1 to 32, (XIII) to form compound of formula (I). 35. A process of preparation of a compound of formula (I) or (I'), or a pharmaceutically acceptable salt thereof, according to any one of aspects 1 to 32, wherein X1is CH, and R4is OH, comprising: reacting compound of formula (XIV), (XIV)with methoxy(methyl)amine hydrochloride to form compound of formula (XV), (XV) reacting said compound (XV) with a base, to form compound of formula (XVI), (XVI) reacting said compound of formula (XVI) with a Grubbs catalyst, to form compound (XVII), wherein R5is as defined in any one of aspects 1 to 32, reacting said compound (XVII) with compound (XVIII), wherein X2, X3, R2, R3are as defined in any one of aspects 1 to 32, (XVIII) to form compound of formula (XIX) wherein X2, X3, R2, R3, R5, are as defined in any one of aspects 1 to 32, (XIX) reacting said compound of formula (XIX) with a reducing agent, to form compound of formula (XX), wherein X2, X3, R2, R3, R5, are as defined in any one of aspects 1 to 32, (XX) reacting said compound (XX) with an oxidant, to form compound of formula (XXI), wherein X2, X3, R2, R3, R5, are as defined in any one of aspects 1 to 32,

[0009] (XXI) reacting said compound (XXI) with compound of formula (VIII), wherein R1is as defined in any one of aspects 1 to 32, and R9and R10taken together with the oxygen atom to which they are attached, form a 3- to 14- membered heterocyclyl optionally substituted with one or more C1-6alkyl, in particular optionally substituted with four C1-6alkyl, to form compound of formula (XXII), wherein X2, X3, R2, R3, R5, R1, are as defined in any one of aspects 1 to 32, (XXII) reacting said compound of formula (XXII) with acid to form compound of formula (XXIII), wherein X2, X3, R2, R3, R5, R1, are as defined in any one of aspects 1 to 32, (XXIII) reacting said compound of formula (XXIII) with compound of formula (III), wherein X5, R6, R7are as defined in any one of aspects 1 to 32, and X is halogen, (III) to form compound of formula (I). 36. A compound according to any one of aspects 1 to 32, or a pharmaceutically acceptable salt thereof, when manufactured according to the process of any one of the aspect 33. 37. A compound according to any one of aspects 1 to 32, or a pharmaceutically acceptable salt thereof, when manufactured according to the process of any one of the aspect 33 to 35. 38. A compound according to any one of aspects 1 to 32, or a pharmaceutically acceptable salt thereof, for use as therapeutically active substance. 39. A pharmaceutical composition comprising a compound according to any one of aspects 1 to 32, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. 40. The pharmaceutical composition according to aspect 39, further comprising an additional therapeutic agent. 41. A compound according to any one of aspects 1 to 32, or a pharmaceutically acceptable salt thereof, for use in the treatment, prevention and / or delay of progression of an inflammatory autoimmune disease. 42. A compound according to any one of aspects 1 to 32, or a pharmaceutically acceptable salt thereof, for use in the treatment, prevention and / or delay of progression of psoriatic diseases, asthma, Inflammatory Bowel Diseases (IBD), Crohn’s disease, Obstructive Lung Diseases ulcerative colitis, rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis. 43. A compound according to any one of aspects 1 to 32, or a pharmaceutically acceptable salt thereof, for use in the treatment, prevention and / or delay of progression ofInflammatory Bowel Diseases (IBD) or Obstructive Lung Diseases.44. The use of a compound according to any one of aspects 1 to 32, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for thetreatment, prevention and / or delay of an inflammatory autoimmune disease.45. The use of a compound according to any one of aspects 1 to 32, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment, prevention and / or delay of Inflammatory Bowel Diseases (IBD) or Obstructive Lung Diseases. 46. A method for the treatment, prevention and / or delay of progression of an inflammatory autoimmune disease, which method comprises administering a therapeutically effective amount of a compound according to any one of aspects 1 to 32, or a pharmaceutically acceptable salt thereof. 47. A method for the treatment, prevention and / or delay of progression of Inflammatory Bowel Diseases (IBD) or Obstructive Lung Diseases, which method comprises administering a therapeutically effective amount of a compound according to any one of aspects 1 to 32, or a pharmaceutically acceptable salt thereof.

Claims

CLAIMS 1. A compound of formula (I)X1is CH or N; X2is CH or N; X3is CH or N; X4is O or NH; X5is CH or N; R1is aryl, heterocyclyl, or heteroaryl, wherein aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more R1a; R1ais C1-6alkyl, oxo, cyano, carbamoyl, C1-6haloalkyl, C1-6alkoxy, C1-6alkylcarbamoyl-, C1-6alkoxyC1-6alkyl-, C3‑6cycloalkyl, or heterocyclyl; R2is hydrogen or halogen; R3is hydrogen or halogen; R4is OH; R5is hydrogen or C1-6alkyl; R6is -OR6a, -SR6b, or hydrogen; R6ais C1-6haloalkyl; R6bis C1-6haloalkyl; R7is -OR7a, -SR7b, or hydrogen; R7ais C1-6haloalkyl; R7bis C1-6haloalkyl; provided that R6and R7must be different, and R6or R7is hydrogen, or pharmaceutically acceptable salts thereof.

2. The compound of claim 1 wherein X1is CH.

3. The compound of claim 1 wherein X1is N.

4. The compound of any one of claims 1 to 3 wherein X4is O.

5. The compound of any one of claims 1 to 4 wherein X5is CH.

6. The compound of any one of claims 1 to 4 wherein X5is N.

7. The compound of any one of claims 1 to 6, or a pharmaceutically acceptable salt thereof, wherein X1is N, X2is CH, X3is CH, X4is O, and X5is CH.

8. The compound of any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof, wherein X1is N, X2is CH, X3is CH, X4is O, and X5is N.

9. The compound of any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof, wherein R1is heterocyclyl, or heteroaryl, wherein heterocyclyl, and heteroaryl, are optionally substituted with one or more R1a.

10. The compound of any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof, wherein R1is triazolopyrazinyl, triazolopyridinyl, imidazopyridinyl, triazaspirodecanyl, diazaspirodecanyl, or azaspirononanyl, wherein triazolopyrazinyl, triazolopyridinyl, imidazopyridinyl, triazaspirodecanyl, diazaspirodecanyl, and azaspirononanyl are optionally substituted with one or more R1a.

11. The compound of any one of claims 1- 9 or a pharmaceutically acceptable salt thereof, wherein R1is triazolopyrazinyl, triazolopyridinyl, imidazopyridinyl, triazaspirodecanyl, diazaspirodecanyl, or azaspirononanyl, wherein triazolopyrazinyl, triazolopyridinyl,imidazopyridinyl, triazaspirodecanyl, diazaspirodecanyl, and azaspirononanyl are optionallysubstituted with one or two isopropyl, difluoromethyl, methyl, oxo, or methoxy.

12. The compound of any one of claims 1 to 11 or a pharmaceutically acceptable salt thereof, wherein R1is triazolopyridinyl optionally substituted with one R1a.

13. The compound of any one of claims 1 to 12 or a pharmaceutically acceptable salt thereof, wherein R1ais C1-6alkyl, oxo, C1-6haloalkyl, C1-6alkoxy.

14. The compound of any one of claims 1 to 13 or a pharmaceutically acceptable salt thereof, wherein R1ais C1-6alkyl, particularly wherein R1ais methyl.

15. The compound of any one of claims 1 to 14 or a pharmaceutically acceptable salt thereof, wherein R2is hydrogen.

16. The compound of any one of claims 1 to 15 or a pharmaceutically acceptable salt thereof, wherein R3is hydrogen.

17. The compound of any one of claims 1 to 16 or a pharmaceutically acceptable salt thereof, wherein R5is hydrogen.

18. The compound of any one of claims 1 to 17 or a pharmaceutically acceptable salt thereof, wherein R6is -SCF3, -OCF3, -OCHF2, or hydrogen.

19. The compound of any one of claims 1 to 18 or a pharmaceutically acceptable salt thereof, wherein R6is -SCF3, or -OCF3.

20. The compound of any one of claims 1 to 19 or a pharmaceutically acceptable salt thereof, wherein R6is -SCF3.

21. The compound of any one of claims 1 to 20 or a pharmaceutically acceptable salt thereof, wherein R6bis -CF3.

22. The compound of any one of claims 1 to 21 or a pharmaceutically acceptable salt thereof, wherein R7is -OCF3, -SCF3, -OCHF2, or hydrogen.

23. The compound of any one of claims 1 to 22 or a pharmaceutically acceptable salt thereof, wherein R7is hydrogen.

24. The compound of any one of claims 1 to 23 or a pharmaceutically acceptable salt thereof, wherein R7ais -CF3, or -CHF2.

25. The compound of any one of claims 1 to 24 or a pharmaceutically acceptable salt thereof, wherein R7bis -CF3.

26. The compound of any one of claims 1 to 25 wherein the compound is of formula (I')or a pharmaceutically acceptable salt thereof wherein R1, R2, R3, R5, R6, R7, X1, X2, X3, X4, and X5are as defined in any one of claims 1 to 25.

27. The compound of any one of claims 1 to 26 or a pharmaceutically acceptable salt thereof, wherein X1is N, X2is CH, X3is CH, X4is O, X5is N, R1is heterocyclyl, or heteroaryl, wherein heterocyclyl, and heteroaryl, are optionally substituted with one or more R1a, R1ais C1-6alkyl, oxo, C1-6haloalkyl, C1-6alkoxy,R2is hydrogen, R3is hydrogen, R4is OH, R5is hydrogen, R6is -SCF3, and R7is hydrogen.

28. The compound of any one of claims 1 to 27 or a pharmaceutically acceptable salt thereof, wherein X1is N, X2is CH, X3is CH, X4is O, X5is N, R1is triazolopyridinyl optionally substituted with one R1a, R1ais C1-6alkyl, R2is hydrogen, R3is hydrogen, R4is OH, R5is hydrogen, R6is -SCF3, and R7is hydrogen.

29. The compound of any one of claims 1 to 28 selected from: (3S,4R)-1-(4-{3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl}benzenesulfonyl)-4-({4- [(trifluoromethyl)sulfanyl]phenyl}Amino)piperidin-3-ol; (3S,4R)-1-{4-[3-(propan-2-yl)imidazo[1,2-a]pyridin-6-yl]benzenesulfonyl}-4-({4- [(trifluoromethyl)sulfanyl]phenyl}Amino)piperidin-3-ol; (3S,4R)-1-(4-{3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl}benzenesulfonyl)-4-({5- [(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol; (3S,4R)-1-{4-[3-(propan-2-yl)imidazo[1,2-a]pyridin-6-yl]benzenesulfonyl}-4-({5- [(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol; (3S,4R)-1-{4-[3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyrazin-6-yl]benzenesulfonyl}- 4-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol; (3S,4R)-1-{4-[3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]benzenesulfonyl}- 4-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol;(3S,4R)-1-{4-[8-methyl-3-(propan-2-yl)imidazo[1,2-a]pyridin-6- yl]benzenesulfonyl}-4-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol; (3S,4R)-1-{4-[3-(difluoromethyl)-[1,2,4]triazolo[4,3-a]pyridin-6- yl]benzenesulfonyl}-4-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol; 8-(4-{[(3S,4R)-3-hydroxy-4-({5-[(trifluoromethyl)sulfanyl]pyridin-2- yl}Amino)piperidin-1-yl]sulfonyl}phenyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione; (3S,4R)-1-(4-{2-methoxy-7-azaspiro[3.5]nonan-7-yl}benzenesulfonyl)-4-({5- [(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol; 8-(4-{[(3S,4R)-3-hydroxy-4-({5-[(trifluoromethyl)sulfanyl]pyridin-2- yl}Amino)piperidin-1-yl]sulfonyl}phenyl)-2,8-diazaspiro[4.5]decan-1-one; (1R,2R,5R)-5-{4-[3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6- yl]benzenesulfonyl}-2-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)cyclohexan-1-ol; (1R,2R,5R)-5-(4-{3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl}benzenesulfonyl)-2- ({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)cyclohexan-1-ol; (1R,2R,5R)-5-(4-{imidazo[1,2-a]pyridin-6-yl}benzenesulfonyl)-2-({5- [(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)cyclohexan-1-ol; (1R,2R,5R)-5-{4-[8-methyl-3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6- yl]benzenesulfonyl}-2-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)cyclohexan-1-ol; (1S,2R,5R)-5-{4-[3-(propan-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6- yl]benzenesulfonyl}-2-({5-[(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)cyclohexan-1-ol.

30. The compound of any one of claims 1 to 29, wherein the compound is (3S,4R)-1-(4-{3- methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl}benzenesulfonyl)-4-({5- [(trifluoromethyl)sulfanyl]pyridin-2-yl}Amino)piperidin-3-ol.

31. A process of preparation of a compound of formula (I) or (I'), or a pharmaceutically acceptable salt thereof, according to any one of claims 1 to 30, or a pharmaceutically acceptable salt thereof, wherein X1is N and R4is OH, comprising: reacting compound of formula (II), wherein R5is as defined in any one of claims 1 to 30,with compound of fromula (III), wherein X5R6,R7are as defined in any one of claims 1 to 30, and X is halogen,to form compound of formula , R6, R7, and X5are as defined in any one of claims 1 to 30,reacting said compound of to form compound of formula (V), wherein R5, R6, R7, and X5are as defined in any one of claims 1 to 30,reacting said compound of formula (V) with compound of formula (VI), wherein R 2,R3, X2, X3are as defined in any one of claims 1 to 30,to form compound of formula , R3, X2, X3, R5, X5, R6, R7are as defined in any one of claims 1 to 30,reacting said compound of of formula (VIII), wherein R1is as defined in any one of claims 1 to 30, and R9and R10taken together with the oxygen atom to which they are attached, form a 3- to 14- membered heterocyclyl optionally substituted with one or more C1-6alkyl, in particular optionally substituted with four C1-6alkyl,(VIII) to form compound of formula (I).

32. A process of preparation of a compound of formula (I) or (I'), or a pharmaceuticallyacceptable salt thereof, according to any one of claims 1 to 30, wherein R 1 is a N-connectedheterocyclyl group comprising: reacting compound of formula (V), wherein R5, R6, R7, and X5are as defined in any one of claims 1 to 30,with compound of formula , X2, X3are as defined in any one of claims 1 to 30,to form compound of formula , R3, X2, X3, R5, X5, R6, R7are as defined in any one of claims 1 to 30,reacting said compound of formula (XII) with compound of formula (XIII), wherein R1is as defined in any one of claims 1 to 30, (XIII) to form compound of formula (I).

33. A process of preparation of a compound of formula (I) or (I'), or a pharmaceutically acceptable salt thereof, according to any one of claims 1 to 30, wherein X1is CH, and R4is OH, comprising: reacting compound of formula (XIV),with methoxy(methyl)amine compound of formula (XV),<img src='' class="img-anchor img-center" img-id="IMGF000088_0002" / >(XV) reacting said compound (XV) with a base, to form compound of formula (XVI),reacting said compound of a Grubbs catalyst, to form compound (XVII), wherein R5is as defined in any one of claims 1 to 30,reacting said compound , wherein X2, X3, R2, R3are as defined in any one of claims 1 to 30,(XVIII) to form compound of formula (XIX) wherein X2, X3, R2, R3, R5, are as defined in any one of claims 1 to 30,reacting said compound of formula (XIX) with a reducing agent, to form compound of formula (XIX), wherein X2, X3, R2, R3, R5, are as defined in any one of claims 1 to 30,reacting said compound (XX) an to form compound of formula (XXI), wherein X2, X3, R2, R3, R5, are as defined in any one of claims 1 to 30,<img src='' class="img-anchor img-center" img-id="IMGF000090_0002" / >(XXI) reacting said compound (XXI) with compound of formula (VIII), wherein R1is as defined in any one of claims 1 to 30, and R9and R10taken together with the oxygen atom to which they are attached, form a 3- to 14- membered heterocyclyl optionally substituted with one or more C1-6alkyl, in particular optionally substituted with four C1-6alkyl,to form compound of formula , X3, R2, R3, R5, R1, are as defined in any one of claims 1 to 30,reacting said compound of acid to form compound of formula (XXIII), wherein X2, X3, R2, R3, R5, R1, are as defined in any one of claims 1 to 30,<img src='' class="img-anchor img-center" img-id="IMGF000091_0003" / >(XXIII) reacting said compound of formula (XXIII) with compound of formula (III), wherein X5, R6, R7are as defined in any one of claims 1 to 30, and X is halogen,to form compound of formula .

34. A compound according to any one of claims 1 to 30, or a pharmaceutically acceptable salt thereof, when manufactured according to the process of any one of the claims 31 to 33.

35. A compound according to any one of claims 1 to 30, or a pharmaceutically acceptable salt thereof, for use as therapeutically active substance.

36. A pharmaceutical composition comprising a compound according to any one of claims 1 to 30, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

37. The pharmaceutical composition according to claim 36, further comprising an additional therapeutic agent.

38. A compound according to any one of claims 1 to 30, or a pharmaceutically acceptable salt thereof, for use in the treatment, prevention and / or delay of progression of an inflammatory autoimmune disease.

39. A compound according to any one of claims 1 to 30, or a pharmaceutically acceptable salt thereof, for use in the treatment, prevention and / or delay of progression of psoriatic diseases, asthma, Inflammatory Bowel Diseases (IBD), Crohn’s disease, Obstructive Lung Diseases ulcerative colitis, rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis.

40. A compound according to any one of claims 1 to 30, or a pharmaceutically acceptable salt thereof, for use in the treatment, prevention and / or delay of progression ofInflammatory Bowel Diseases (IBD) or Obstructive Lung Diseases.

41. The use of a compound according to any one of claims 1 to 30, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment, prevention and / or delay of an inflammatory autoimmune disease.

42. The use of a compound according to any one of claims 1 to 30, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment, preventionand / or delay of Inflammatory Bowel Diseases (IBD) or Obstructive Lung Diseases.

43. A method for the treatment, prevention and / or delay of progression of an inflammatory autoimmune disease, which method comprises administering a therapeutically effective amount of a compound according to any one of claims 1 to 30, or a pharmaceutically acceptable salt thereof.

44. A method for the treatment, prevention and / or delay of progression of Inflammatory Bowel Diseases (IBD) or Obstructive Lung Diseases, which method comprises administering a therapeutically effective amount of a compound according to any one of claims 1 to 30, or a pharmaceutically acceptable salt thereof.

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