5-[5-(2-hydroxyphenyl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one derivatives as nlpr3 inhibitors for the treatment of inflammatory diseases

Abstract

The invention relates to novel compounds having the general formula (I), wherein R1, R2, R9, A1, Y1, Y2 and Z are as described herein, composition including the compounds and methods of using the compounds.

Description

[0001]Case P38441 Novel Compounds Field of the Invention The present invention relates to organic compounds useful for therapy and / or prophylaxis in a mammal, and in particular to compounds that modulate NLRP3 inhibition. The present invention provides novel compounds of formula I wherein, R1is halo, haloalkyl or alkyl, and R9is H, or R1and R9and the atoms to which they are attached form a 5-membered cycloalkyl or a 5- membered heterocycle comprising 1 O heteroatom; R2is methyl or methoxyalkyl; A1is –CH- or –N-; Y1 is CH-Rcor NRnand Y2 is CH-Rcor NRn, wherein at least one of Y1 and Y2 must be NRn; Rcis H, OH, alkyl, hydroxyalkyl, or alkoxy; Rnis H, alkyl or hydroxyalkyl; Z is H, OH, alkoxy or hydroxyalkyl, wherein if R1is halo or haloalkyl, then one of Z, Rcor Rnmust not be H; and pharmaceutically acceptable salts thereof. Furthermore, the invention includes all racemic mixtures, all their corresponding enantiomers and / or optical isomers. EJ / April 2024 Background of the Invention The NOD-like receptor (NLR) family, pyrin domain–containing protein 3 (NLRP3) inflammasome is a component of the inflammatory process, and its aberrant activity is pathogenic in inherited disorders such as cryopyrin-associated periodic syndromes (CAPS) and complex diseases such as multiple sclerosis, type 2 diabetes, Alzheimer’s disease and atherosclerosis. NLRP3 is an intracellular signaling molecule that senses many pathogen-derived, environmental and host-derived factors. Upon activation, NLRP3 binds to apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC). ASC then polymerises to form a large aggregate known as an ASC speck. Polymerised ASC in turn interacts with the cysteine protease caspase-1 to form a complex termed the inflammasome. This results in the activation of caspase-1, which cleaves the precursor forms of the proinflammatory cytokines IL- 1β and IL-18 (termed pro-IL-1β and pro-IL-18 respectively) to thereby activate these cytokines. Caspase-1 also mediates a type of inflammatory cell death known as pyroptosis. The ASC speck can also recruit and activate caspase-8, which can process pro-IL-1β and pro-IL-18 and trigger apoptotic cell death. Caspase-1 cleaves pro-IL-1β and pro-IL-18 to their active forms, which are secreted from the cell. Active caspase-1 also cleaves gasdermin-D to trigger pyroptosis. Through its control of the pyroptotic cell death pathway, caspase-1 also mediates the release of alarmin molecules such as IL-33 and high mobility group box 1 protein (HMGB1). Caspase-1 also cleaves intracellular IL- 1R2 resulting in its degradation and allowing the release of IL-1α. In human cells caspase-1 may also control the processing and secretion of IL-37. A number of other caspase-1 substrates such as components of the cytoskeleton and glycolysis pathway may contribute to caspase-1- dependent inflammation. NLRP3-dependent ASC specks are released into the extracellular environment where they can activate caspase-1, induce processing of caspase-1 substrates and propagate inflammation. Active cytokines derived from NLRP3 inflammasome activation are important drivers of inflammation and interact with other cytokine pathways to shape the immune response to infection and injury. For example, IL-1β signalling induces the secretion of the pro-inflammatory cytokines IL-6 and TNF. IL-1β and IL-18 synergise with IL-23 to induce IL-17 production by memory CD4 Th17 cells and by γδ T cells in the absence of T cell receptor engagement. IL-18 and IL-12 also synergise to induce IFN-γ production from memory T cells and NK cells driving a Th1 response. The inherited CAPS diseases Muckle–Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS) and neonatal-onset multisystem inflammatory disease (NOMID) are caused by gain-of-function mutations in NLRP3, thus defining NLRP3 as a critical component of the inflammatory process. NLRP3 has also been implicated in the pathogenesis of a number of complex diseases, notably including metabolic disorders such as type 2 diabetes, atherosclerosis, obesity and gout. A role for NLRP3 in diseases of the central nervous system is emerging, and lung diseases have also been shown to be influenced by NLRP3. NLRP3 has also been suggested to have a role in a number of central nervous system conditions, including Parkinson's disease (PD), Alzheimer's disease (AD), dementia, Huntington's disease, cerebral malaria, brain injury from pneumococcal meningitis (Walsh et al., Nature Reviews, 15: 84-97, 2014, and Dempsey et al. Brain. Behav. Immun.201761: 306-316). NLRP3 has also been shown to play a role in a number of lung diseases including chronic obstructive pulmonary disorder (COPD), asthma (including steroid- resistant asthma), asbestosis, and silicosis (De Nardo et al., Am. J. Pathol., 184: 42-54, 2014 and Kim et al. Am J Respir Crit Care Med.2017196(3): 283-97). Furthermore, NLRP3 has a role in the development of liver disease, kidney disease and aging. Many of these associations were defined using Nlrp3− / −mice, but there have also been insights into the specific activation of NLRP3 in these diseases. In type 2 diabetes mellitus (T2D), the deposition of islet amyloid polypeptide in the pancreas activates NLRP3 and IL-1β signalling, resulting in cell death and inflammation. Several small molecules have been shown to inhibit the NLRP3 inflammasome. Glyburide inhibits IL-1β production at micromolar concentrations in response to the activation of NLRP3 but not NLRC4 or NLRP1. Other previously characterised weak NLRP3 inhibitors include parthenolide, 3,4-methylenedioxy-β-nitrostyrene and dimethyl sulfoxide (DMSO), although these agents have limited potency and are nonspecific. Current treatments for NLRP3-related diseases include biologic agents that target IL-1. These are the recombinant IL-1 receptor antagonist anakinra, the neutralizing IL-1β antibody canakinumab and the soluble decoy IL-1 receptor rilonacept. These approaches have proven successful in the treatment of CAPS, and these biologic agents have been used in clinical trials for other IL-1β- associated diseases. There is a need to provide compounds with improved pharmacological and / or physiological and / or physicochemical properties and / or those that provide a useful alternative to known compounds. The invention presented here demonstrates enhanced potency in combination with increased solubility to provide inhibitors with an overall improved profile. Summary of the Invention The present invention provides novel compounds of formula I wherein, R1is halo, haloalkyl, or alkyl, and R9is H, or R1and R9and the atoms to which they are attached form a 5-membered cycloalkyl or a 5- membered heterocycle comprising 1 O heteroatom; R2is methyl or methoxyalkyl; A1 is –CH- or –N-; Y1is CH-Rcor NRnand Y2is CH-Rcor NRn, wherein at least one of Y1and Y2must be NRn; Rcis H, OH, alkyl, hydroxyalkyl, or alkoxy; Rnis H, alkyl or hydroxyalkyl; Z is H, OH, alkoxy or hydroxyalkyl, wherein if R1is halo or haloalykl, then one of Z, Rcor Rnmust not be H; and pharmaceutically acceptable salts thereof. The term “alkyl” denotes a monovalent linear or branched saturated hydrocarbon group of 1 to 6 carbon atoms. In some embodiments, if not otherwise described, alkyl comprises 1 to 6 carbon atoms (C1-6-alkyl), or 1 to 4 carbon atoms (C1-4-alkyl). Examples of C1-6-alkyl include methyl, ethyl, propyl, isopropyl, n-butyl, iso-butyl, sec-butyl, tert-butyl and pentyl. Particular alkyl group is methyl. The term “alkoxy” denotes a group of the formula -O-R’, wherein R’ is a C1-6-alkyl group. Examples of C1-6-alkoxy groups include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy and tert-butoxy. Particular alkoxy group is methoxy. The term “alkoxyalkyl” denotes an alkyl group wherein one of the hydrogen atoms of the alkyl group have been replaced by an alkoxy group. Examples of alkoxyalkyl are methoxymethyl and methoxyethyl. Particular example of alkoxyalkyl is methoxymethyl. The term “cycloalkyl” denotes monocyclic or polycyclic saturated or partially unsaturated, non-aromatic hydrocarbon. In some embodiments, unless otherwise described, cycloalkyl comprises 3 to 8 carbon atoms, 3 to 6 carbon atoms, or 3 to 5 carbon atoms. In some embodiments, cycloalkyl is a saturated monocyclic or polycyclic hydrocarbon. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, and the like. Particular example is cyclopentyl. The term “halogen”, “halide” and “halo” are used interchangeably herein and denote fluoro, chloro, bromo or iodo. Particular examples of halo is chloro. The term “haloalkyl” denotes a C1-6-alkyl group wherein at least one of the hydrogen atoms of the C1-6-alkyl group has been replaced by the same or different halogen atoms. Examples of haloalkyl include fluoromethyl, difluoromethyl and trifluoromethyl. Particular example of haloalkyl is trifluoromethyl. The term “heterocycle ring” denotes a monovalent saturated or partly unsaturated mono- or bicyclic ring system of 4 to 9 ring atoms, comprising 1, 2, or 3 ring heteroatoms selected from N, O and S, the remaining ring atoms being carbon. Examples for monocyclic saturated heterocycle rings are azetidinyl, diazepanyl, pyrrolidinyl, tetrahydrofuranyl, pyrazolidinyl, imidazolidinyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, piperidinyl, tetrahydropyranyl, tetrahydrothiopyranyl, morpholinyl, and piperazinyl. Examples of polycyclic saturated heterocycle rings are azaspiroheptanyl, diazaspiroheptanyl, azaspirooctanyl, diazospirooctanyl, diazaspirononanyl, oxaazaspirooctanyl, and oxadiazaspirononanyl. Particular example is tetrahydrofuranyl. The term “hydroxy” denotes a -OH group. The term “hydroxyalkyl” denotes an alkyl group wherein at least one of the hydrogen atoms of the alkyl group has been replaced by a hydroxy group. Examples of hydroxyalkyl include hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxymethylethyl, hydroxymethylpropyl and dihydroxypropyl. The term “cyano” denotes a –C≡N group. The term “pharmaceutically acceptable salts'' 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 trifluoroacetic acid, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, particularly hydrochloric acid, and organic acids such as formic acid, 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. In addition these salts may be prepared from addition of an inorganic base or an organic base to the free acid. Salts derived from an inorganic base include, but are not limited to, the sodium, potassium, lithium, ammonium, calcium, magnesium salts. Salts derived from organic bases include, but are not limited to salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, lysine, arginine, N-ethylpiperidine, piperidine, polyamine resins. The compound of formula I can also be present in the form of zwitterions. Particularly preferred pharmaceutically acceptable salts of compounds of formula I are the salts formed with formic acid and the salts formed with hydrochloric acid yielding a hydrochloride, dihydrochloride or trihydrochloride salt. The abbreviation uM means microMolar and is equivalent to the symbol µM. The abbreviation uL means microliter and is equivalent to the symbol µL. The abbreviation ug means microgram and is equivalent to the symbol µg. The compounds of formula I can contain several asymmetric centers and can be present in the form of optically pure enantiomers, mixtures of enantiomers such as, for example, racemates, optically pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates or mixtures of diastereoisomeric racemates. According to the Cahn-Ingold-Prelog Convention the asymmetric carbon atom can be of the "R" or "S" configuration. Also an embodiment of the present invention provides compounds according to formula I as described herein and pharmaceutically acceptable salts or esters thereof, in particular compounds according to formula I as described herein and pharmaceutically acceptable salts thereof, more particularly compounds according to formula I as described herein. An embodiment of the present invention provides compounds according to formula I as described herein, wherein R1is haloalkyl and R9is H, or R1and R9and the atoms to which they are attached form a 5-membered cycloalkyl or a 5-membered heterocycle comprising 1 O heteroatom. An embodiment of the present invention provides compounds according to formula I as described herein, wherein R2is methyl. An embodiment of the present invention provides compounds according to formula I as described herein, wherein A1is –CH-. An embodiment of the present invention provides compounds according to formula I as described herein, wherein Rcis H, OH, hydroxyalkyl or alkoxy. An embodiment of the present invention provides compounds according to formula I as described herein, wherein Rcis H or alkoxy. An embodiment of the present invention provides compounds according to formula I as described herein, wherein Rnis H, or hydroxyalkyl. An embodiment of the present invention provides compounds according to formula I as described herein, wherein Rnis H. An embodiment of the present invention provides compounds according to formula I as described herein, wherein Z is H or OH, wherein if R1is haloalkyl, then one of Z, Rcor Rnmust not be H. An embodiment of the present invention provides compounds according to formula I as described herein, wherein one of Z or Rcis alkoxy. An embodiment of the present invention provides compounds according to formula I as described herein, wherein both Y1 and Y2 are N. An embodiment of the present invention provides compounds according to formula I as described herein, wherein, R1is halo or haloalkyl, and R9is H, or R1and R9and the atoms to which they are attached form a 5-membered cycloalkyl or a 5- membered heterocycle comprising 1 O heteroatom; R2is methyl or methoxyalkyl; A1is –CH- or –N-; Y1is CH-Rcor NRnand Y2is CH-Rcor NRn, wherein at least one of Y1and Y2must be NRn; Rcis H, OH, alkyl, hydroxyalkyl, or alkoxy; Rnis H, alkyl or hydroxyalkyl; Z is H, OH, alkoxy or hydroxyalkyl, wherein one of Z or Rcmust be alkoxy; and pharmaceutically acceptable salts thereof. An embodiment of the present invention provides compounds according to formula I as described herein, wherein, R1is halo or haloalkyl, and R9is H, or R1and R9and the atoms to which they are attached form a 5-membered cycloalkyl or a 5- membered heterocycle comprising 1 O heteroatom; R2is methyl; A1is –CH-; Y1is CH-Rcor NRnand Y2is CH-Rcor NRn, wherein one of Y1and Y2must be NRn; Rcis H or alkoxy; Rnis H or hydroxyalkyl; Z is H, OH, wherein one of Z or Rcmust be alkoxy; and pharmaceutically acceptable salts thereof. An embodiment of the present invention provides compounds according to formula I as described herein, wherein, R1is haloalkyl, and R9is H, or R1and R9and the atoms to which they are attached form a 5-membered cycloalkyl or a 5- membered heterocycle comprising 1 O heteroatom; R2is methyl; A1is –CH-; Y1is CH-Rcor NRnand Y2is CH-Rcor NRn, wherein one of Y1and Y2is NRn; Rcis H or alkoxy; Rnis H or hydroxyalkyl; Z is H or OH, wherein if R1is haloalykl, then one of Z, Rcor Rnmust not be H; and pharmaceutically acceptable salts thereof. An embodiment of the present invention provides compounds according to formula I as described herein, wherein, R1is haloalkyl, and R9is H, or R1and R9and the atoms to which they are attached form a 5-membered cycloalkyl or a 5- membered heterocycle comprising 1 O heteroatom; R2is methyl; A1 is –CH-; Y1is CH-Rcor NRnand Y2is CH-Rcor NRn, wherein one of Y1and Y2is NRn; Rcis H or alkoxy; Rnis H; Z is H or OH, wherein if R1is haloalykl, then one of Z, Rcor Rnmust not be H; and pharmaceutically acceptable salts thereof. An embodiment of the present invention provides compounds according to formula I as described herein, wherein, R1and R9and the atoms to which they are attached form a 5-membered cycloalkyl or a 5 membered heterocycle comprising 1 O heteroatom; R2is methyl; A1is –CH-; Y1is CH-Rcor NRnand Y2is CH-Rcor NRn, wherein one of Y1and Y2is NRn; Rcis H; Rnis H; Z is H; and pharmaceutically acceptable salts thereof. An embodiment of the present invention provides compounds according to formula I as described herein, wherein, R1and R9and the atoms to which they are attached form a 5-membered cycloalkyl or a 5 membered heterocycle comprising 1 O heteroatom; R2is CH2-methoxy or methyl; A1 is –CH-; Y1 and Y2 are both N; Rcis H; Rnis H; Z is H; and pharmaceutically acceptable salts thereof. Particular examples of compounds of formula I as described herein are selected from 5-[5-(4-Hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one; (5S)-5-[5-(4-Hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one; (5R)-5-[5-(4-Hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one; rel-(3R,5R)-5-[5-[2-Hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin- 2-yl]-3-methoxy-piperidin-2-one or rel-(3S,5R)-5-[5-[2-hydroxy-6-methyl-4- (trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin-2-yl]-3-methoxy-piperidin-2-one; rel-(3S,5R)-5-[5-[2-Hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin- 2-yl]-3-methoxy-piperidin-2-one or rel-(3R,5R)-5-[5-[2-hydroxy-6-methyl-4- (trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin-2-yl]-3-methoxy-piperidin-2-one; (5S)-5-[5-(4-Hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2- yl]piperidin-2-one; (5R)-5-[5-(4-Hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2- yl]piperidin-2-one; 5-hydroxy-5-[5-[2-Hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin- 2-yl]piperidin-2-one; and pharmaceutically acceptable salts thereof. Other particular examples of compounds of formula I as described herein are selected from 5-[5-(2-hydroxy-4,6-dimethyl-phenyl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one; (5S)-5-[5-(2-hydroxy-4,6-dimethyl-phenyl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5R)-5-[5-(2-hydroxy-4,6-dimethyl-phenyl)oxazolo[4,5-b]pyridin-2-yl]piperidin- 2-one; (5R)-5-[5-(2-hydroxy-4,6-dimethyl-phenyl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5S)-5-[5-(2-hydroxy-4,6-dimethyl-phenyl)oxazolo[4,5-b]pyridin-2-yl]piperidin- 2-one; 5-[5-[4-Hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5-yl]oxazolo[4,5-b]pyridin- 2-yl]hexahydropyrimidin-2-one; 5-[5-(4-hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2- yl]hexahydropyrimidin-2-one; 1-(2-hydroxyethyl)-5-[5-[4-hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5- yl]oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one; (5R)-1-(2-hydroxyethyl)-5-[5-[4-hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5- yl]oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5S)-1-(2-hydroxyethyl)-5-[5-[4- hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5-yl]oxazolo[4,5-b]pyridin- 2-yl]piperidin-2-one; (5S)-1-(2-hydroxyethyl)-5-[5-[4-hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5- yl]oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5R)-1-(2-hydroxyethyl)-5-[5- [4-hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5-yl]oxazolo[4,5- b]pyridin-2-yl]piperidin-2-one; 1-(2-hydroxyethyl)-5-[5-(4-hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5- b]pyridin-2-yl]piperidin-2-one; (5R)-1-(2-hydroxyethyl)-5-[5-[4-hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5- yl]oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5S)-1-(2-hydroxyethyl)-5-[5-[4- hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5-yl]oxazolo[4,5-b]pyridin- 2-yl]piperidin-2-one; (5S)-1-(2-hydroxyethyl)-5-[5-[4-hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5- yl]oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5R)-1-(2-hydroxyethyl)-5-[5- [4-hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5-yl]oxazolo[4,5- b]pyridin-2-yl]piperidin-2-one; 4-(hydroxymethyl)-5-[5-[2-hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5- b]pyridin-2-yl]piperidin-2-one; 3-hydroxy-5-[5-[2-hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin-2- yl]piperidin-2-one; 5-[5-(4-Hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyrazin-2- yl]hexahydropyrimidin-2-one;formic acid; and pharmaceutically acceptable salts thereof. An other particular example of a compound of formula I as described herein is 1-(2- Hydroxyethyl)-5-[5-[2-hydroxy-6-methyl-4-(trifluoromethyl)phenyl]- oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one. An other particular example of a compound of formula I as described herein is a pharmaceutically acceptable salt of 1-(2-Hydroxyethyl)-5-[5-[2-hydroxy-6- methyl-4-(trifluoromethyl)phenyl]-oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one. Preferred examples of compounds of formula I as described herein are selected from 5-[5-(4-Hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one; (5S)-5-[5-(4-Hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one; (5R)-5-[5-(4-Hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one; rel-(3R,5R)-5-[5-[2-Hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin- 2-yl]-3-methoxy-piperidin-2-one or rel-(3S,5R)-5-[5-[2-hydroxy-6-methyl-4- (trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin-2-yl]-3-methoxy-piperidin-2-one; rel-(3S,5R)-5-[5-[2-Hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin- 2-yl]-3-methoxy-piperidin-2-one or rel-(3R,5R)-5-[5-[2-hydroxy-6-methyl-4- (trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin-2-yl]-3-methoxy-piperidin-2-one; (5S)-5-[5-(4-Hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2- yl]piperidin-2-one; (5R)-5-[5-(4-Hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2- yl]piperidin-2-one; and pharmaceutically acceptable salts thereof. More preferred examples of compounds of formula 1 as described herein are selected from 5-[5-(4-Hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one; (5S)-5-[5-(4-Hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one; (5R)-5-[5-(4-Hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one; (5S)-5-[5-(4-Hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2- yl]piperidin-2-one; (5R)-5-[5-(4-Hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2- yl]piperidin-2-one; and pharmaceutically acceptable salts thereof. Another embodiment of the invention provides a pharmaceutical composition or medicament containing a compound of the invention and a therapeutically inert carrier, diluent or excipient, as well as a method of using the compounds of the invention to prepare such composition and medicament. In one example, the compound of formula I may be formulated by mixing at ambient temperature at the appropriate pH, and at the desired degree of purity, with physiologically acceptable carriers, i.e., carriers that are non-toxic to recipients at the dosages and concentrations employed into a galenical administration form. The pH of the formulation depends mainly on the particular use and the concentration of compound, but preferably ranges anywhere from about 3 to about 8. In one example, a compound of formula I is formulated in an acetate buffer, at pH 5. In another embodiment, the compound of formula I is sterile. The compound may be stored, for example, as a solid or amorphous composition, as a lyophilized formulation or as an aqueous solution. Compositions are formulated, dosed, and administered in a fashion consistent with good medical practice. Factors for consideration in this context include the particular disorder being treated, the particular mammal being treated, the clinical condition of the individual patient, the cause of the disorder, the site of delivery of the agent, the method of administration, the scheduling of administration, and other factors known to medical practitioners. The compounds of the invention may be administered by any suitable means, including oral, topical (including buccal and sublingual), rectal, vaginal, transdermal, parenteral, subcutaneous, intraperitoneal, intrapulmonary, intradermal, intrathecal and epidural and intranasal, and, if desired for local treatment, intralesional administration. Parenteral infusions include intramuscular, intravenous, intraarterial, intraperitoneal, or subcutaneous administration. The compounds of the present invention may be administered in any convenient administrative form, e.g., tablets, powders, capsules, solutions, dispersions, suspensions, syrups, sprays, suppositories, gels, emulsions, patches, etc. Such compositions may contain components conventional in pharmaceutical preparations, e.g., diluents, carriers, pH modifiers, sweeteners, bulking agents, and further active agents. A typical formulation is prepared by mixing a compound of the present invention and a carrier or excipient. Suitable carriers and excipients are well known to those skilled in the art and are described in detail in, e.g., Ansel, Howard C., et al., Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems. Philadelphia: Lippincott, Williams & Wilkins, 2004; Gennaro, Alfonso R., et al. Remington: The Science and Practice of Pharmacy. Philadelphia: Lippincott, Williams & Wilkins, 2000; and Rowe, Raymond C. Handbook of Pharmaceutical Excipients. Chicago, Pharmaceutical Press, 2005. The formulations may also include one or more buffers, stabilizing agents, surfactants, wetting agents, lubricating agents, emulsifiers, suspending agents, preservatives, antioxidants, opaquing agents, glidants, processing aids, colorants, sweeteners, perfuming agents, flavoring agents, diluents and other known additives to provide an elegant presentation of the drug (i.e., a compound of the present invention or pharmaceutical composition thereof) or aid in the manufacturing of the pharmaceutical product (i.e., medicament). The compounds of formula I and their pharmaceutically acceptable salts can be processed with pharmaceutically inert, inorganic or organic adjuvants for the production of tablets, coated tablets, dragées,hard gelatin capsules, injection solutions or topical formulations Lactose, corn starch or derivatives thereof, talc, stearic acid or its salts etc. can be used, for example, as such adjuvants for tablets, dragées and hard gelatin capsules. Suitable adjuvants for soft gelatin capsules, are, for example, vegetable oils, waxes, fats, semi-solid substances and liquid polyols, etc. Suitable adjuvants for the production of solutions and syrups are, for example, water, polyols, saccharose, invert sugar, glucose, etc. Suitable adjuvants for injection solutions are, for example, water, alcohols, polyols, glycerol, vegetable oils, etc. Suitable adjuvants for suppositories are, for example, natural or hardened oils, waxes, fats, semi-solid or liquid polyols, etc. Suitable adjuvants for topical ocular formulations are, for example, cyclodextrins, mannitol or many other carriers and excipients known in the art. Moreover, the pharmaceutical preparations can contain preservatives, solubilizers, viscosity-increasing substances, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavorants, salts for varying the osmotic pressure, buffers, masking agents or antioxidants. They can also contain still other therapeutically valuable substances. The dosage can vary in wide limits and will, of course, be fitted to the individual requirements in each particular case. In general, in the case of oral administration a daily dosage of about 0.1 mg to 20 mg per kg body weight, preferably about 0.5 mg to 4 mg per kg body weight (e.g. about 300 mg per person), divided into preferably 1-3 individual doses, which can consist, for example, of the same amounts, should it be appropriate. In the case of topical administration, the formulation can contain 0.001% to 15% by weight of medicament and the required dose, which can be between 0.1 and 25 mg in can be administered either by single dose per day or per week, or by multiple doses (2 to 4) per day, or by multiple doses per week It will, however, be clear that the upper or lower limit given herein can be exceeded when this is shown to be indicated. An embodiment of the present invention is a compound according to formula I as described herein for use as a therapeutically active substance. An embodiment of the present invention is a compound according to formula I as described herein for use in the treatment or prevention of a disease, disorder or condition, wherein the disease, disorder or condition is responsive to NLRP3 inhibition. An embodiment of the present invention is a compound according to formula I as described herein for the treatment or prophylaxis of a disease, disorder or condition, wherein the disorder or condition is responsive to NLRP3 inhibition. As used herein, the term “NLRP3 inhibition” refers to the complete or partial reduction in the level of activity of NLRP3 and includes, for example, the inhibition of active NLRP3 and / or the inhibition of activation of NLRP3. There is evidence for a role of NLRP3-induced IL-1 and IL-18 in the inflammatory responses occurring in connection with, or as a result of, a multitude of different disorders (Menu et al., Clinical and Experimental Immunology, 166: 1-15, 2011; Strowig et al., Nature, 481: 278- 286, 2012). In one embodiment, the disease, disorder or condition is selected from: (i) inflammation; (ii) an auto-immune disease; (iii) cancer; (iv) an infection; (v) a central nervous system disease; (vi) a metabolic disease; (vii) a cardiovascular disease; (viii) a respiratory disease; (ix) a liver disease; (x) a renal disease; (xi) an ocular disease; (xii) a skin disease; (xiii) a lymphatic condition; (xiv) a psychological disorder; (xv) graft versus host disease; (xvi) allodynia; (xvii) a condition associated with diabetes; and (xviii) any disease where an individual has been determined to carry a germline or somatic non-silent mutation in NLRP3 In another embodiment, the disease, disorder or condition is selected from: (i) cancer; (ii) an infection; (iii) a central nervous system disease; (iv) a cardiovascular disease; (v) a liver disease; (vi) an ocular disease; and (vii) a skin disease. In a further typical embodiment of the invention, the disease, disorder or condition is inflammation. Examples of inflammation that may be treated or prevented include inflammatory responses occurring in connection with, or as a result of: (i) a skin condition such as contact hypersensitivity, bullous pemphigoid, sunburn, psoriasis, atopical dermatitis, contact dermatitis, allergic contact dermatitis, seborrhoetic dermatitis, lichen planus, scleroderma, pemphigus, epidermolysis bullosa, urticaria, erythemas, or alopecia; (ii) a joint condition such as osteoarthritis, systemic juvenile idiopathic arthritis, adult-onset Still’s disease, relapsing polychondritis, rheumatoid arthritis, juvenile chronic arthritis, gout, or a seronegative spondyloarthropathy (e.g. ankylosing spondylitis, psoriatic arthritis or Reiter’s disease); (iii) a muscular condition such as polymyositis or myasthenia gravis; (iv) a gastrointestinal tract condition such as inflammatory bowel disease (including Crohn’s disease and ulcerative colitis), colitis, gastric ulcer, Coeliac disease, proctitis, pancreatitis, eosinopilic gastro-enteritis, mastocytosis, antiphospholipid syndrome, or a food-related allergy which may have effects remote from the gut (e.g., migraine, rhinitis or eczema); (v) a respiratory system condition such as chronic obstructive pulmonary disease (COPD), asthma (including eosinophilic, bronchial, allergic, intrinsic, extrinsic or dust asthma, and particularly chronic or inveterate asthma, such as late asthma and airways hyper-responsiveness), bronchitis, rhinitis (including acute rhinitis, allergic rhinitis, atrophic rhinitis, chronic rhinitis, rhinitis caseosa, hypertrophic rhinitis, rhinitis pumlenta, rhinitis sicca, rhinitis medicamentosa, membranous rhinitis, seasonal rhinitis e.g. hay fever, and vasomotor rhinitis), sinusitis, idiopathic pulmonary fibrosis (IPF), sarcoidosis, farmer’s lung, silicosis, asbestosis, volcanic ash induced inflammation, adult respiratory distress syndrome, hypersensitivity pneumonitis, or idiopathic interstitial pneumonia; (vi) a vascular condition such as atherosclerosis, Behcet’s disease, vasculitides, or Wegener’s granulomatosis; (vii) an autoimmune condition such as systemic lupus erythematosus, Sjögren’s syndrome, systemic sclerosis, Hashimoto’s thyroiditis, type I diabetes, idiopathic thrombocytopenia purpura, or Graves disease; (viii) an ocular condition such as uveitis, allergic conjunctivitis, or vernal conjunctivitis; (ix) a nervous condition such as multiple sclerosis or encephalomyelitis; (x) an infection or infection-related condition, such as Acquired Immunodeficiency Syndrome (AIDS), acute or chronic bacterial infection, acute or chronic parasitic infection, acute or chronic viral infection, acute or chronic fungal infection, meningitis, hepatitis (A, B or C, or other viral hepatitis), peritonitis, pneumonia, epiglottitis, malaria, dengue hemorrhagic fever, leishmaniasis, streptococcal myositis, mycobacterium tuberculosis (including mycobacterium tuberculosis and HIV co-infection), mycobacterium avium intracellulare, pneumocystis carinii pneumonia, orchitis / epidydimitis, legionella, Lyme disease, influenza A, Epstein-Barr virus infection, viral encephalitis / aseptic meningitis, or pelvic inflammatory disease; (xi) a renal condition such as mesangial proliferative glomerulonephritis, nephrotic syndrome, nephritis, glomerular nephritis, obesity related glomerulopathy, acute renal failure, acute kidney injury, uremia, nephritic syndrome, kidney fibrosis including chronic crystal nephropathy, or renal hypertension; (xii) a lymphatic condition such as Castleman’s disease; (xiii) a condition of, or involving, the immune system, such as hyper IgE syndrome, lepromatous leprosy, familial hemophagocytic lymphohistiocytosis, or graft versus host disease; (xiv) a hepatic condition such as chronic active hepatitis, non-alcoholic steatohepatitis (NASH), alcohol-induced hepatitis, non-alcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease (AFLD), alcoholic steatohepatitis (ASH), primary biliary cirrhosis, fulminant hepatitis, liver fibrosis, or liver failure; (xv) a cancer, including those cancers listed above; (xvi) a burn, wound, trauma, haemorrhage or stroke; (xvii) radiation exposure; (xviii) a metabolic disease such as type 2 diabetes (T2D), atherosclerosis, obesity, gout or pseudo-gout; and / or (xix) pain such as inflammatory hyperalgesia, pelvic pain, allodynia, neuropathic pain, or cancer-induced bone pain. An embodiment of the present invention is a compound according to formula I as described herein for the treatment or prophylaxis of a disease, disorder or condition selected from: inflammation; an auto-immune disease; cancer; an infection; a central nervous system disease; a metabolic disease; a cardiovascular disease; a respiratory disease; a liver disease; a renal disease; an ocular disease; a skin disease; a lymphatic condition; a psychological disorder; graft versus host disease; allodynia; a condition associated with diabetes; and any disease where an individual has been determined to carry a germline or somatic non- silent mutation in NLRP3. An embodiment of the present invention is the use of a compound according to formula I as described herein in the treatment or prophylaxis of a disease, disorder or condition, wherein the disease, disorder or condition is responsive to NLRP3 inhibition. An embodiment of the present invention is the use of a compound according to formula I as described herein in the treatment or prophylaxis of a disease, disorder or condition selected from Alzheimer’s disease and Parkinson’s disease. An embodiment of the present invention is the use of a compound according to formula I as described herein in the treatment or prophylaxis of a disease, disorder or condition selected from Multiple Sclerosis (MS) and Amyotrophic lateral sclerosis (ALS). An embodiment of the present invention is the use a compound according to formula I as described herein for use in the treatment or prophylaxis of a disease, disorder or condition selected from Asthma and COPD. An embodiment of the present invention is the use a compound according to formula I as described herein for use in the treatment or prophylaxis of a disease, disorder or condition selected from Cryopyrin-associated periodic syndromes. An embodiment of the present invention is a compound according to formula I as described herein for the treatment or prophylaxis of a disease, disorder or condition selected from Alzheimer’s disease and Parkinson’s disease. An embodiment of the present invention is a compound according to formula I as described herein for the treatment or prophylaxis of a disease, disorder or condition selected from Multiple Sclerosis (MS) and Amyotrophic lateral sclerosis (ALS). An embodiment of the present invention is a compound according to formula I as described herein for the treatment or prophylaxis of a disease, disorder or condition selected from Asthma and COPD. An embodiment of the present invention is a compound according to formula I as described herein for the treatment or prophylaxis of a disease, disorder or condition selected from Cryopyrin-associated periodic syndromes. An embodiment of the present invention is the use of a compound according to formula I as described herein for preparation of a medicament for the treatment or prophylaxis of a disease, disorder or condition selected from Alzheimer’s disease and Parkinson’s disease. An embodiment of the present invention is the use of a compound according to formula I as described herein for preparation of a medicament for the treatment or prophylaxis of a disease, disorder or condition selected from Multiple Sclerosis (MS) and Amyotrophic lateral sclerosis (ALS). An embodiment of the present invention is the use of a compound according to formula I as described herein for the preparation of a medicament for the treatment or prophylaxis of a disease, disorder or condition selected from Asthma and COPD. An embodiment of the present invention is the use of a compound according to formula I as described herein for the preparation of a medicament for the treatment or prophylaxis of a disease, disorder or condition selected from Cryopyrin-associated periodic syndromes. An embodiment of the present invention is a method of treatment or prophylaxis of a disease, disorder or condition selected from Alzheimer’s disease and Parkinson’s disease, which method comprises administering an effective amount of a compound according to formula I as described herein. An embodiment of the present invention is a method of treatment or prophylaxis of a disease, disorder or condition selected from Multiple Sclerosis (MS) and Amyotrophic lateral sclerosis (ALS), which method comprises administering an effective amount of a compound according to formula I as described herein. An embodiment of the present invention is a method of treatment or prophylaxis of a disease, disorder or condition selected from Asthma and COPD, which method comprises administering an effective amount of a compound according to formula I as described herein. An embodiment of the present invention is a method of treatment or prophylaxis of a disease, disorder or condition selected from Cryopyrin-associated periodic syndromes, which method comprises administering an effective amount of a compound according to formula I as described herein. An embodiment of the present invention relates to a method of inhibiting NLRP3, which method comprises administering an effective amount of a compound according to formula I as described herein. Also an embodiment of the present invention are compounds of formula I as described herein, when manufactured according to any one of the described processes. An embodiment of the present invention is a pharmaceutical composition comprising a compound according to formula I as described herein and a therapeutically inert carrier. Assay Procedures NLRP3 and Pyroptosis It is well established that the activation of NLRP3 leads to cell pyroptosis and this feature plays an important part in the manifestation of clinical disease (Yan-gang Liu et al., Cell Death & Disease, 2017, 8(2), e2579; Alexander Wree et al., Hepatology, 2014, 59(3), 898-910; Alex Baldwin et al., Journal of Medicinal Chemistry, 2016, 59(5), 1691-1710; Ema Ozaki et al., Journal of Inflammation Research, 2015, 8, 15-27; Zhen Xie & Gang Zhao, Neuroimmunology Neuroinflammation, 2014, 1(2), 60-65; Mattia Cocco et al., Journal of Medicinal Chemistry, 2014, 57(24), 10366-10382; T. Satoh et al., Cell Death & Disease, 2013, 4, e644). Therefore, it is anticipated that inhibitors of NLRP3 will block pyroptosis, as well as the release of pro- inflammatory cytokines (e.g. IL-1β) from the cell. THP-1 Cells: Culture and Preparation THP-1 cells (ATCC # TIB-202) were grown in RPMI containing L-glutamine (Gibco #11835) supplemented with 1mM sodium pyruvate (Sigma # S8636) and penicillin (100units / ml) / streptomycin (0.1mg / ml) (Sigma # P4333) in 10% Fetal Bovine Serum (FBS) (Sigma # F0804). The cells were routinely passaged and grown to confluency (~106cells / ml). On the day of the experiment, THP-1 cells were harvested and resuspended into RPMI medium (without FBS). The cells were then counted and viability (>90%) checked by Trypan blue (Sigma # T8154). Appropriate dilutions were made to give a concentration of 625,000cells / ml. To this diluted cell solution was added LPS (Sigma # L4524) to give a 1µg / ml Final Assay Concentration (FAC). 40µl of the final preparation was aliquoted into each well of a 96-well plate. The plate thus prepared was used for compound screening. THP-1 Cells Pyroptosis Assay The following method step-by-step assay was followed for compound screening. Seed THP-1 cells (25,000cells / well) containing 1.0µg / ml LPS in 40µl of RPMI medium (without FBS) in 96-well, black walled, clear bottom cell culture plates coated with poly-D-lysine (VWR # 734-0317) Add 5µl compound (8 points half-log dilution, with 10µM top dose) or vehicle (DMSO 0.1% FAC) to the appropriate wells Incubate for 3 hours at 37 °C, 5% CO2 Add 5µl nigericin (Sigma # N7143) (FAC 5µM) to all wells Incubate for 1hr at 37°C, 5% CO2 At the end of the incubation period, spin plates at 300xg for 3mins and remove supernatant Then add 50µl of resazurin (Sigma # R7017) (FAC 100 µM resazurin in RPMI medium without FBS) and incubate plates for a further 1-2 hours at 37 °C and 5% CO2 Plates were read in an Envision reader at Ex 560nm and Em 590nm IC50 data is fitted to a non-linear regression equation (log inhibitor vs response-variable slope 4- parameters) The results of the pyroptosis assay are summarised in Table 1 below as THP IC50. Human Whole Blood IL-1β Release Assay For systemic delivery, the ability to inhibit NLRP3 when the compounds are present within the bloodstream is of great importance. For this reason, the NLRP3 inhibitory activity of a number of compounds in human whole blood was investigated in accordance with the following protocol. Human whole blood in Li-heparin tubes was obtained from healthy donors from a volunteer donor panel. Plate out 80µl of whole blood containing 1µg / ml of LPS in 96-well, clear bottom cell culture plate (Corning # 3585) Add 10µl compound (8 points half-log dilution with 10µM top dose) or vehicle (DMSO 0.1% FAC) to the appropriate wells Incubate for 3 hours at 37 °C, 5% CO2Add 10µl nigericin (Sigma # N7143) (10µM FAC) to all wells Incubate for 1hr at 37°C, 5% CO2At the end of the incubation period, spin plates at 300xg for 5mins to pellet cells and remove 20µl of supernatant and add to 96-well v-bottom plates for IL-1β analysis (note: these plates containing the supernatants can be stored at -80°C to be analysed at a later date) IL-1β was measured according to the manufacturer protocol (Perkin Elmer-AlphaLisa IL-1 Kit AL220F-5000) IC50 data is fitted to a non-linear regression equation (log inhibitor vs response-variable slope 4- parameters) The results of the human whole blood assay are summarised in Table 1 below as HWB IC50. Microsomal Stability: Incubations of test compounds at 1 µM in microsomes (0.5 mg / mL) plus cofactor NADPH are performed in 96 well plates at 37°C on a TECAN (Tecan Group Ltd, Switzerland) automated liquid handling system. After a 10 minutes pre-incubation step of the test compound with the microsomes, the enzymatic reaction is started by the addition of cofactors. At 1, 3, 6, 9, 15, 25, 35 and 45 minutes, aliquots of the incubations are removed and quenched with 1:3 (v / v) acetonitrile containing internal standard. Samples are then cooled and centrifuged before analysis of the supernatant by LC-MS / MS 2. Metabolic Stability in Hepatocytes: Assay descriptions: Biological materials. Cryopreserved hepatocytes [mouse, rat, rabbit, monkey and human (male and female; mixed)] are obtained. Viability of hepatocytes after reconstitution is at least 80% throughout the study. Ready-to-use rat / human HepatoPac® cultures [long-term hepatocyte co- cultures; pooled (n=5 for male and n=5 for female for human)] with stromal mouse fibroblasts (negative control; pooled) with the plates for incubations, application medium and maintenance medium are acquired. Metabolism by suspended hepatocytes. Primary pooled cryopreserved hepatocytes are reconstituted in pre-warmed William’s E media containing 10% FCS, 0.05 mg / mL streptomycin and 50 U / mL penicillin and 0.4 mM L-glutamine; and 0.01 mg / mL gentamicin, 0.048 mg / mL hydrocortisone and 0.004 mg / mL insulin, to a final suspension density of 1×106 cells / mL. The incubation was performed fully automatically with Liquid Handling System (Tecan) equipped with a CO2 incubator with an orbital shaker. After the addition of a test compound at e.g.1 µM to the wells (1×105 cells / well), the 96-well hepatocyte suspension culture plates are incubated in a 5% CO2 at 37°C. Samples are quenched by addition of acetonitrile (including an internal standard) to the incubation well at the designated time points up to 2 h. Metabolism by HepatoPac®. Incubations for a test article (at e.g. 1 µM, 0.1% v / v DMSO) as conducted in suspension assays are performed in 96-well plates containing either a co-culture of adherent hepatocytes with mouse fibroblast control cells or control cells alone (5% CO2 atmosphere and 37°C). The incubation media in human HepatoPac® is identical with that in suspended hepatocytes. At defined time points (2, 18, 26, 48, 72 and 96 h), whole wells are quenched with ice-cold acetonitrile containing an internal standard. Samples are then centrifuged appropriately and the supernatant analyzed by LC-MS / MS. The incubation is conducted in n=1 or 2. hERG screening assay In the drug development process of small molecules, one of the most frequent adverse side effects, leading to the failure of drugs, is the cardiac arrhythmias. Such failure is often related to the capacity of the drug to inhibit the human ether-à-go-go-related gene (hERG) cardiac potassium channel. Having no or low inhibition of the hERG cardiac potassium channel is therefore considered as beneficial. Cells The CHO crelox hERG cell line (ATCC reference Nr. PTA-6812, female Chinese hamster cells) was generated and validated at Roche. Ready-to-use frozen instant CHO-hERG cells were cryopreserved at Evotec (Germany) and used directly in the experiments. Experimental solutions The extracellular solution contains (in mM): NaCl 150; KCl 4; CaCl21; MgCl21; HEPES 10; pH 7.2-7.4 with NaOH, osmolarity 290-330 mOsm. The internal solution contains (in mM): KCl, 10; KF, 100; NaCl, 10; HEPES, 10; EGTA, 20; pH = 7.0-7.4 with KOH, osmolarity 260- 300 mOsm. Electrophysiology The effects of a compound on hERG K+-currents parameters will be evaluated at 2 concentrations in at least 4 cells. The hERG test is performed using automated patch clamp system SynchroPatch® 384 (Nanion Technologies GmbH, Germany). K+ currents are measured with the patch-voltage- clamp technique in the whole-cell configuration at 35-37°C. Cells were held at a resting voltage of -80 mV and they were stimulated by a voltage pattern shown in Figure 1 (pulse pattern used to elicit outward K+current at 35-37°C) to activate hERG channels and conduct outward IKhERG current, at a stimulation frequency of 0.1 Hz (6 bpm) Data analysis The amplitudes of IKhERG were recorded in each concentration of drug and they were compared to the vehicle control values (taken as 100%) to define fractional blocks. The concentration-response data were fitted with the following relationship: 100 ^ ^ C ^ ^ 1 ^ ^C / IC 50 ^hwhere C is the concentration, IC50is the concentration producing 50% block h is the Hill coefficient. Concentration-response curves were fitted by non-linear regression analysis using EworkBook suite (ID Business Solutions Ltd, UK). Data fit was done with the 4 Parameter Logistic Model (fit = (A+(B / (1+((x / C)^D)))), where A=0 and B=100). The results of the hERG assay are summarised in Table 2 below as hERG IC20. Transcellular P-gp Assay: The general assay uses transfected LLC-PK1 cells (porcine kidney epithelial cells) over- expressing human or mouse P-gp, cultured on 96 well semi-permeable filter membrane plates, where they form a polarized monolayer with tight junctions, and act as a barrier between the apical and basolateral compartment. P-gp is expressed in the apical-facing membrane of the monolayer. The tightness of the cell monolayer and functional activity of P-gp are confirmed by addition of a cell-impermeable marker, Lucifer yellow, and a reference P-gp substrate, edoxaban, respectively. Table 1: NLRP3 inhibitory activity THP-1 Human Example pyroptosis whole blood No. Assay IL-1β Assay IC50 (nM) IC50 (nM) 1 12.6 25.3 1A3.3 21.3 1B 4.4 14.1 2A 31.1 319.3 2B55.3 90.6 3A10.3 26.4 3B 9.7 20.1 4 62.9 293.5 5 9.4 84.2 6 29.2 76.6 6A 26.8 40.7 6B 31.9 38.1 7 18.9 16.2 8 9.3 16.0 9 32.2 27.5 9A 173.7 9B21.2 20.0 10 12.6 42.5 10A 22.5 33.1 10B 8.2 31.4 11 74.5 89.7 1217.7 73.8 The invention will now be illustrated by the following examples which have no limiting character. In case the preparative examples are obtained as a mixture of enantiomers or diastereoisomers, the pure enantiomers or diastereomers can be obtained by methods described herein or by methods known to those skilled in the art, such as e.g. chiral chromatography or crystallization. Experimental Methods Abbreviations ACN Acetonitrile Aq. Aqueous DBU 1,8-Diazabicyclo[5.4.0]undec-7-ene DCM Dichloromethane DEA Diethylamine DMF Dimethylformamide ESI Electrospray ionization EtOH Ethanol EtOAC Ethyl acetate eq Equivalent FA Formic acid h, hrs Hour(s) HPLC High-performance liquid chromatography LCMS Liquid chromatography–mass spectrometry LDA Lithium diisopropylamide MeCN Acetonitrile MeOH Methanol mins Minutes NBS N-Bromosuccinimide PPSE Polyphosphoric acid trimethylsilyl ester rt Room temperature tBME Methyl tert-butyl ether THF Tetrahydrofuran sat Saturated SFC Supercritical fluid chromatography Preparation of Intermediates Intermediate 1: 2-(4-Benzyloxy-6-methyl-indan-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Step A: 5-Bromo-6-methyl-indan-4-ol Sodium nitrite (800.0 mg, 11.6 mmol, 1.31 eq) in water (20 mL) was added dropwise to a stirred solution of 5-bromo-6-methyl-indan-4-amine (CAS # 2411531-03-6, 2.0 g, 8.85 mmol, 1.0 eq) in sulfuric acid (40.0 mL, 80.0 mmol, 9.04 eq) (2M in THF) at 0 °C. The reaction was stirred at 0 °C for 30 mins, then was allowed to warm to rt over ~30 mins. The reaction mixture was then added dropwise to a stirred solution of sulfuric acid (40.0 mL, 80.0 mmol, 9.04 eq) (2M in THF) at 50 °C and the reaction was stirred for a further 2.5 h. The reaction was allowed to cool to rt, then was diluted with water (200 mL) and EtOAc (200 mL). The layers were separated, and the aqueous layer was extracted with EtOAc (2 x 200 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo. The crude material was purified by column chromatography on silica gel (80 g cartridge, 0-5% EtOAc / isohexane) to afford the title compound (972.2 mg, 48% yield) as a light-yellow solid.1H NMR (500 MHz, DMSO) δ 9.13 (s, 1H), 6.70 (s, 1H), 2.80 (t, 2H), 2.76 (t, 2H), 2.27 (s, 3H), 1.97 (p, 2H). Step B: 4-Benzyloxy-5-bromo-6-methyl-indane Potassium carbonate (616.7 mg, 4.46 mmol, 2.03 eq) was added to a stirred solution of 5-bromo- 6-methyl-indan-4-ol (500.0 mg, 2.2 mmol, 1.0 eq) in acetone (20 mL) and the reaction was stirred at rt for 5 mins. Benzyl bromide (0.33 mL, 2.8 mmol, 1.27 eq) was then added dropwise and the reaction was stirred for 16 h. The reaction mixture was then heated to 45 °C and stirred for 4 d. The reaction mixture was diluted with EtOAc (50 mL) and water (50 mL) and the phases were separated. The aqueous layer was extracted with EtOAc (2 x 30 mL) and the combined organic layers were washed with water (50 mL) and brine (50 mL), dried (MgSO4) and concentrated in vacuo. The crude material was purified by column chromatography on silica gel (40 g, 0-20% EtOAc / heptane) to afford the title compound (510.1 mg, 69% yield) as a colourless oil.1H NMR (500 MHz, DMSO) δ 7.56 – 7.48 (m, 2H), 7.45 – 7.38 (m, 2H), 7.38 – 7.32 (m, 1H), 7.01 (s, 1H), 4.95 (s, 2H), 2.89 (t, 2H), 2.80 (t, 2H), 2.33 (s, 3H), 2.00 (p, 2H). Step C: 2-(4-Benzyloxy-6-methyl-indan-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane n-Butyl lithium (1.6 M in hexanes) (4.1 mL, 6.56 mmol, 1.6 eq) was added dropwise to a stirred solution of 4-benzyloxy-5-bromo-6-methyl-indane (1.3 g, 4.1 mmol, 1.0 eq) and 2-isopropoxy- 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.25 mL, 6.15 mmol, 1.5 eq) in THF (15 mL) at -78 °C and the reaction was stirred for 3 h. A further portion of n-butyl lithium (1.6 M in hexanes) (2.05 mL, 3.28 mmol, 0.8 eq) was added and the reaction was stirred for a further 1.5 h. The reaction was quenched by dropwise addition of NH4Cl (50 mL, sat aq) and the reaction was allowed to return to rt. The reaction mixture was diluted with EtOAc (50 mL) and the layers separated, the aqueous layer was extracted with EtOAc (2 x 50 mL). The combined organic layers were washed with brine (50 mL), dried (MgSO4) and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (120 g cartridge, 0-3% (EtOAc / isohexane)) to afford the title compound (619.1 mg, 39% yield) as an off white solid. LCMS m / z 365.0 [M+H]+ESI pos. Intermediate 2: 6-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydrobenzofuran-4-ol Step A: 1-(2-Benzyloxy-6-hydroxy-4-methyl-phenyl)ethanone To a solution of 1-(2,6-dihydroxy-4-methyl-phenyl)ethanone (CAS # 1634-34-0, 5.1 g, 30.7 mmol, 1.00 eq) in DMF (35 mL) was added potassium carbonate (4.38 g, 31.7 mmol, 1.03 eq) followed by benzyl bromide (5.46 g, 3.8 mL, 31.95 mmol, 1.04 eq). The reaction mixture was stirred at 60 °C for 16 h. The reaction mixture was cooled to room temperature and extracted with saturated aq. NH4Cl-solution and three times dichloromethane. The organic layers were washed with brine. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was adsorbed on ISOLUTE HM-N and purified by flash chromatography (silica gel, 220 g, gradient 5% to 20% ethyl acetate in heptane) to afford the title compound (4.94 g, 50% yield, 80% purity) as a yellow solid. LCMS: m / z 257.1 [M+H]+, ESI pos. Step B: 4-Benzyloxy-6-methyl-benzofuran-3-one To a solution of 1-(2-benzyloxy-6-hydroxy-4-methyl-phenyl)ethanone (2.81 g, 8.77 mmol, 1.00 eq, 80% purity) in tetrahydrofuran (40 mL) at -76 °C was added chlorotrimethylsilane (2.91 g, 3.4 mL, 26.79 mmol, 3.05 eq) followed by dropwise addition of 1 M lithium bis(trimethylsilyl)amide, solution in tetrahydrofuran / ethylbenzene (18.9 g, 22 mL, 22 mmol, 2.51 eq), keeping the internal temperature below -65 °C. After the addition was complete, the ice bath was removed and the reaction mixture was stirred at room temperature for 2.5 h. The reaction mixture was cooled to 0 °C and N-bromosuccinimide (1.90 g, 10.7 mmol, 1.22 eq) was added in three portions at 0 °C. Let stir at 0 °C for 20 min and at room temperature for 1 h and then added 1 M aq. NaOH-solution (10 mL, 10 mmol, 1.14 eq) and stirred at rt for 1 h. Poured into ice cold 1 M HCl-solution and extracted with ethyl acetate. The aqueous layer was backextracted with ethyl acetate. The organic layers were washed with brine. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was adsorbed on ISOLUTE HM-N and purified by flash chromatography (silica gel, 80 g, gradient 0% to 20% ethyl acetate in heptane) to afford the title compound (1.63 g, 66% yield, 90% purity) as a yellow solid. LCMS: m / z 255.1 [M+H]+, ESI pos. Step C: 4-Benzyloxy-6-methyl-2,3-dihydrobenzofuran-3-ol To a partial solution of 4-benzyloxy-6-methyl-benzofuran-3-one (1.05 g, 3.71 mmol, 1.00 eq, 90% purity) in methanol (10 mL) and tetrahydrofuran (5 mL) was added sodium borohydride (422 mg, 11.2 mmol, 3.00 eq) in three portions at 0 °C. The reaction mixture was stirred at 0 °C for 3 h. The reaction mixture was quenched with water and then extracted three times with dichloromethane. The organic layers were washed with brine. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to afford the title compound (1.03 g, 87% yield, 80% purity) as a light brown oil, which was used without further purification. LCMS: m / z 239.1 [M- H2O+H]+, ESI pos. Step D: 6-Methyl-2,3-dihydrobenzofuran-4-ol An autoclave was charged with 4-benzyloxy-6-methyl-2,3-dihydrobenzofuran-3-ol (1.03 g, 3.21 mmol, 1.00 eq) and methanol (32 mL). Pd(OH)2 / C 20% Het 60-1 (103 mg, 0.06 mmol, 0.015 eq) was added under argon. The reactor was sealed, evacuated and heated to 40 °C before filled with hydrogen gas (reaction pressure of 5 bar was set). The reaction mixture was stirred at 40 °C for 18 h. After the reactor was vented carefully, the reaction mixture was filtered (Pall Acrodisc CR 25 mm Syringe Filter 0.45 µm) and rinsed with methanol. The filtrate was concentrated to afford the title compound (556 mg, 92% yield, 80% purity) as a brown oil, which was used without further purification. LCMS: m / z 151.0 [M+H]+, ESI pos. Step E: 4-Benzyloxy-6-methyl-2,3-dihydrobenzofuran To a solution of 6-methyl-2,3-dihydrobenzofuran-4-ol (393 mg, 2.09 mmol, 1.00 eq, 80% purity) in acetonitrile (4.4 mL) was added potassium carbonate (582 mg, 4.21 mmol, 2.01 eq) followed by benzyl bromide (546 mg, 0.38 mL, 3.20 mmol, 1.53 eq). The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was extracted with ethyl acetate and water. The aqueous layer was backextracted with ethyl acetate. The organic layers were washed with water and brine. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was adsorbed on ISOLUTE HM-N and purified by flash chromatography (silica gel, gradient 0% to 5% ethyl acetate in heptane) to afford the title compound (379 mg, 60% yield, 80% purity) as a colorless oil. LCMS: m / z 241.1 [M+H]+, ESI pos. Step F: 4-Benzyloxy-5-bromo-6-methyl-2,3-dihydrobenzofuran To a solution of 4-benzyloxy-6-methyl-2,3-dihydrobenzofuran (377 mg, 1.26 mmol, 1.00 eq, 80% purity) in dichloromethane (14 mL) was added portionwise N-bromosuccinimide (294 mg, 1.65 mmol, 1.32 eq) at 0 °C. The reaction mixture was stirred at 0 °C for 5.5 h. The reaction mixture was quenched with saturated aq. NaHCO3-solution and extracted three times with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was adsorbed on ISOLUTE HM-N and purified by flash chromatography (silica gel, gradient 0% to 5% ethyl acetate in heptane). All fractions containing product were combined and concentrated in vacuo. The residue was adsorbed on ISOLUTE HM- N and purified a second time by flash chromatography (silica gel, gradient 0% to 50% dichloromethane in heptane) to afford the title compound (370 mg, 65% yield, 70% purity) as a colorless oil. LCMS: m / z 319.0; 321.0 (Br isotopes) [M+H]+, ESI pos. Step G: 2-(4-Benzyloxy-6-methyl-2,3-dihydrobenzofuran-5-yl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane To a solution of 4-benzyloxy-5-bromo-6-methyl-2,3-dihydrobenzofuran (490 mg, 1.07 mmol, 1.00 eq, 70% purity) and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (CAS # 61676- 62-8, 0.48 mL, 2.35 mmol, 2.19 eq) in tetrahydrofuran (6.4 mL) was added dropwise 1.6 M n- butyllithium, solution in hexanes (1.5 mL, 2.40 mmol, 2.23 eq) at -76 °C. Let stir at -76 °C for 3 h. The reaction mixture was warmed to -60 °C, quenched with saturated aq. NH4Cl-solution at - 60 °C, warmed to room temperature and then extracted with ethyl acetate. The aqueous layer was backextracted with ethyl acetate. The organic layers were washed with brine. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was adsorbed on ISOLUTE HM-N and purified by flash chromatography (silica gel, gradient 0% to 10% ethyl acetate in heptane) to afford the title compound (305 mg, 62% yield, 80% purity) as a colorless oil. LCMS: m / z 367.1 [M+H]+, ESI pos. Step H: 6-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydrobenzofuran-4-ol A solution of 2-(4-benzyloxy-6-methyl-2,3-dihydrobenzofuran-5-yl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane (300 mg, 0.66 mmol, 1.00 eq, 80% purity) in ethyl acetate (3.2 mL) and methanol (0.80 mL) was three times alternating evacuated and flushed with argon. Palladium on activated charcoal, 10% Pd basis (30 mg, 0.03 mmol, 0.04 eq) was added. The reaction flask was evacuated, flushed with argon, evacuated and flushed with hydrogen. The reaction mixture was stirred under hydrogen atmosphere (balloon) at room temperature for 2.5 h. The reaction mixture was filtered and rinsed well with ethyl acetate / methanol. The filtrate was concentrated in vacuo to afford the title compound (225 mg, 99% yield, 80% purity) as a colorless oil, which was used without further purification. LCMS: m / z 277.0 [M+H]+, ESI pos. Intermediate 3: 5-(5-Bromooxazolo[4,5-b]pyridin-2-yl)piperidin-2-one 6-Oxopiperidine-3-carboxylic acid (CAS # 22540-50-7, 41.0 mg, 0.29 mmol, 1.08 eq) and 2- amino-6-bromopyridin-3-ol (50.0 mg, 0.26 mmol, 1.0 eq) were added to polyphosphoric acid (1.0 mL) and the viscous mixture was heated at 100 °C and stirred for 48 h. The reaction mixture was spooned out and added to a separating funnel containing sat. aq. NaHCO3 (30 mL) resulting in vigorous bubbling, when bubbling had ceased, DCM (30 mL) was added and shaken. The separated aqueous layer was further extracted with DCM (2 x 30 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated to afford the title compound (38.0 mg, 43% yield) as a light brown solid. LCMS m / z 295.7 [M+H]+, ESI pos. Alternatively, Intermediate 3 was also synthesized using Eaton's Reagent as described below: To a mixture of 2-amino-6-bromo-pyridin-3-ol (CAS # 934758-27-7, 262 mg, 1.39 mmol, 1.00 eq) and 6-oxopiperidine-3-carboxylic acid (CAS # 22540-50-7, 219 mg, 1.53 mmol, 1.10 eq) was added Eaton's Reagent (CAS # 39394-84-8, 3.0 mL) at room temperature. The reaction mixture was stirred at 100 °C for 16 h. The reaction mixture was cooled to room temperature, added dropwise onto ~70 mL saturated aq. NaHCO3-solution (strong gas evolution) and extracted four times with a mixture of dichloromethane / methanol (9:1). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was adsorbed on ISOLUTE HM-N and purified by flash chromatography (silica gel, 25 g, gradient 0% to 5% methanol in dichloromethane) to afford the title compound (299 mg, 69% yield) as an off-white solid. LCMS: m / z 296.0 / 297.9 [M+H]+, ESI pos. Intermediate 4: 6-(Methoxymethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydrobenzofuran- 4-ol Step A: 2- Dibromo-4-(methoxymethyl)phenyl]ethanol To a solution of 1,3-dibromo-5-(methoxymethyl)benzene (171 g, 610 mmol, 1.00 eq, CAS# 1646314-10-4) in THF (750 mL) was added LDA (2.00 M, 366 mL, 1.20 eq) at -78 °C and stirring was continued for 30 mins. Afterwards, a solution of 1,3,2-dioxathiolane 2,2-dioxide (98.5 g, 794 mmol, 1.30 eq, CAS# 1072-53-3) in THF (750 mL) was added to the mixture at -78 °C. The mixture was warmed and stirred at 25 °C for 1 h. The reaction mixture was quenched by addition of aq. HCl (12.0 M, 170 mL) at 0 °C, and then diluted with water (500 mL) and extracted with EtOAc (500 mL x 3). The combined organic layers were washed with brine (500 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The crude was purified by column chromatography on silica gel (petroleum ether / ethyl acetate = 50 / 1 to 10 / 1) to yield the title compound (60.0 g, 30% yield) as a white solid. Step B: 4-Bromo-6-(methoxymethyl)-2,3-dihydrobenzofuran To a solution of 2-[2,6-dibromo-4-(methoxymethyl)phenyl]ethanol (60.0 g, 185 mmol, 1.00 eq) in dioxane (600 mL) was added t-BuOLi (44.4 g, 555 mmol, 50.0 mL, 3.00 eq) and CuI (3.53 g, 18.5 mmol, 0.10 eq) under N2atmosphere. The mixture was stirred at 100 °C for 5 h. The reaction mixture was quenched by addition water (1.00 L), and then diluted with ethyl acetate (500 mL) and extracted with ethyl acetate (500 mL x 3). The combined organic layers were washed with brine (500 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The title compound (50.0 g, crude) was obtained as a yellow oil and used without further purification in the next step. Step C: 6-(Methoxymethyl)-2,3-dihydrobenzofuran-4-ol To a solution of 4-bromo-6-(methoxymethyl)-2,3-dihydrobenzofuran (48.0 g, 197 mmol, 1.00 eq) in dioxane (250 mL) and H2O (250 mL) was added t-BuXphos (16.7 g, 39.4 mmol, 0.20 eq), Pd2 (dba)3(9.04 g, 9.87 mmol, 0.05 eq) and KOH (33.2 g, 592 mmol, 3.00 eq). The mixture was stirred at 80 °C for 16 h under N2 atmosphere. The mixture was adjusted to pH =5 with aq. HCl (12 M), and then extracted with ethyl acetate (500 mL x 3). The combined organic layers were washed with brine (500 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The crude was purified by column chromatography on silica gel (petroleum ether / ethyl acetate = 50 / 1 to 5 / 1) to afford the title compound (26 g, 74% yield) as a white solid. Step D: 5-Bromo-6-(methoxymethyl)-2,3-dihydrobenzofuran-4-ol To a solution of 6-(methoxymethyl)-2,3-dihydrobenzofuran-4-ol (25.0 g, 138 mmol, 1.00 eq) in DCM (250 mL) was added NBS (22.2 g, 124 mmol, 0.90 eq) at 0 °C. The mixture was stirred at 0 °C for 5 h. The reaction mixture was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel (petroleum ether / ethyl acetate: 50 / 1 to 10 / 1) toyield the title compound (16.0 g, 45% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ [ppm]:6.56 (s, 1H), 5.72 (s, 1H), 4.63 (t, 2H), 4.44 (s, 2H), 3.43 (s, 3H), 3.22 (t, 2H). Step E: 4-Benzyloxy-5-bromo-6-(methoxymethyl)-2,3-dihydrobenzofuran To a solution of 5-bromo-6-(methoxymethyl)-2,3-dihydrobenzofuran-4-ol (15.0 g, 57.8 mmol, 1.00 eq) in MeCN (150 mL) was added BnBr (10.8 g, 63.6 mmol, 7.56 mL, 1.10 eq) and K2CO3 (16.0 g, 115 mmol, 2.00 eq). The mixture was stirred at 25 °C for 2 h. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was diluted with water (100 mL) and extracted with EtOAc (50 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The crude product was triturated with petroleum ether (50.0 mL) at 25 °C for 16 h. The title compound (10.0 g, 74% yield) was obtained as a white solid. LCMS: m / z 350.0 [M+H]+, ESI pos. Step F: 2-[4-Benzyloxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5-yl]- tetramethyl- 1,3,2-dioxaborolane To a solution of 4-benzyloxy-5-bromo-6-(methoxymethyl)-2,3-dihydrobenzofuran (1.5 g, 4.08 mmol, 1.00 eq) and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.19 g, 1.3 mL, 6.37 mmol, 1.56 eq) in tetrahydrofuran (15 mL) was added dropwise 1.6 M n-butyllithium, solution in hexane (4 mL, 6.4 mmol, 1.57 eq) at -76 °C and stirring was continued at -76 °C for 2.25 h. The reaction mixture was warmed to -60 °C, quenched with saturated aq. NH4Cl-solution (~10 mL) at -60 °C, warmed to room temperature and then extracted with ethyl acetate (~70 mL) and saturated aq. NH4Cl-solution (~10mL). The aqueous layer was backextracted with ethyl acetate (~70mL). The organic layers were washed with brine (~10mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography (silica gel, 25g, gradient 0% to 20% ethyl acetate in heptane) to afford the title compound (1.26 g, 74% yield) as colorless oil. LCMS: m / z 397.3 [M+H]+, ESI pos. Step F: 6-(Methoxymethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3- dihydrobenzofuran-4-ol A solution of 2-[4-benzyloxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5-yl]-4,4,5,5- tetramethyl-1,3,2-dioxaborolane (1.24 g, 2.98 mmol, 1.00 eq) in ethyl acetate (15 mL) and methanol (2.5 mL) was three times alternating evacuated and flushed with argon. Palladium on activated charcoal, 10% Pd basis (136 mg, 127.8 µmol, 0.043 eq) was added carefully. The reaction flask was evacuated, flushed with argon, evacuated and flushed with hydrogen. The reaction mixture was stirred under hydrogen atmosphere (balloon) at room temperature for 3 h. Afterwards, the reaction mixture was filtered and rinsed with ethyl acetate / methanol. The filtrate was concentrated in vacuo to afford the title compound (929 mg, 97% yield) as light brown solid. LCMS: m / z 307.2 [M+H]+, ESI pos. The compound was used without further purification. Preparation of Examples Example 1: 5-[5-(4-Hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one Step A: 5-[5-(4-Benzyloxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one A solution of 5-(5-bromooxazolo[4,5-b]pyridin-2-yl)piperidin-2-one Intermediate 3 (129.0 mg, 0.44 mmol, 1.0 eq), 2-(4-benzyloxy-6-methyl-indan-5-yl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane Intermediate 1 (175.0 mg, 0.48 mmol, 1.1 eq), and potassium carbonate (151.0 mg, 1.09 mmol, 2.51 eq) in 1,4-dioxane (3 mL) and water (0.5 mL) was sparged (bubbling N2 while sonicating) for 10 min. [1,1'-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (CAS # 72287-26-4, 17.0 mg, 0.02 mmol, 0.05 eq) was added and the reaction mixture was heated to 90 °C for 16 h. The crude mixture concentrated under reduced pressure, loaded onto silica and purified by column chromatography on silica gel (40 g, 0-100% [1:9 MeOH (0.7 M·NH3): DCM] / DCM) to afford the title compound (68.0 mg, 29% yield) as a light brown oil. LCMS m / z 454.2 [M+H]+, ESI pos. Step B: 5-[5-(4-Hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one To a stirred solution of 5-[5-(4-benzyloxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2- yl]piperidin-2-one (68.0 mg, 0.13 mmol, 1.0 eq) in ethanol (3 mL) was added Pd / C (Type 87) (15.0 mg, 0.01 mmol, 0.06 eq) and the mixture placed in a hydrogenation vessel under 1.5 bar of H2. After 3 h, additional Pd / C (Type 87) (18.0 mg, 0.01 mmol, 0.07 eq) was added and the reaction was placed under 2 bar of H2and stirred for 16 h. The reaction mixture was filtered through celite, the filter cake rinsed with EtOH (50 mL) and concentrated under reduced pressure to afford the title compound (39.0 mg, 81% yield) as a grey solid. LCMS m / z 364.2 [M+H]+, ESI pos. Example 1A and 1B: (5S)-5-[5-(4-hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5R)-5-[5-(4-hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one and (5R)-5-[5-(4-hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5S)-5-[5-(4-hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one 5-[5-(4-Hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one Example 1 (15 mg) was dissolved to 8 mg / mL in MeOH mixture, filtered and was then purified by chiral SFC on a Waters prep 100 with a PDA and a QDA detectors, 40 °C, 120 bar. The column was a Phenomenex C3, 5 µm, 21 mm X 250 mm; flow rate 65 mL / min of 40% MeOH (0.1% DEA), 70% CO2. The clean fractions were pooled, rinsed with methanol, and concentrated to dryness using a rotary evaporator. The residues were re-dissolved in methanol transferred into final vials and evaporated on a Biotage V10. The samples were then further dried in a vacuum oven at 30 °C / 5 mbar overnight then freeze dried to afford Enantiomer 1 and Enantiomer 2 both as off-white solids. Enantiomer 1 (Example 1A, 9.7 mg, 32% yield) was obtained as an off-white solid; ee: 84%. LCMS m / z 364.2 [M+H]+, ESI pos.1H NMR (500 MHz, MeOD) δ 8.09 (d, 1H), 7.41 (d, 1H), 6.72 (s, 1H), 3.84 – 3.76 (m, 2H), 3.70 – 3.61 (m, 1H), 2.90 (t, 2H), 2.85 (t, 2H), 2.59 – 2.52 (m, 2H), 2.50 – 2.42 (m, 1H), 2.39 – 2.28 (m, 1H), 2.09 (p, 2H), 2.05 (s, 3H). Enantiomer 2 (Example 1B, 9.8 mg, 31% yield)) was obtained as an off-white solid; ee: 93%. LCMS m / z 364.2 [M+H]+, ESI pos.1H NMR (500 MHz, MeOD) δ 8.09 (d, 1H), 7.41 (d, 1H), 6.72 (s, 1H), 3.84 – 3.77 (m, 2H), 3.71 – 3.61 (m, 1H), 2.90 (t, 2H), 2.85 (t, 2H), 2.58 – 2.51 (m, 2H), 2.50 – 2.43 (m, 1H), 2.38 – 2.29 (m, 1H), 2.09 (p, 2H), 2.05 (s, 3H). Example 2A and 2B: rel-(3R,5R)-5-[5-[2-Hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin-2- yl]-3-methoxy-piperidin-2-one or rel-(3S,5R)-5-[5-[2-hydroxy-6-methyl-4- (trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin-2-yl]-3-methoxy-piperidin-2-one and rel- (3S,5R)-5-[5-[2-hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin-2-yl]-3- methoxy-piperidin-2-one or rel-(3R,5R)-5-[5-[2-hydroxy-6-methyl-4- (trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin-2-yl]-3-methoxy-piperidin-2-one (rel) (rel)Step A: 4,5-Dimethoxy-2-methylene-5-oxopentanoic acid To a solution of methyl 2-methoxyacetate (CAS # 6290-49-9, 1.46 g, 14.0 mmol, 1.1 eq) in THF (15 mL) lithium hexamethyldisilazane (29.3 mL, 29.3 mmol, 2.3 eq) was slowly added dropwise at -70 °C and stirred at -70 °C for 0.5 h. Then a solution of 2-(bromomethyl)acrylic acid (CAS # 72707-66-5, 2.10 g, 12.7 mmol, 1.0 eq) in THF (4 mL) was slowly added at -70°C, then stirred at -70 °C for 1 hour. Upon reaction completion, the mixture was quenched with saturated NH4Cl (100 mL) at 0 °C, then adjusted the pH ~ 2 using 1 M HCl solution, extracted with ethyl acetate (3 x 50 mL). The combined organic phase was washed with brine (200 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure to give the title compound (2.30 g, 96% yield) as yellow oil and used directly into the next step without further purification. Step B: 5-Methoxy-1-(4-methoxybenzyl)-6-oxopiperidine-3-carboxylic acid To a solution of aforementioned 4,5-dimethoxy-2-methylene-5-oxopentanoic acid (2.30 g, 12.2 mmol, 1.0 eq) in methanol (45 mL) was added 4-aminomethyl-anisole (7.98 mL, 61.1 mmol, 5.0 eq). Then the mixture was stirred at 70 °C for 24 h. Upon reaction completion, the mixture was cooled to room temperature, diluted with water (150 mL) and the pH was adjusted to about 12 with NaOH (1M aq. solution). The aqueous phase was washed with EtOAc (2 x 100 mL), then the pH of the aqueous phase was adjusted to about pH = 2 with HCl (1 M aq. solution), and then extracted with ethyl acetate (3 x 100 mL). The combined organic phase was washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure (temperature of water bath under 30 °C). The crude was purified by reversed- phase flash (CombiFlash 0.1% NH3•H2O aqueous-ACN condition) and followed by lyophilization to afford the title compound (1.20 g, 46% yield) as a yellow gum.1H NMR (400 MHz, CD3OD) δ 7.22 (d, 2H), 6.87 (d, 2H), 4.75 - 4.53 (m, 1H), 4.52 - 4.28 (m, 1H), 3.94 - 3.79 (m, 1H), 3.79 - 3.75 (m, 3H), 3.56 - 3.49 (m, 3H), 3.44 - 3.34 (m, 2H), 2.91 - 2.64 (m, 1H), 2.58 - 2.15 (m, 1H), 2.13 - 1.77 (m, 1H). Step C: N-(6-Bromo-3-hydroxy-2-pyridyl)-5-methoxy-1-[(4-methoxyphenyl)methyl]-6-oxo- piperidine-3-carboxamide To a solution of aforementioned 5-methoxy-1-(4-methoxybenzyl)-6-oxopiperidine-3-carboxylic acid (1.20 g, 4.09 mmol, 1.0 eq) in DCM (24 mL) was added a solution of oxalyl dichloride (0.5 mL, 7.43 mmol, 1.82 eq) in DCM (5 mL) at 0 °C, then DMF (0.1 mL) was added, and stirring was continued at 0 °C for 0.5 h. Afterwards, a solution of 2-amino-6-bromopyridin-3-ol (CAS # 934758-27-7, 1.71 g, 9.04 mmol, 2.21 eq) and pyridine (0.6 mL, 7.43 mmol, 1.82 eq) in THF (5 mL) was added dropwise, then stirred at 20 °C for 4 h. Upon reaction completion, the mixture was diluted with water (100 mL), extracted with ethyl acetate (3 x 50 mL). The combined organic phase was washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by column silica gel column chromatography (petroleum ether: ethyl acetate = 1:0 to 0:1) to give the title compound (0.60 g, 32% yield) as a yellow gum. LCMS: m / z 466.0 [M+2+H]+, ESI pos. Step D: 5-(5-Bromooxazolo[4,5-b]pyridin-2-yl)-3-methoxypiperidin-2-one The solution of N-(6-bromo-3-hydroxy-2-pyridyl)-5-methoxy-1-[(4-methoxyphenyl)methyl]-6- oxo-piperidine-3-carboxamide (0.30 g, 0.65 mmol, 1.0 eq) in Eaton's reagent (1.5 mL, 0.65 mmol, 1.0 eq), was stirred at 110 °C for 1 h. Upon reaction completion, the mixture was cooled to room temperature, diluted with MeCN (50 mL), then adjusted the pH to about 7 with weakly basic resin, filtered and the filtrate was concentrated under reduced pressure. The crude was purified by reversed-phase flash (CombiFlash, aqueous-ACN condition) and followed by lyophilization to afford the title compound (0.110 g, 50% yield). LCMS: m / z 327.9 [M+2+H]+, ESI pos. Step E: rel-(3R,5R)-5-[5-[2-Hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin- 2-yl]-3-methoxy-piperidin-2-one or rel-(3S,5R)-5-[5-[2-hydroxy-6-methyl-4- (trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin-2-yl]-3-methoxy-piperidin-2-one and (3S,5R)- 5-[5-[2-hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin-2-yl]-3-methoxy- piperidin-2-one or rel-(3R,5R)-5-[5-[2-hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5- b]pyridin-2-yl]-3-methoxy-piperidin-2-one To a solution of 5-(5-bromooxazolo[4,5-b]pyridin-2-yl)-3-methoxypiperidin-2-one (0.100 g, 0.31 mmol, 1.0 eq) and 3-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5- (trifluoromethyl)phenol (CAS # 2557358-38-8, 0.129 g, 0.43 mmol, 1.4 eq), KF (0.089 g, 1.53 mmol, 5.0 eq) in 1,4-dioxane (3 mL) and water (0.5 mL) was added XPhos Pd G3 (0.052 g, 0.06 mmol, 0.2 eq), then stirred at 85 °C for 2 h under nitrogen atmosphere. Upon reaction completion, the mixture was cooled to room temperature. The crude was purified by reversed-phase flash (CombiFlash aqueous-ACN condition) and followed by lyophilization to afford a white solid. Then the above white solid was purified by preparative HPLC (Column: Waters xbridge 150*25mm 10um; Condition water (NH4HCO3)-MeCN; Begin B 21, End B 51; Gradient Time(min) 10100%B; Hold Time(min) 2; FlowRate(mL / min) 25) to yield the respective isomers. First eluting mixture of 2 Isomers with unknown configuration: (Example 2A, 8.41 mg, 6% yield) as a white solid. SFC: Rt1 = 1.131 min, Rt2 = 1.594 min. LCMS: m / z 422.1 [M+H]+, ESI pos.1H NMR (400 MHz, CD3OD) δ 8.18 (d, 1H), 7.49 (d, 1H), 7.09 (s, 1H), 7.03 (s, 1H), 4.09 - 3.98 (m, 1H), 3.87 - 3.72 (m, 3H), 3.53 (s, 3H), 2.90 - 2.78 (m, 1H), 2.40 - 2.25 (m, 1H), 2.13 (s, 3H). Second eluting mixture of 2 isomers with unknown configuration: (Example 2B, 12.3 mg, 8.6% yield) as a white solid. SFC: Rt1 = 1.433 min, Rt2 =1.572 min, LCMS: m / z 422.0 [M+H]+, ESI pos.1H NMR (400 MHz, CD3OD) δ 8.15 (d, 1H), 7.45 (d, 1H), 7.09 (s, 1H), 7.03 (s, 1H), 3.91 - 3.79 (m, 3H), 3.78 - 3.68 (m, 1H), 3.58 (s, 3H), 2.63 - 2.54 (m, 1H), 2.53 - 2.43 (m, 1H), 2.12 (s, 3H). Example 3A and 3B: (5R)-5-[5-(4-Hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2- yl]piperidin-2-one or (5S)-5-[5-(4-hydroxy-6-methyl-2,3-dihydrobenzofuran-5- yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one and (5S)-5-[5-(4-hydroxy-6-methyl-2,3- dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5R)-5-[5-(4- hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one Step A: 5-[5-(4-Hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2- yl]piperidin-2-one A mixture of 5-(5-bromooxazolo[4,5-b]pyridin-2-yl)piperidin-2-one Intermediate 3 (135 mg, 0.43 mmol, 1.00 eq), 6-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3- dihydrobenzofuran-4-ol Intermediate 2 (229 mg, 0.66 mmol, 1.53 eq, 80% purity), potassium carbonate (263 mg, 1.90 mmol, 4.39 eq) and1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (53 mg, 0.06 mmol, 0.15 eq) in 1,4-dioxane (2.8 mL) and water (1.4 mL) was flushed with argon and stirred at 90 °C for 2 h. The reaction mixture was cooled to room temperature and extracted with a mixture of dichloromethane / methanol (19:1) and half-saturated aq. NH4Cl-solution. The organic layer was washed with water and brine. The aqueous layers were back-extracted twice with a mixture of dichloromethane / methanol (19:1). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was adsorbed on ISOLUTE HM-N and purified by flash chromatography (silica gel, 12 g, gradient 0% to 5% methanol in dichloromethane) to afford the title compound (142 mg, 76% yield, 85% purity) as a light brown solid. LCMS: m / z 366.1 [M+H]+, ESI pos. Step [5-(4-Hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2- yl]piperidin-2-one or 5-[5-(4-hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5- b]pyridin-2-yl]piperidin-2-one and 5-[5-(4-hydroxy-6-methyl-2,3-dihydrobenzofuran-5- yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or -5-[5-(4-hydroxy-6-methyl-2,3- dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one Chiral separation by SFC (column chiral OJ-H, eluent B: 25% methanol) of 5-[5-(4-hydroxy-6- methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one (Example 3, step A) (142 mg, 0.33 mmol, 1.00 eq, 85% purity) to afford the two enantiomers Example 3A (first eluting, Rt = 2.64 minutes) (47 mg, 37% yield) as an off-white solid; LCMS: m / z 366.1 [M+H]+, ESI pos and Example 3B (second eluting, Rt = 2.85 minutes) (55 mg, 43% yield) as an off-white solid; LCMS: m / z 366.1 [M+H]+, ESI pos. Example 4 5-Hydroxy-5-[5-[2-hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin-2- yl]piperidin-2-one Step A: 5-(5-Bromooxazolo[4,5-b]pyridin-2-yl)-5-hydroxy-piperidin-2-one To a solution of 5-(5-bromooxazolo[4,5-b]pyridin-2-yl)piperidin-2-one Intermediate 3 (0.300 g, 1.01 mmol, 1.0 eq) in THF (6 mL) was added LiHMDS (2.53 mL, 2.53 mmol, 2.5 eq) at -70°C under N2 and stirred for 0.5 h. Then a solution of 3-phenyl-2-(phenylsulfonyl)-1,2-oxaziridine (CAS # 63160-13-4, 0.397 g, 1.52 mmol, 1.5 eq) in THF (3 mL) was added dropwise and stirring was continued at -70 °C for 1 h. The reaction was quenched by addition of saturated NH4Cl (80 mL) and extracted with EtOAc (2 x 30 mL). Afterwards, the aqueous phase was lyophilized to afford a yellow solid and slurried with a mixture of EtOAc (40 mL) and MeOH (10 mL), filtered and the filtrate was concentrated under reduced pressure to give the crude product which was purified by prep-HPLC (Column: Phenomenex luna C18150 * 25mm * 10um; Condition: water (FA)-MeCN; Begin B 12; End B 42; Gradient Time(min) 9 100%B; Hold Time(min) 2; FlowRate(ml / min) 25) to afford the title compound (17.0 mg, 9% yield) as a white solid. LCMS: m / z 311.9 [M+2+H]+, ESI pos. Step B: 5-Hydroxy-5-[5-[2-hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin- 2-yl]piperidin-2-one To a solution of 3-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)- phenol (CAS # 2557358-38-8, 21.8 mg, 0.07 mmol, 1.5 eq), 5-(5-bromooxazolo[4,5-b]pyridin-2- yl)-5-hydroxy-piperidin-2-one (15.0 mg, 0.05 mmol, 1.0 eq), K3PO4(20.38 mg, 0.1 mmol, 2.0 eq) in 1,4-dioxane (1 mL) / water (0.2 mL) was added XPhos Pd G3 (4.07 mg, 0.0 mmol, 0.1 eq) and stirred for 2 h at 60 °C under N2. The mixture was cooled to 25 °C and the crude product was purified by reversed phase flash (CombiFlash 0.1%NH3·H2O water -MeCN condition) to yield the title compound (4.01 mg, 20% yield) as a white solid. LCMS: m / z 408.2 [M+H]+, ESI pos. Example 5: 1-(2-Hydroxyethyl)-5-[5-[2-hydroxy-6-methyl-4-(trifluoromethyl)phenyl]-oxazolo[4,5- b]pyridin-2-yl]piperidin-2-one Step A: Methyl 1-(2-hydroxyethyl)-6-oxo-pyridine-3-carboxylate To a suspension of methyl 6-oxo-1H-pyridine-3-carboxylate (CAS # 66171-50-4, 1.0 g, 6.53 mmol, 1.0 eq) in N,N-dimethylformamide (8.57 mL) was added cesium carbonate (4.97 g, 15.26 mmol, 2.3 eq) followed by the addition of 2-iodoethanol (2.26 g, 1.03 mL, 13.16 mmol, 2.0 eq). The reaction mixture was stirred at 90°C for 16 hours and left then standing at room temperature for 16 hours. After completion of the reaction, the mixture was extracted with water and tBME (100 mL). The aqueous layer was back-extracted with tBME (100 mL). The combined organic layers were washed three times with brine (50 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The crude was purified by flash chromatography on silica gel (DCM / MeOH, gradient 0-10% MeOH) to afford the title compound (320 mg, 24% yield) as a white solid. LCMS m / z: 198.0 [M+H]+, ESI pos. Step B: Methyl 1-(2-hydroxyethyl)-6-oxo-piperidine-3-carboxylate A forementioned methyl 1-(2-hydroxyethyl)-6-oxo-pyridine-3-carboxylate (210 mg, 1.07 mmol, 1.0 eq) was dissolved in THF (4 mL) and the reaction vessel was flushed with argon. Afterwards, PtO2 Het 174-1 (CAS # 1314-15-4, 21mg, 0.092 mmol, 0.087 eq) was added. The reaction was then evacuated and flushed with hydrogen and the pressure was adjusted to 10 bar. The mixture was heated at 50°C and stirring was continued at 10 bar H2for 18 hours. After cooling to room temperature, the vessel was flushed with argon and the mixture was filtered (Pall Acrodisc CR 25mm Syringe Filter 0.45 µm, PN 4219T). The solvent was removed under reduced pressure and the crude was purified by flash chromatography on silica gel (0% to 10% MeOH in DCM) to afford the title compound (278 mg, 74% yield) as colorless oil. LCMS m / z: 202.1[M+H]+, ESI pos. Step C: Lithium;1-(2-hydroxyethyl)-6-oxo-piperidine-3-carboxylate Aforementioned methyl 1-(2-hydroxyethyl)-6-oxo-piperidine-3-carboxylate (45 mg, 223.6 µmol, 1.0 eq) was dissolved in methanol (0.5 mL) and tetrahydrofuran (1.0 mL) and 1 M aqueous lithium hydroxide solution (0.34 mL, 0.34 mmol, 1.50 eq) was added to the reaction mixture, and it was stirred at room temperature for one hour. The reaction mixture was evaporated to dryness to afford the title compound (45 mg, 94% yield) as a white solid, which was used in the next step without further purification. Step D: 5-(5-Bromooxazolo[4,5-b]pyridin-2-yl)-1-(2-hydroxyethyl)piperidin-2-one To a mixture of 2-amino-6-bromo-pyridin-3-ol (CAS # 934758-27-7, 35 mg, 0.19 mmol, 1.0 eq) and aforementioned lithium;1-(2-hydroxyethyl)-6-oxo-piperidine-3-carboxylate (43.86 mg, 0.21 mmol, 1.1 eq) was added Eaton's Reagent (0.5 mL) at room temperature. The reaction mixture was stirred at 100°C overnight. Afterwards, the reaction mixture was cooled to room temperature, added dropwise onto ~50 mL saturated aq. NaHCO3-solution (strong gas evolution!) and extracted four times with a mixture of dichloromethane / methanol (9:1). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (gradient 0% to 15% methanol in dichloromethane) to afford the title compound (22 mg, 35% yield) as a white solid. Step E: 1-(2-Hydroxyethyl)-5-[5-[2-hydroxy-6-methyl-4-(trifluoromethyl)phenyl]-oxazolo[4,5- b]pyridin-2-yl]piperidin-2-one A mixture of 5-(5-bromooxazolo[4,5-b]pyridin-2-yl)-1-(2-hydroxyethyl)piperidin-2-one (15 mg, 0.044 mmol, 1.0 eq), 3-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5- (trifluoromethyl)phenol (CAS # 2557358-38-8, 20.57 mg, 0.068 mmol, 1.5 eq), cesium carbonate (43.3 mg, 0.13 mmol, 3.0 eq) and XPhos Pd G3(3.92 mg, 0.0046 mmol, 0.11 eq) were dissolved in 1,4-dioxane (75 µL) and water (20 µL) and 10-mL round bottom flask was flushed with argon and stirred at 90°C for 2h. Then, the reaction mixture was cooled to room temperature and extracted with a mixture of dichloromethane / methanol (19:1) and half-saturated aq. NH4Cl- solution. The organic layer was washed with water and brine. The aqueous layers were back- extracted twice with a mixture of dichloromethane / methanol (19:1). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by preparative HPLC (column: Gemini NX, 12 nm, 5 µm, 100 x 30 mm, solvents: MeCN / water + 0.1% TEA; gradient 5-50-100 MeCN in water; runtime 15 mins) to afford the title compound (10 mg, 47% yield) as a white solid. LCMS m / z: 436.1[M+H]+, ESI pos. Example 6, 6a and 6b: 5-[5-(2-Hydroxy-4,6-dimethyl-phenyl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one, (5S)-5-[5-(2-hydroxy-4,6-dimethyl-phenyl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5R)-5-[5-(2-hydroxy-4,6-dimethyl-phenyl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one and (5R)-5-[5-(2-hydroxy-4,6-dimethyl-phenyl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5S)-5-[5-(2-hydroxy-4,6-dimethyl-phenyl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one Step A: 5-[5-(2-Hydroxy-4,6-dimethyl-phenyl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one A mixture of Intermediate 3 (60 mg, 0.203 mmol, 1.0 eq), (2-hydroxy-4,6-dimethyl- phenyl)boronic acid (CAS # 1421935-36-5, 66 mg, 0.397 mmol, 2.0 eq), cesium carbonate (207 mg, 0.634 mmol, 3.0 eq) and XPhos Pd G3 (CAS # 1445085-55-1, 27 mg, 0.032 mmol, 0.156 eq) in 1,4-dioxane (1.4 mL) and water (0.335 mL) was flushed with argon and stirred at 95°C for 30 minutes. The reaction mixture was cooled to room temperature and then extracted with ethyl acetate and half-saturated aq. NH4Cl-solution. The aqueous layer was backextracted with ethyl acetate. The organic layers were washed with water and brine. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The crude was purified by flash chromatography (silica gel, 12g, gradient 0% to 10% methanol in dichloromethane). All fractions containing product were combined and concentrated in vacuo. The residue was triturated with ethyl acetate / heptane to afford the title compound Example 6 (43 mg, 62% yield) as yellow solid. LCMS: m / z 338.1[M+H]+, ESI pos. Step B: -5-[5-(2-Hydroxy-4,6-dimethyl-phenyl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or -5-[5-(2-hydroxy-4,6-dimethyl-phenyl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one and (5R)-5-[5-(2-hydroxy-4,6-dimethyl-phenyl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5S)-5- [5-(2-hydroxy-4,6-dimethyl-phenyl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one Chiral separation by SFC (column chiral OJ, 5um, 250 x 20 mm, eluent 35% heptane / EtOAc, 0.2% DEA) of aforementioned 5-[5-(2-hydroxy-4,6-dimethyl-phenyl)oxazolo[4,5-b]pyridin-2- yl]piperidin-2-one (43 mg, 0.127 mmol, 1.0 eq) yielded the two enantiomers: Example 6A (first eluting, Rt = 4.082 min) (15 mg, 34% yield) as light brown solid: LCMS: m / z 338.1[M+H]+, ESI pos. and Example 6B (second eluting, Rt = 4.648 min) (17 mg, 39% yield) as light brown solid: LCMS: m / z 338.1[M+H]+, ESI pos. Example 7: 5-[5-[4-Hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5-yl]oxazolo[4,5-b]pyridin-2- yl]hexahydropyrimidin-2-one Step A: 5-(5-Bromooxazolo[4,5-b]pyridin-2-yl)hexahydropyrimidin-2-one To a mixture of 2-amino-6-bromo-pyridin-3-ol (CAS # 934758-27-7, 250 mg, 1.32 mmol, 1.00 eq) and 2-oxohexahydropyrimidine-5-carboxylic acid (CAS # 1935892-31-1, 211 mg, 1.46 mmol, 1.11 eq) was added Eaton's Reagent (CAS # 39394-84-8, 1.0 mL, 1.32 mmol, 1.00 eq) at room temperature. The reaction mixture was stirred at 100 °C 16 h. The reaction mixture was cooled to room temperature, added dropwise onto ~25mL ice-cooled saturated aq. NaHCO3-solution (strong gas evolution) and extracted five times with a mixture of dichloromethane / methanol (9:1). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was adsorbed on ISOLUTE HM-N and purified by flash chromatography (silica gel, 12 g, gradient 0% to 10% methanol in dichloromethane) to afford the title compound (68 mg, 16% yield) as a brown solid. LCMS: m / z 297.0; 299.0 (Br isotopes) [M+H]+, ESI pos. Step B: 5-[5-[4-Hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5-yl]oxazolo[4,5-b]pyridin- 2-yl]hexahydropyrimidin-2-one A mixture of 5-(5-bromooxazolo[4,5-b]pyridin-2-yl)hexahydropyrimidin-2-one (64 mg, 0.20 mmol, 1.00 eq), 6-(methoxymethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3- dihydrobenzofuran-4-ol Intermediate 4 (106 mg, 0.33 mmol, 1.61 eq), potassium carbonate (110 mg, 0.80 mmol, 3.89 eq) and 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (CAS # 95464-05-4, 25 mg, 0.03 mmol, 0.15 eq) in 1,4-dioxane (1.4 mL) and water (0.70 mL) was flushed with argon and stirred at 90 °C for 2 h. The reaction mixture was cooled to room temperature and extracted with a mixture of dichloromethane / methanol (9:1) and half-saturated aq. NH4Cl-solution. The organic layer was washed with water and brine. The aqueous layers were backextracted twice with a mixture of dichloromethane / methanol (9:1). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was adsorbed on ISOLUTE HM-N and purified by flash chromatography (silica gel, 12 g, gradient 0% to 10% methanol in dichloromethane). The isolated product was triturated with ethyl acetate to afford the title compound (33 mg, 39% yield) as a brown solid. LCMS: m / z 397.2 [M+H]+, ESI pos. Example 8: 5-[5-(4-Hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2- yl]hexahydropyrimidin-2-one Step A: Ethyl 2-oxohexahydropyrimidine-5-carboxylate To a mixture of Pd / C (100.0 mg, 0.59 mmol, 0.1 eq, 10% purity on carbon) in methanol (5 mL) was added ethyl 2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxylate (CAS # 33458-27-4, 1.0 g, 5.88 mmol, 1.0 eq) under N2and the suspension was degassed in vacuum and purged with H2for several times. The mixture was stirred at 50 °C for 16 h under H2 (45 psi). Upon reaction completion, the mixture was cooled to 20 °C, filtered through a pad of celite and the filter cake was washed with methanol (50 mL×4). The combined filtrates were concentrated in vacuum to afford the title compound (900.0 mg, 89% yield) as a white solid.1H NMR (400 MHz, CD3OD): δ 4.18 (q, 2H), 3.49 - 3.45 (m, 4H), 2.99 - 2.90 (m, 1H), 1.27 (t, 3H). Step B: 2-Oxohexahydropyrimidine-5-carboxylic acid To a solution of aforementioned ethyl 2-oxohexahydropyrimidine-5-carboxylate (1.0 g, 5.81 mmol, 1.0 eq.) in THF (10 mL) and water (3 mL) was added LiOH•H2O (1.2 g, 29.04 mmol, 5.0 eq). Then the mixture was stirred at 20°C for 20 h. Upon reaction completion, THF was removed in vacuo and the aqueous phase was adjusted to pH = 4 with 1N HCl aqueous solution, leading to precipitation of a white solid. The mixture was filtered, and the filter cake was dried to afford the title compound (700.0 mg, 84% yield) as a white solid.1H NMR (400 MHz, DMSO-d6): δ 12.62 (br s, 1H), 6.17 (s, 2H), 3.29 - 3.15 (m, 4H), 2.77 (m, 1H). Step C: 5-(5-Bromooxazolo[4,5-b]pyridin-2-yl)hexahydropyrimidin-2-one A solution of aforementioned 2-oxohexahydropyrimidine-5-carboxylic acid (300.0 mg, 2.08 mmol, 1.0 eq.) and 2-amino-6-bromopyridin-3-ol (CAS # 934758-27-7, 472.1 mg, 2.5 mmol, 1.2 eq.) in Eaton's reagent (495.5 mg, 2.08 mmol, 1.0 eq.) was stirred at 100 °C for 12 h. Upon reaction completion, the above reaction mixture was cooled to 25°C and diluted with methanol (20 mL). The mixture was basified to pH = 7 using saturated aqueous NaHCO3 solution and stirred at 20°C for 20 minutes. The mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by reversed phase flash (column: Xtimate C18, 250mm*50mm*10μm; mobile phase: [water (0.1% ammonia hydroxide v / v)-MeCN]; B%: 30%-50%, 10 minutes) to afford the title compound (180.0 mg, 29% yield) as an off-white solid. LCMS: m / z 299.0 [M+2+H]+, ESI+pos. Step D: 5-[5-(4-Hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2- yl]hexahydropyrimidin-2-one To a solution of 5-(5-bromooxazolo[4,5-b]pyridin-2-yl)hexahydropyrimidin-2-one (60.0 mg, 0.2 mmol, 1.0 eq.) and Intermediate 2 (58.6 mg, 0.21 mmol, 1.05 eq.), KF (35.1 mg, 0.61 mmol, 3.0 eq.) in 1,4-dioxane (1 mL) and water (0.2 mL) was added Xphos Pd G3(34.2 mg, 0.04 mmol, 0.2 eq.). The reaction mixture was stirred at 80 °C for 2 h under N2. Upon reaction completion, the mixture was cooled to room temperature, filtered, and the filtrate was concentrated in vacuum. The residue was purified by prep-HPLC (column: Xtimate C18, 250mm*50mm*10μm; mobile phase: [water (0.1% ammonia hydroxide v / v)\MeCN]; B%: 5%-35%, 10 minutes) to afford the title compound (21.8 mg, 29% yield) as a light brown solid.LCMS: m / z 367.2 [M+H]+, ESI+pos. Example 9, 9a and 9b: 1-(2-Hydroxyethyl)-5-[5-[4-hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5- yl]oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one, (5R)-1-(2-hydroxyethyl)-5-[5-[4-hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5- yl]oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5S)-1-(2-hydroxyethyl)-5-[5-[4-hydroxy-6- (methoxymethyl)-2,3-dihydrobenzofuran-5-yl]oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one and (5S)-1-(2-hydroxyethyl)-5-[5-[4-hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5- yl]oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5R)-1-(2-hydroxyethyl)-5-[5-[4-hydroxy- 6-(methoxymethyl)-2,3-dihydrobenzofuran-5-yl]oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one Step A: 1-(2-Hydroxyethyl)-5-[5-[4-hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5- yl]oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one A mixture of 5-(5-bromooxazolo[4,5-b]pyridin-2-yl)-1-(2-hydroxyethyl)piperidin-2-one (Example 5, step D) (80 mg, 0.235 mmol, 1.0 eq), Intermediate 4 (115 mg, 0.376 mmol, 1.6 eq), potassium carbonate (CAS# 584-08-7, 143 mg, 1.03 mmol, 4.4 eq) and 1,1'- bis(diphenylphosphino)ferrocene-palladium(ii) dichloride dichloromethane complex (CAS # 95464-05-4, 29 mg, 0.035 mmol, 0.15 eq) in 1,4-dioxane (1.7 mL) and water (0.83 mL) was flushed with argon and stirred at 90v°C for 2 h. The reaction mixture was cooled to room temperature and extracted with EtOAc and half-saturated aq. NH4Cl-solution. The organic layer was washed with water and brine. The aqueous layers were backextracted twice with EtOAc. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography (silica Gel, 12g, gradient 0% to 10% methanol in EtOAc) to afford the title compound Example 9 (41 mg, 39%) as light yellow solid. LCMS: m / z 440.3[M+H]+, ESI pos. Step B: (5R)-1-(2-Hydroxyethyl)-5-[5-[4-hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5- yl]oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5S)-1-(2-hydroxyethyl)-5-[5-[4-hydroxy-6- (methoxymethyl)-2,3-dihydrobenzofuran-5-yl]oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one and (5S)-1-(2-hydroxyethyl)-5-[5-[4-hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5- yl]oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5R)-1-(2-hydroxyethyl)-5-[5-[4-hydroxy-6- (methoxymethyl)-2,3-dihydrobenzofuran-5-yl]oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one Chiral separation by SFC (column chiral, IA, 12nm, 5um, 250 x 4.6mm, eluent B: 45% methanol) of aforementioned 1-(2-hydroxyethyl)-5-[5-[4-hydroxy-6-(methoxymethyl)coumaran-5- yl]oxazolo[4,5-b]pyridin-2-yl]-2-piperidone (41 mg, 0.09 mmol, 1.0 eq) afforded the two enantiomers. Example 9a (first eluting, Rt = 2.015 min) (6 mg, 14% yield) as an yellow solid: LCMS: m / z 440.3[M+H]+, ESI pos and Example 9b (second eluting, Rt = 2.74 min) (9 mg, 21% yield) as an yellow solid: LCMS: m / z 440.3[M+H]+, ESI pos. Example 10, 10a and 10b: 1-(2-Hydroxyethyl)-5-[5-(4-hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5- b]pyridin-2-yl]piperidin-2-one, (5S)-1-(2-hydroxyethyl)-5-[5-(4-hydroxy-6-methyl-2,3- dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5R)-1-(2- hydroxyethyl)-5-[5-(4-hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5- b]pyridin-2-yl]piperidin-2-one and (5R)-1-(2-hydroxyethyl)-5-[5-(4-hydroxy-6-methyl-2,3- dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5S)-1-(2- hydroxyethyl)-5-[5-(4-hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5- b]pyridin-2-yl]piperidin-2-one Step A: 1-(2-Hydroxyethyl)-5-[5-(4-hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5- b]pyridin-2-yl]piperidin-2-one A mixture of 5-(5-bromooxazolo[4,5-b]pyridin-2-yl)-1-(2-hydroxyethyl)piperidin-2-one (Example 5, step D) (120 mg, 0.353 mmol, 1.0 eq), Intermediate 2 (173 mg, 0.564 mmol, 1.6 eq), potassium carbonate (215 mg, 1.55 mmol, 4.4 eq) and1,1'-bis(diphenylphosphino)ferrocene- palladium(ii) dichloride dichloromethane complex (CAS # 72287-26-4, 43 mg, 0.053 mmol, 0.15 eq) in 1,4-dioxane (2.5 mL) and water (1.25 mL) was flushed with argon and stirred at 90 °C for 3 h. The reaction mixture was cooled to room temperature and extracted with EtOAc and half- saturated aq. NH4Cl-solution. The organic layer was washed with water and brine. The aqueous layers were backextracted twice with EtOAc. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The crude was purified by flash chromatography (Si- amine, 12g, gradient 0% to 10% methanol in DCM) to afford the title compound Example 10 (80 mg, 48% yield) as light yellow solid. LCMS: m / z 410.3[M+H]+, ESI pos. Step B: (5S)-1-(2-Hydroxyethyl)-5-[5-(4-hydroxy-6-methyl-2,3-dihydrobenzofuran-5- yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5R)-1-(2-hydroxyethyl)-5-[5-(4-hydroxy-6- methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one and (5R)-1-(2- hydroxyethyl)-5-[5-(4-hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2- yl]piperidin-2-one or (5S)-1-(2-hydroxyethyl)-5-[5-(4-hydroxy-6-methyl-2,3-dihydrobenzofuran- 5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one Chiral separation by SFC (column chiral, Whelk (r,r), 5um, 250 x 20 mm, eluent B: 50% methanol, 0.2% DEA) of aforementioned 1-(2-hydroxyethyl)-5-[5-(4-hydroxy-6-methyl-2,3- dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one (102 mg, 0.25 mmol, 1.0 eq) afforded the two enantiomers: Example 10A (first eluting, Rt = 2.73 min) (39 mg, 36% yield) as an yellow solid: LCMS: m / z 410.3[M+H]+, ESI pos and Example 10B (second eluting, Rt = 3.0 min) (36 mg, 34% yield) as an yellow solid: LCMS: m / z 410.3[M+H]+, ESI pos. Example 11: 4-(Hydroxymethyl)-5-[5-[2-hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5- b]pyridin-2-yl]piperidin-2-one Step A: Diethyl 3-(benzyloxymethyl)-2-cyano-pentanedioate To a solution of ethyl (E)-4-benzyloxybut-2-enoate (CAS# 70150-60-6, 3.5 g, 15.89 mmol, 1.0 eq.) and ethyl cyanoacetate (2.7 g, 23.84 mmol, 1.5 eq.) in THF (80 mL) was added DBU (1.2 g, 4.77 mmol, 0.3 eq). The mixture was stirred at 50°C for 6 hours. The above reaction mixture was quenched with saturated NH4Cl aqueous solution (30 mL), extracted with ethyl acetate (20 mL x 3). The combined organic phases were washed with brine (30 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (petroleum ether: ethyl acetate = 1:0 to 0:1) to afford the title compound (2.35 g, 44% yield) as yellow oil.1H NMR (400 MHz, DMSO-d6): δ 7.64 - 6.90 (m, 5H), 4.56 - 4.47 (m, 1H), 4.47 - 4.40 (m, 1H), 4.37 (t, 1H), 4.18 - 3.98 (m, 4H), 3.56 - 3.51 (m, 1H), 3.47 - 3.38 (m, 1H), 3.01 - 2.79 (m, 1H), 2.47 - 2.41 (m, 2H), 1.26 - 1.07 (m, 6H). Step B: Ethyl 4-(benzyloxymethyl)-6-oxo-piperidine-3-carboxylate To a solution of diethyl 3-(benzyloxymethyl)-2-cyano-pentanedioate (2.35 g, 11.7 mmol, 1.0 eq.) and CoCl2.6H2O (4.15 g, 29.25 mmol, 2.5 eq.) in methanol (30 mL) was added NaBH4(1.78 g, 78.77 mmol, 6.73 eq.) at 0°C under nitrogen. The mixture was stirred at 70 °C for 1 h, then cooled to rt and quenched with 1 M HCl aqueous solution (200 mL). The mixture was extracted with ethyl acetate (200 mL x 3). The combined organic phases were washed with brine (200 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column (petroleum ether: ethyl acetate = 1:0 to 0:1) to afford the title compound (1.15 g, 49% yield) as yellow oil. LCMS: m / z 292.1 [M+H]+, ESI+pos. Step C: 4-(Benzyloxymethyl)-6-oxo-piperidine-3-carboxylic acid To a solution of ethyl 4-(benzyloxymethyl)-6-oxo-piperidine-3-carboxylate (1.15 g, 4.81 mmol, 1.0 eq.) in methanol (50 mL) and water (10 mL) was added LiOH•H2O (0.35 g, 9.61 mmol, 2.0 eq.). The mixture was stirred at 45 °C for 4 h. The above reaction mixture was cooled to 0 °C and adjusted to pH = 5 with 1 M HCl aqueous solution. The above mixture was purified by prep-HPLC (column: Xtimate C18, 250mm*50mm*10μm; mobile phase: 0.1% TFA, water-MeCN), to afford the title compound (600.0 mg, 42% yield) as a white solid. LCMS: m / z 264.1 [M+H]+, ESI+pos. Step D: Isobutoxycarbonyl 4-(benzyloxymethyl)-6-oxo-piperidine-3-carboxylate To a solution of 4-(benzyloxymethyl)-6-oxo-piperidine-3-carboxylic acid (600.0 mg, 1.98 mmol, 1.0 eq.), TEA (0.60 mL, 3.95 mmol, 2.0 eq.) in DMF (10 mL) was added isobutyl chloroformate (593.4 mg, 4.35 mmol, 2.0 eq.). Then the mixture was stirred at 25 °C for 1 h. The mixture was concentrated under reduced pressure to afford the title compound (690.0 mg, 37% yield) as yellow oil, which was used directly in the next step. Step E: 4-((Benzyloxy)methyl)-N-(6-bromo-3-hydroxypyridin-2-yl)-6-oxopiperidine-3- carboxamide To a solution of aforementioned isobutoxycarbonyl 4-(benzyloxymethyl)-6-oxo-piperidine-3- carboxylate (690 mg, 1.9 mmol, 1.0 eq.), TEA (0.6 mL, 3.95 mmol, 2.0 eq.) in DMF (10 mL) was added 2-amino-6-bromopyridin-3-ol (CAS # 934758-7-7, 538.3 mg, 2.85 mmol, 1.5 eq). The mixture was stirred at 25 °C for 1 h. The above reaction mixture was diluted with water (50 mL), and extracted with ethyl acetate (100 mL x 3). The combined organic phases were washed with brine (200 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (petroleum ether: ethyl acetate = 20:1 to 0:1) to afford the title compound (520.0 mg, 76% yield) as a yellow solid. LCMS: m / z 436.0[M+H]+, ESI+pos. Step F: 4-((Benzyloxy)methyl)-5-(5-bromooxazolo[4,5-b]pyridin-2-yl)piperidin-2-one A solution of 4-((benzyloxy)methyl)-N-(6-bromo-3-hydroxypyridin-2-yl)-6-oxopiperidine-3- carboxamide (520.0 mg, 1.20 mmol, 1.0 eq.) in PPSE (4.0 mL) was stirred at 100 °C for 2 h. The reaction mixture was cooled to room temperature, poured into MeCN (250 mL) and adjusted to pH = 8 with 50 g of Amberlyst (R) A21, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (petroleum ether: ethyl acetate = 50:1 to 0:1) to afford the title compound (80.0 mg, 11% yield) as a white solid. LCMS: m / z 418.0[M+H]+, ESI+pos. Step G: 4-(Benzyloxymethyl)-5-[5-[2-hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5- b]pyridin-2-yl]piperidin-2-one To a solution of 4-((benzyloxy)methyl)-5-(5-bromooxazolo[4,5-b]pyridin-2-yl)piperidin-2-one (80.0 mg, 0.19 mmol, 1.0 eq.), KF (27.8 mg, 0.48 mmol, 2.5 eq.), 3-methyl-2-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)phenol (104.5 mg, 0.35 mmol, 1.8 eq, CAS# 2557358-38-8) in 1,4-dioxane (10 mL) and water (0.2 mL) was added XPhos Pd G3(16.2 mg, 0.02 mmol, 0.1 eq.) under N2atmosphere, then the mixture was stirred at 80°C for 2 hours. The above reaction mixture was cooled to room temperature, diluted with water (50 mL), and extracted with ethyl acetate (50 mL x 3). The combined organic phases were washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate: methanol = 1:0 to 0:1) to afford the title compound (60.0 mg, 56% yield) as a yellow solid. LCMS: m / z 512.1[M+H]+, ESI+pos. Step H: 4-(Hydroxymethyl)-5-[5-[2-hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5- b]pyridin-2-yl]piperidin-2-one To a solution of 4-(benzyloxymethyl)-5-[5-[2-hydroxy-6-methyl-4-(trifluoromethyl)- phenyl]oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one (50.0 mg, 0.1 mmol, 1.0 eq.) in methanol (20 mL) was added Pd / C (11.7 mg, 0.01 mmol, 0.1 eq., 10% purity on carbon) under N2, then the mixture was stirred 30°C for 6 hours under H2atmosphere (1100 mmHg). The above reaction mixture was cooled to room temperature, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by prep-HPLC (column: Xtimate C18, 250mm*50mm*10μm; mobile phase: [water (0.1% ammonia hydroxide v / v)-MeCN]; B%: 5%-35%, 10 minutes) to afford the title compound Example 11 (12.69 mg, 26% yield) as a white solid. LCMS: m / z 422.0 [M+H]+, ESI+pos. Example 12: 3-Hydroxy-5-[5-[2-hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin-2- yl]piperidin-2-one Step A: 4-Benzyloxy-5-methoxy-2-methylene-5-oxo-pentanoic acid To a solution of methyl 2-benzyloxyacetate (CAS # 31600-43-8, 3.28 g, 18.18 mmol, 1.2 eq) in THF (48 mL) was slowly dropped lithium hexamethyldisilazane (38.0 mL, 38.0 mmol, 2.51 eq., 1M in hexane solution) at -70°C under nitrogen, the mixture was stirred at -70°C for 0.5 hour. Then a solution of 2-(bromomethyl)acrylic acid (CAS # 72707-66-5, 2.5 g, 15.15 mmol, 1.0 eq.) in THF (5 mL) was slowly dropped to the above mixture at -70 °C, then the resulting mixture was stirred at -70°C for 1 hour. Upon reaction completion, the above reaction mixture was quenched with saturated NH4Cl aqueous solution (200 mL) at 0°C, then adjusted to pH = 2 with 1 M HCl solution. The mixture was extracted with ethyl acetate (100 mL x 3). The combined organic phases were washed with brine (200 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure to afford the title compound (4.0 g, quantitative) as yellow oil. Step B: 5-Benzyloxy-1-[(4-methoxyphenyl)methyl]-6-oxo-piperidine-3-carboxylic acid To a solution of 4-aminomethyl-anisole (19.8 mL, 151.4 mmol, 5.0 eq.) in methanol (76 mL) was added the solution of aforementioned 4-benzyloxy-5-methoxy-2-methylene-5-oxo-pentanoic acid (8.0 g, 30.3 mmol, 1.0 eq.) in methanol (20 mL) at 70°C, then stirred at 70 °C for 24 h. Upon reaction completion, the above reaction mixture was cooled to room temperature, diluted with water (300 mL), adjusted to pH = 12 with 1M NaOH aqueous solution, washed with ethyl acetate (200 mL x 2). Then the aqueous phase was adjusted to pH = 2 with diluted HCl (1 M in water), then extracted with ethyl acetate (200 mL x 2). The combined organic phases were washed with brine (300 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by prep-HPLC (column: Xtimate C18, 250mm*50mm*10μm; mobile phase: [water (0.1% FA v / v)-MeCN]; B%: 5%-35%, 10 minutes) to afford the title compound (1.6 g, 64% yield) as yellow oil. LCMS: m / z 370.2[M+H]+, ESI+pos. Step C: 5-Benzyloxy-1-[(4-methoxyphenyl)methyl]-6-oxo-piperidine-3-carbonyl chloride To a solution of 5-benzyloxy-1-[(4-methoxyphenyl)methyl]-6-oxo-piperidine-3-carboxylic acid (1.6 g, 4.33 mmol, 1.0 eq.) in DCM (16 mL) was added oxalyl chloride (0.73 mL, 8.66 mmol, 1.0 eq.), and the mixture was stirred at 25 °C for 1 h. Upon the reaction completion, the mixture was concentrated under reduced pressure to afford the title compound (1.6 g, 95% yield) as yellow oil and without purification, used for next step. Step D: 5-Benzyloxy-N-(6-bromo-3-hydroxy-2-pyridyl)-1-[(4-methoxyphenyl)methyl]-6-oxo- piperidine-3-carboxamide To a solution of 2-amino-6-bromopyridin-3-ol (1.16 g, 6.16 mmol, 1.49 eq, CAS # 934758-27-7) and TEA (0.84 g, 8.28 mmol, 2.01 eq.) in THF (10 mL) was added a solution of 5-benzyloxy-1- [(4-methoxyphenyl)methyl]-6-oxo-piperidine-3-carbonyl chloride (1.6 g, 4.13 mmol, 1.0 eq.) in DCM (10 mL) dropwise at 0 °C, then the mixture was stirred at 25 °C for 1.5 h. Upon the reaction completion, the above reaction solution was diluted with water (200 mL), extracted with ethyl acetate (100 mL x 3). The combined organic phases were washed with brine (200 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (SiO2, petroleum ether: ethyl acetate = 1:0 to 0:1) to afford the title compound (1.2 g, 45% yield) as a yellow solid. LCMS: m / z 540.1, [M+H]+, ESI+pos. Step E: 3-Benzyloxy-5-(5-bromooxazolo[4,5-b]pyridin-2-yl)-1-[(4-methoxyphenyl)methyl]- piperidin-2-one A mixture of 5-benzyloxy-N-(6-bromo-3-hydroxy-2-pyridyl)-1-[(4-methoxyphenyl)methyl]-6- oxo-piperidine-3-carboxamide (800.0 mg, 1.48 mmol, 1.0 eq.) in PPSE (4.0 mL, 7.4 mmol, 5.0 eq.) was stirred at 100 °C for 2 h. Upon the reaction completion, the above reaction solution was cooled to room temperature, diluted with acetonitrile (100 mL), then adjusted to pH = 7 with saturated NaHCO3 aqueous, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash (CombiFlash [water (0.1% FA v / v)- acetonitrile];) to afford the title compound (300.0 mg, 41% yield) as a yellow solid. LCMS: m / z 524.1[M+2+H]+, ESI+pos. Step F: 5-(5-Bromooxazolo[4,5-b]pyridin-2-yl)-3-hydroxy-piperidin-2-one To a solution of 3-benzyloxy-5-(5-bromooxazolo[4,5-b]pyridin-2-yl)-1-[(4- methoxyphenyl)methyl]-piperidin-2-one (300.0 mg, 0.57 mmol, 1.0 eq.) in acetonitrile (6 mL) was added a solution of ammonium cerium (IV) nitrate (1.28 mL, 3.45 mmol, 6.0 eq.) in water (6 mL) at 0°C, then the mixture was stirred at 0°C for 1 hour. Upon reaction completion, the above reaction mixture was quenched with saturated aqueous NaHCO3solution, filtered, and the filtrate was purified by reversed phase flash (CombiFlash [water (0.1% FA v / v)- acetonitrile];) to afford the title compound (25.0 mg, 9% yield) as a brown solid. LCMS: m / z 314.0[M+2+H]+, ESI+pos. Step G: 3-Hydroxy-5-[5-[2-hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin- 2-yl]piperidin-2-one To a solution of 5-(5-bromooxazolo[4,5-b]pyridin-2-yl)-3-hydroxy-piperidin-2-one (20.0 mg, 0.06 mmol, 1.0 eq.) and 3-methyl -2-(4,4,5,5-tetramethyl -1,3,2-dioxaborolan -2-yl) -5- (trifluoromethyl)phenol (25.2 mg, 0.08 mmol, 1.3 eq, CAS# 2557358-38-8) in DMF (1 mL) was added K3PO4(40.8 mg, 0.19 mmol, 3.0 eq.) and XPhos Pd G3(10.8 mg, 0.01 mmol, 0.2 eq.). The mixture was then stirred at 60°C for 2 hours under nitrogen atmosphere. Upon reaction completion, the above mixture was cooled to room temperature and diluted with methanol (10 mL), filtered and the filtrate was concentrated under reduced pressure. The residue purified by prep-HPLC (Column Waters xbridge 150*25mm 10um, mobile phase: [water (0.1% ammonia hydroxide v / v)- acetonitrile]; B%: 29%-49%, 8 minutes) to afford the title compound Example 12 (14.49 mg, 55% yield) as a white solid. LCMS: m / z 408.2[M+H]+, ESI+pos. Example 13: 5-[5-(4-Hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyrazin-2- yl]hexahydropyrimidin-2-one;formic acid Step A: 6-Bromo-3-(2-trimethylsilylethoxy)pyrazin-2-amine To a mixture of 2-(trimethylsilyl)ethanol (6.9 mL, 47.98 mmol, 2.0 eq) in THF (30 mL) was added NaH (2.01 g, 50.37 mmol, 2.1 eq, 60% purity in mineral oil) under N2, then the mixture was stirred at 80°C for 1 hour. The mixture was cooled to room temperature. Then 6-bromo-3-chloro-pyrazin- 2-amine (5.0 g, 23.99 mmol, 1.0 eq.) was added to the above reaction mixture at 20°C, and the resulting mixture was heated at 80°C for 15 hours under N2. Upon reaction completion, the mixture was cooled to room temperature and quenched with saturated NH4Cl (100 mL) aqueous solution, and extracted with ethyl acetate (100 mL x 3). The combined organic phases were washed with brine (100 mL x 2), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (petroleum ether / ethyl acetate, 1:0 to 4:1) to afford the title compound (2.8 g, 40% yield) as a yellow solid.1H NMR (400 MHz, CD3OD): δ 7.30 (s, 1H), 4.36 - 4.31 (m, 2H), 1.18 - 1.13 (m, 2H), 0.03 (s, 9H). Step A`: 2-Oxohexahydropyrimidine-5-carbonyl chloride To a mixture of 2-oxohexahydropyrimidine-5-carboxylic acid (3.0 g, 20.81 mmol, 1.0 eq.) (Example 8, step B) and DMF (20 mg, 0.21 mmol, 0.01 eq.) in DCM (30 mL) was added oxalyl dichloride (2.6 mL, 31.22 mmol, 1.5 eq.). The mixture was stirred at 25°C for 2 hours under nitrogen. Upon reaction completion, the mixture was concentrated under reduced pressure. The residue was triturated with hexane (30 mL), filtered and the filter cake was collected to afford the title compound (3.0 g, 89% yield) as a white solid. Step B: N-[6-Bromo-3-(2-trimethylsilylethoxy)pyrazin-2-yl]-2-oxo-hexahydropyrimidine-5- carboxamide To a solution of 6-bromo-3-(2-trimethylsilylethoxy)pyrazin-2-amine (2.41 g, 8.3 mmol, 0.45 eq.) in THF (20 mL) was added NaH (2.21 g, 55.36 mmol, 3.0 eq., 60% purity in mineral oil) at 0°C under N2, the mixture was stirred at 20°C for 0.5 hour. Then a solution of aforementioned 2- oxohexahydropyrimidine-5-carbonyl chloride (3.0 g, 18.45 mmol, 1.0 eq.) in THF (20 mL) was dropwise added to the above reaction mixture at 0°C. The resulting mixture was stirred at 20°C for 0.5 hour under N2. Upon reaction completion, the mixture was quenched with saturated aqueous NH4Cl (100 mL) solution at 0°C and extracted with ethyl acetate (100 mL x 3). Combined extracts were washed with brine (60 mL x 2), dried over Na2SO4, filtered and the filtrate was concentrated in vacuum. The residue was purified by silica gel column chromatography (ethyl acetate: methanol = 1:0 to 5:1) to afford the title compound (370.0 mg, 4% yield) as a white solid.1H NMR (400 MHz, CD3OD): δ 7.97 (s, 1H), 4.45 - 4.39 (m, 2H), 3.48 - 3.36 (m, 5H), 1.14 - 1.09 (m, 2H), 0.00 (s, 9H). Step C: N-[6-(4-hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)-3-(2-trimethylsilylethoxy)- pyrazin-2-yl]-2-oxo-hexahydropyrimidine-5-carboxamide To a solution of N-[6-bromo-3-(2-trimethylsilylethoxy)pyrazin-2-yl]-2-oxo- hexahydropyrimidine-5-carboxamide (100.0 mg, 0.24 mmol, 1.0 eq.) and 6-methyl-5-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydrobenzofuran-4-ol Intermediate 2 (69.6 mg, 0.25 mmol, 1.05 eq.), CsF (109.4 mg, 0.72 mmol, 3.0 eq.) in 1,4-dioxane (2.0 mL) and water (0.4 mL) was added XPhos Pd G3 (40.7 mg, 0.05 mmol, 0.2 eq.). Then the mixture was stirred at 80°C for 2 hours under N2. Upon reaction completion, the mixture was cooled to room temperature and filtered, the filtrate was concentrated under reduced pressure. The residue was purified by reversed phase flash (column: Xtimate C18, 250mm*50mm*10μm; mobile phase: [water (0.1% TFA v / v)- MeCN]; B%: 30%-50%, 10 minutes) and lyophilized to afford the title compound (110.0 mg, 76% yield) as a yellow solid. LCMS: m / z 486.2 [M+H]+, ESI+pos. Step D: N-[3-hydroxy-6-(4-hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)pyrazin-2-yl]-2-oxo- hexahydropyrimidine-5-carboxamide A solution of N-[6-(4-hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)-3-(2- trimethylsilylethoxy)pyrazin-2-yl]-2-oxo-hexahydropyrimidine-5-carboxamide (100.0 mg, 0.21 mmol, 1.0 eq.) and TFA (0.5 mL) in DCM (2 mL) was stirred at 20°C for 1 hour. Upon reaction completion, the mixture was concentrated in vacuum. The residue was triturated with ethyl acetate (5 mL x 2) and filtered. The filter cake was collected to afford the title compound (40.0 mg, 39% yield) as a yellow solid. LCMS: m / z 386.1 [M+H]+, ESI+pos. Step E: 5-[5-(4-Hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyrazin-2- yl]hexahydropyrimidin-2-one;formic acid A mixture of N-[3-hydroxy-6-(4-hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)pyrazin-2-yl]-2- oxo-hexahydropyrimidine-5-carboxamide (20.0 mg, 0.05 mmol, 1.0 eq.) and PPSE (0.5 mL) was stirred at 130°C for 2 hours. Upon the reaction completion, the reaction mixture was cooled to room temperature and poured into ice-water (5 mL). The mixture was adjusted to pH= 8 by using saturated aqueous NaHCO3 solution, filtered, and the filtrate was concentrated in vacuum. The residue was purified by prep-HPLC (column: Xtimate C18, 250mm*50mm*10μm; mobile phase: [water (0.1% FA v / v)\MeCN]; B%: 5%-35%, 10 minutes) to afford the title compound Example 13 (1.2 mg, 5% yield) as a light yellow solid. LCMS: m / z 368.1 [M+H]+, ESI+pos. Example A A compound of formula I can be used in a manner known per se as the active ingredient for the production of tablets of the following composition: Per tablet Active ingredient 200 mg Microcrystalline cellulose 155 mg Corn starch 25 mg Talc 25 mg Hydroxypropylmethylcellulose 20 mg 425 mg Example B A compound of formula I can be used in a manner known per se as the active ingredient for the production of capsules of the following composition: Per capsule Active ingredient 100.0 mg Corn starch 20.0 mg Lactose 95.0 mg Talc 4.5 mg Magnesium stearate 0.5 mg 220.0 mg Claims

Claims

1. A compound of formula Iwherein R1is halo, haloalkyl, or alkyl, and R9is H, or R1and R9and the atoms to which they are attached form a 5-membered cycloalkyl or a 5- membered heterocycle comprising 1 O heteroatom; R2is methyl or methoxyalkyl; A1 is –CH- or –N-; Y1 is CH-Rcor NRnand Y2 is CH-Rcor NRn, wherein at least one of Y1 and Y2 must be NRn; Rcis H, OH, alkyl, hydroxyalkyl, or alkoxy; Rnis H, alkyl or hydroxyalkyl; Z is H, OH, alkoxy or hydroxyalkyl, wherein if R1is halo or haloalykl, then one of Z, Rcor Rnmust not be H; and pharmaceutically acceptable salts thereof.

2. A compound according to claim 1, wherein R1is haloalkyl and R9is H, or R1and R9and the atoms to which they are attached form a 5-membered cycloalkyl or a 5-membered heterocycle comprising 1 O heteroatom.

3. A compound according to any of claims 1 to 2, wherein R2is methyl.

4. A compound according to any of claims 1 to 3, wherein A1is –CH-.

5. A compound according to any of claims 1 to 4, wherein Rcis H, OH, hydroxyalkyl or alkoxy.

6. A compound according to any of claims 1 to 5, wherein Rcis H or alkoxy.

7. A compound according to any of claims 1 to 6, wherein Rnis H, or hydroxyalkyl.

8. A compound according to any of claims 1 to 7, wherein Rnis H.

9. A compound according to any of claims 1 to 8, wherein Z is H or OH, wherein if R1is haloalkyl, then one of Z, Rcor Rnmust not be H.

10. A compound according to any of claims 1 to 6, where one of Z or Rcis alkoxy.

11. A compound according to claim 1 wherein both Y1and Y2are N.

12. A compound according to claim 1, wherein, R1is haloalkyl, and R9is H, or R1and R9and the atoms to which they are attached form a 5-membered cycloalkyl or a 5- membered heterocycle comprising 1 O heteroatom; R2is methyl; A1is –CH-; Y1is CH-Rcor NRnand Y2is CH-Rcor NRn, wherein one of Y1and Y2is NRn; Rcis H or alkoxy; Rnis H or hydroxyalkyl; Z is H or OH, wherein if R1is haloalykl, then one of Z, Rcor Rnmust not be H; and pharmaceutically acceptable salts thereof.

13. A compound according to claim 1, wherein, R1is haloalkyl, and R9is H, or R1and R9and the atoms to which they are attached form a 5-membered cycloalkyl or a 5- membered heterocycle comprising 1 O heteroatom; R2is methyl; A1 is –CH-; Y1 is CH-Rcor NRnand Y2 is CH-Rcor NRn, wherein one of Y1 and Y2 is NRn; Rcis H or alkoxy; Rnis H; Z is H or OH, wherein if R1is haloalykl, then one of Z, Rcor Rnmust not be H; and pharmaceutically acceptable salts thereof.

14. A compound according to claim 1, wherein, R1and R9and the atoms to which they are attached form a 5-membered cycloalkyl or a 5- membered heterocycle comprising 1 O heteroatom; R2is methyl; A1is –CH-; Y1 is CH-Rcor NRnand Y2 is CH-Rcor NRn, wherein one of Y1 and Y2 is NRn; Rcis H; Rnis H; Z is H; and pharmaceutically acceptable salts thereof.

15. A compound according to claim 1, wherein R1and R9and the atoms to which they are attached form a 5-membered cycloalkyl or a 5 membered heterocycle comprising 1 O heteroatom; R2is CH2-methoxy or methyl; A1 is –CH-; Y1 and Y2 are both N; Rcis H; Rnis H; Z is H; and pharmaceutically acceptable salts thereof. 6 A compound according to any one of claims 1 to 11, selected from 5-[5-(4-Hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one; (5S)-5-[5-(4-Hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one; (5R)-5-[5-(4-Hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one; rel-(3R,5R)-5-[5-[2-Hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin- 2-yl]-3-methoxy-piperidin-2-one or rel-(3S,5R)-5-[5-[2-hydroxy-6-methyl-4- (trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin-2-yl]-3-methoxy-piperidin-2-one;rel-(3S,5R)-5-[5-[2-Hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin- 2-yl]-3-methoxy-piperidin-2-one or rel-(3R,5R)-5-[5-[2-hydroxy-6-methyl-4- (trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin-2-yl]-3-methoxy-piperidin-2-one; (5S)-5-[5-(4-Hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2- yl]piperidin-2-one; (5R)-5-[5-(4-Hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2- yl]piperidin-2-one; 5-Hydroxy-5-[5-[2-hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin- 2-yl]piperidin-2-one; and pharmaceutically acceptable salts thereof. A compound according to any one of claims 1 to 11, selected from 5-[5-(2-hydroxy-4,6-dimethyl-phenyl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one; (5S)-5-[5-(2-hydroxy-4,6-dimethyl-phenyl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5R)-5-[5-(2-hydroxy-4,6-dimethyl-phenyl)oxazolo[4,5-b]pyridin-2-yl]piperidin- 2-one; (5R)-5-[5-(2-hydroxy-4,6-dimethyl-phenyl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5S)-5-[5-(2-hydroxy-4,6-dimethyl-phenyl)oxazolo[4,5-b]pyridin-2-yl]piperidin- 2-one; 5-[5-[4-Hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5-yl]oxazolo[4,5-b]pyridin- 2-yl]hexahydropyrimidin-2-one; 5-[5-(4-hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2- yl]hexahydropyrimidin-2-one; 1-(2-hydroxyethyl)-5-[5-[4-hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5- yl]oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one;(5R)-1-(2-hydroxyethyl)-5-[5-[4-hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5- yl]oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5S)-1-(2-hydroxyethyl)-5-[5-[4- hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5-yl]oxazolo[4,5-b]pyridin- 2-yl]piperidin-2-one; (5S)-1-(2-hydroxyethyl)-5-[5-[4-hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5- yl]oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5R)-1-(2-hydroxyethyl)-5-[5- [4-hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5-yl]oxazolo[4,5- b]pyridin-2-yl]piperidin-2-one; 1-(2-hydroxyethyl)-5-[5-(4-hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5- b]pyridin-2-yl]piperidin-2-one; (5R)-1-(2-hydroxyethyl)-5-[5-[4-hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5- yl]oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5S)-1-(2-hydroxyethyl)-5-[5-[4- hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5-yl]oxazolo[4,5-b]pyridin- 2-yl]piperidin-2-one; (5S)-1-(2-hydroxyethyl)-5-[5-[4-hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5- yl]oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or (5R)-1-(2-hydroxyethyl)-5-[5- [4-hydroxy-6-(methoxymethyl)-2,3-dihydrobenzofuran-5-yl]oxazolo[4,5- b]pyridin-2-yl]piperidin-2-one; 4-(hydroxymethyl)-5-[5-[2-hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5- b]pyridin-2-yl]piperidin-2-one; 3-hydroxy-5-[5-[2-hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin-2- yl]piperidin-2-one; 5-[5-(4-Hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyrazin-2- yl]hexahydropyrimidin-2-one;formic acid; and pharmaceutically acceptable salts thereof. A compound according to claim 1, wherein the compound is 1-(2-Hydroxyethyl)-5-[5-[2- hydroxy-6-methyl-4-(trifluoromethyl)phenyl]-oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one or a pharmaceutically acceptable salt thereof.

19. A compound according to any one of claims 1 to 18, selected from 5-[5-(4-Hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one; (5S)-5-[5-(4-Hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one; (5R)-5-[5-(4-Hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one; rel-(3R,5R)-5-[5-[2-Hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin- 2-yl]-3-methoxy-piperidin-2-one or rel-(3S,5R)-5-[5-[2-hydroxy-6-methyl-4- (trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin-2-yl]-3-methoxy-piperidin-2-one; rel-(3S,5R)-5-[5-[2-Hydroxy-6-methyl-4-(trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin- 2-yl]-3-methoxy-piperidin-2-one or rel-(3R,5R)-5-[5-[2-hydroxy-6-methyl-4- (trifluoromethyl)phenyl]oxazolo[4,5-b]pyridin-2-yl]-3-methoxy-piperidin-2-one; (5S)-5-[5-(4-Hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2- yl]piperidin-2-one; (5R)-5-[5-(4-Hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2- yl]piperidin-2-one; and pharmaceutically acceptable salts thereof. 0 A compound according to any one of claims 1 to 19, selected from 5-[5-(4-hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one; (5S)-5-[5-(4-hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one; (5R)-5-[5-(4-hydroxy-6-methyl-indan-5-yl)oxazolo[4,5-b]pyridin-2-yl]piperidin-2-one; (5S)-5-[5-(4-hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2- yl]piperidin-2-one; (5R)-5-[5-(4-hydroxy-6-methyl-2,3-dihydrobenzofuran-5-yl)oxazolo[4,5-b]pyridin-2- yl]piperidin-2-one; and pharmaceutically acceptable salts thereof.

21. A compound according to any one of claims 1 to 20 for use in the treatment or prevention of a disease, disorder or condition, wherein the disease, disorder or condition is responsive to NLRP3 inhibition.

22. A pharmaceutical composition comprising a compound according to any one of claims 1 to 20 and a therapeutically inert carrier.

23. The use of a compound according to any one of claims 1 to 20 for the treatment or prophylaxis of a disease, disorder or condition, wherein the disease, disorder or condition is responsive to NLRP3 inhibition.

24. A compound according to any one of claims 1 to 20 for the treatment or prophylaxis of a disease, disorder or condition selected from Asthma or COPD.

25. A compound according to any one of claims 1 to 20 for the treatment or prophylaxis of a disease, disorder or condition selected from Parkinson’s Disease or Alzheimer’s Disease.

26. The use of a compound according to any one of claims 1 to 20 for the preparation of a medicament for the treatment or prophylaxis of a disease, disorder or condition selected from Asthma or COPD.

27. The use of a compound according to any one of claims 1 to 20 for the preparation of a medicament for the treatment or prophylaxis of a disease, disorder or condition selected from Parkinson’s Disease or Alzheimer’s Disease.

28. A method of inhibiting NLRP3, which method comprises administering an effective amount of a compound as claimed in any one of claims 1 to 20 to inhibit NLRP3.

29. A method for the treatment or prophylaxis of a disease, disorder or condition, which method comprises administering an effective amount of a compound according to any one of claims 1 to 20, wherein the disease, disorder or condition is selected from Asthma or COPD.

30. A method for the treatment or prophylaxis of a disease, disorder or condition, which method comprises administering an effective amount of a compound according to any one of claims 1 to 20, wherein the disease, disorder or condition is selected from Parkinson’s Disease or Alzheimer’s Disease.

31. The invention as hereinbefore described.

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