New heterocyclic compounds binding to SLC15a4

Abstract

The present invention relates a compound of formula (I) or a stereoisomer, tautomer, N-oxide, pharmaceutically acceptable salt or solvate thereof. The compounds of formula (I) are useful as medicaments, for use in treatment or prevention of an autoimmune disorder or inflammatory condition. The compound of formula (I) has been demonstrated to inhibit SLC15 peptide transporter-TASL assembly by binding to the SLC15 peptide transporter.

Description

[0001] New heterocyclic compounds binding to SLC15A4

[0002] Field of the Invention

[0003] The present invention relates a compound of formula (I) or a stereoisomer, tautomer, N-oxide, pharmaceutically acceptable salt or solvate thereof. The present invention further relates to a pharmaceutical composition comprising the compound of formula (I) and at least one pharma- ceutically acceptable carrier. The compounds of formula (I) are useful as medicaments, for use in treatment or prevention of an autoimmune disorder or inflammatory condition, in particular an autoimmune disorder being systemic lupus erythematosus, or an inflammatory condition selec- ted from inflammatory bowel disease, psoriasiform dermatitis, and endosomal TLR-dependent inflammation. Preferably, the autoimmune disorder to be treated with the compound of formula (I) is a disorder associated with SLC15 peptide transporter. The compound of formula (I) has been demonstrated to bind SLC15 peptide transporter.

[0004] Background of the Invention

[0005] Dysregulation of pathogen-recognition pathways of the innate immune system is associated with multiple autoimmune and inflammatory disorders. Recognition of pathogen-derived nucleic acids by pattern recognition receptors is essential to mount protective innate immune responses (E. Bartok, G. Hartmann, Immune Sensing Mechanisms that Discriminate Self from Altered Self and Foreign Nucleic Acids. Immunity 53, 54-77 (2020); A. Ablasser, Z. J. Chen, cGAS in action: Expanding roles in immunity and inflammation. Science 363, (2019); N. A. Lind, V. E. Rael, K. Pestal, B. Liu, G. M. Barton, Regulation of the nucleic acid-sensing Toll-like receptors. Nat Rev Immunol 22, 224-235 (2022)). Despite tight regulatory mechanisms, aberrant activation of these pathways by endogenous ligands or mutations in key regulatory components lead to excessive responses that are causatively linked to several autoimmune and inflammatory conditions (K. Pelka, T. Shibata, K. Miyake, E. Latz, Nucleic acid-sensing TLRs and autoimmunity: novel in- sights from structural and cell biology. Immunol Rev 269, 60-75 (2016); Y. J. Crow, D. B. Stet- son, The type I interferonopathies: 10 years on. Nat Rev Immunol 22, 471-483 (2022)). In par- ticular, sensing of nucleic acids by endolysosomal TLRs is thought to have a critical role in the pathogenesis of systemic lupus erythematosus (SLE) and related autoimmune diseases as well as inflammatory disorders (G. J. Brown et al., TLR7 gain-of-function genetic variation causes human lupus. Nature 605, 349-356 (2022); S. Fillatreau, B. Manfroi, T. Dorner, Toll-like receptor signalling in B cells during systemic lupus erythematosus. Nat Rev Rheumatol 17, 98-108 (2021); G. C. Tsokos, M. S. Lo, P. Costa Reis, K. E. Sullivan, New insights into the immuno- pathogenesis of systemic lupus erythematosus. Nat Rev Rheumatol 12, 716-730 (2016)). Both human genetic and mouse studies have unequivocally identified the lysosomal solute carrier SLC15A4 and transcription factor IRF5 as components essential for mediating disease develop- ment downstream of TLRs (T. Ban, G. R. Sato, T. Tamura, Regulation and role of the transcrip- tion factor IRF5 in innate immune responses and systemic lupus erythematosus. Int Immunol 30, 529-536 (2018); J. Bentham et al., Genetic association analyses implicate aberrant regula- tion of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythem- atosus. Nat Genet 47, 1457-1464 (2015); A. L. Blasius et al., Slc15a4, AP-3, and Hermansky- Pudlak syndrome proteins are required for Toll-like receptor signaling in plasmacytoid dendritic cells (pDC). Proc Natl Acad Sci U S A 107, 19973-19978 (2010); T. Kobayashi et al., The histid- ine transporter SLC15A4 coordinates mTOR-dependent inflammatory responses and patho- genic antibody production. Immunity 41 , 375-388 (2014); R. R. Graham et al., A common haplo- type of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus. Nat Genet 38, 550-555 (2006); A. Katewa et al., The peptide symporter SLC15a4 is essential for the development of systemic lupus eryth- ematosus in murine models. PLoS One 16, e0244439 (2021); H. Almuttaqi, I. A. Udalova, Ad- vances and challenges in targeting IRF5, a key regulator of inflammation. FEBS J 286, 1624- 1637 (2019); S. Song et al., Inhibition of IRF5 hyperactivation protects from lupus onset and severity. J Clin Invest 130, 6700-6717 (2020); T. Ban et al., Genetic and chemical inhibition of IRF5 suppresses pre-existing mouse lupus-like disease. Nat Commun 12, 4379 (2021), Z. Wang et al., An autoimmune pleiotropic SNP modulates IRF5 alternative promoter usage through ZBTB3-mediated chromatin looping. Nat Commun 14, 3430 (2023)). The recently dis- covered protein TASL, encoded by an SLE-associated gene previously known as CXorf21 , is a SLC15A4 interactor essential for IRF5 activation (Bentham et al., 2015; L. X. Heinz et al., TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9. Nature 581 , 316-322 (2020); C. A. Odhams et al., Interferon inducible X-linked gene CXorf21 may contribute to sexual di- morphism in Systemic Lupus Erythematosus. Nat Commun 10, 2164 (2019), Zhang et al, SLC15A4 controls endolysosomal TLR7-9 responses by recruiting the innate immune adaptor TASL. Nat Commun 42(8), 112916 (2023)). Through a C-terminal pLxlS motif, TASL acts as signaling adaptor mediating recruitment of IRF5, in analogy to the key immune adaptors MAVS, STING and TRIF for IRF3 (Heinz et al., 2020; S. Liu et al., Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science 347, aaa2630 (2015)). Thus, TASL represents the fourth, central element in a pathway in which each compon- ent is associated with autoimmune disorders, in particular SLE, providing an unusually strong case and rationale for therapeutic intervention. Interfering with SLC15A4-TASL complex forma- tion has been shown to abolish TLR-induced IRF5 activation, suggesting that this pathway can be targeted with high specificity in order to treat diseases linked thereto.

[0006] Here we describe the identification of compounds, which interfere with the signaling from TLR (in particular TLR7 / 8) to IRF5, and as a result, interfere with IRF5 activation. More specifically, these compounds interfere with the assembly of the SLC15A4-TASL module, leading to efficient degradation of TASL and ablation of IRF5 activation. Consequently, these compounds block en- dolysosomal TLR-induced responses in disease-relevant human immune cells.

[0007] Objects and Summary of the Invention

[0008] The present inventors have demonstrated that targeting of an endolysosomal signaling com- plex by a compound inhibits a disease- (in particular an SLE-) associated proinflam matory path- way. The present inventors have found that chemical intervention with the compound of formula (I) leads to efficient degradation of TASL. Without wishing to be bound by theory, the present in- ventors have demonstrated that TASL is regulated by proteostatic interaction with SLC15A4. Accordingly, interfering with complex formation alone has been shown to lead to efficient de- gradation of TASL. Accordingly, the present invention is based at least in part on the discovery that exploiting this property may be advantageous for chemical targeting of TASL.

[0009] Accordingly, the present invention provides a SLC15A4 binder, which disrupts the SLC15A4- TASL complex, thus interfering with TASL levels and as a consequence interfering with IRF5 activation.

[0010] The invention will be summarized in the following embodiments.

[0011] In a first embodiment, the present invention relates to a compound of formula (I) 3 or a stereoisomer, tautomer, N-oxide, pharmaceutically acceptable salt or solvate thereof, wherein: R1is phenyl substituted with one or more RS1; wherein each RS1is independently selected from -Hal, C1-6alkyl, C1-6haloalkyl, -cycloalkyl, -O(C1-6alkyl), -O(C1-6haloalkyl), and -NH-CO(C1-6alkyl); or two RS1together form a fused hete- rocycloalkyl or heteroaryl moiety;A is a moiety selected from wherein the wavy line in each case marks the connection to the remainder of the molecule;and wherein:R2is C2-4alkylene or C6cycloalkylene, each optionally substituted with one or more RS2; wherein each RS2is independently selected from -OH, -F, and -CH3; or two RS2together form =O;each R3 is independently selected from -H, C1-5 alkyl, -(C0-3 alkylene)-cycloalkyl, -(C0-3 alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-heteroaryl, each optionally substituted with one or more RS3; provided that not both R3are -H; or the two R3together with the nitrogen atom to which they are attached form a heterocycloalkyl ring, optionally substitutS3S3ed with one or more R ;wherein each R is independently selected from -CN, -Hal, -OH, -NH2, -NH(C1-6 alkyl), -N(C1-6alkyl)(C1-6alkyl), C1-6alkyl, C1-6haloalkyl, -(C1-6alkylene)-CN, -(C1-6alkylene)-OH, -(C1-6alky- lene)-NH(C1-6alkyl), -(C1-6alkylene)-N(C1-6alkyl)(C1-6alkyl), -O(C1-6alkyl), -O(C1-6haloalkyl), -(C1-6alkylene)-O(C1-6alkyl), -S(C1-6alkyl), -S(C1-6haloalkyl), -(C1-6alkylene)-S(C1-6alkyl), -COH, -CO(C1-6alkyl), -CO(cycloalkyl), -CO(heterocycloalkyl), -COOH, -COO(C1-6alkyl), -CO-NH2,-CO-NH(C1-6 alkyl), -CO-N(C1-6 alkyl)(C1-6 alkyl), -NH-CO(C1-6 alkyl), -N(C1-6 alkyl)-CO(C1-6 alkyl),-S(O)2-(C1-6alkyl), -S(O)2-NH2, -S(O)2-NH(C1-6alkyl), -S(O)2-N(C1-6alkyl)(C1-6alkyl), -NH-S(O)2- (C1-6alkyl), -N(C1-6alkyl)-S(O)2-(C1-6alkyl), -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocy- cloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-heteroaryl, wherein in said alkylene moiety of said -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-heteroaryl one -CH2- group if present is optionally replaced by -O-, and wherein thecycloalkyl moiety in said -(C0-3alkylene)-cycloalkyl, the heterocycloalkyl moiety in said -(C0-3alkylene)-heterocycloalkyl, the aryl moiety in said -(C0-3alkylene)-aryl, and the heteroaryl moiety in said -(C0-3alkylene)-heteroaryl are each optionally substituted with one or more groups each independently selected from -Hal, C1-2alkyl, C1-2haloalkyl, -O(C1-2alkyl), and -O(C1-2haloalkyl);or two RS3 attached to the same carbon atom form =O; or, if attached to a heterocycloalkyl ringformed by two R3together with the nitrogen atom to which they are attached, two RS3together with two neighboring atoms to which they are attached form a fused heteroaryl ring; R4is absent or C1-45alkylene;R is -H, -Hal, -OH, C1-6 alkyl, or -O(C1-6 alkyl); R6is C1-6alkyl, C1-6haloalkyl, -(C1-6alkylene)-OH, -(C1-6alkylene)-O(C1-6alkyl), -(C1-6alky- lene)-N(C1-6alkyl)(C1-6alkyl), -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, or -(C0-3alkylene)-heteroaryl, wherein in said alkylene moiety of said -(C0-3alky- lene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-het-eroaryl one -CH2- group if present is optionally replaced by -O-, and wherein the cycloalkyl moi-ety in said -(C0-3alkylene)-cycloalkyl, the heterocycloalkyl moiety in said -(C0-3alkylene)-hetero- cycloalkyl, the aryl moiety in said -(C0-3alkylene)-aryl and the heteroaryl moiety in said -(C0-3alkylene)-heteroaryl are each optionally substituted with one or more groups each indepen- dently selected from -Hal, C1-2alkyl, C1-2haloalkyl, and -O(C1-2alkyl); X1is CH or N; X2is CH or N; Y1is CRY1or N; Y23 is CRY2or RYN;Y is C 3 or N;Y4is CRY4or N; wherein RY1, RY2, RY3, and RY4are each independently selected from -H, -CN, -Hal, -OH, -NH2, C1-6alkyl, C1-6haloalkyl, -O(C1-6alkyl), -O(C1-6haloalkyl), and -(C1-6alkylene)-O(C1-6alkyl); provided that if X1and X2are both CH, at least one of Y1, Y2, Y3, a4rovided that if X2 is N, one of X1nd Y is N; andp , Y1, Y2, Y3, and Y4 is also N; andprovided that not more than two of X1, X2, Y1, Y2, Y3, and Y4are N. In connection with the above definitions, in particular the definitions of R3, RS3, and R6, cycloalkyl preferably refers to C3-7cycloalkyl, heterocycloalkyl preferably refers to 3- to 7-membered heterocycloalkyl, wherein the heterocy-cloalkyl ring comprises one or more ring heteroatoms independently selected from O, S and N, wherein the one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, aryl preferably refers to phenyl, and heteroaryl preferably refers to (5- or 6-membered heteroaryl), wherein the heteroaryl ring com-prises one or more ring heteroatoms independently selected from O, S and N, wherein the one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized. In a preferred embodiment, the present invention relates to a compound of formula (I) or a stereoisomer, tautomer, N-oxide, pharmaceutically acceptable salt or solvate thereof,wherein:R1is phenyl substituted with one or more RS1; wherein each RS1is independently selected from -Hal, C1-6alkyl, C1-6haloalkyl, -cycloalkyl, -O(C1-6alkyl), -O(C1-6haloalkyl), and -NH-CO(C1-6alkyl); or two RS1together form a fused hete-rocycloalkyl or heteroaryl moiety;A is a moiety selected from wherein the wavy line in each case marks the connection to the remainder of the molecule; and wherein: R2is C2-4alkylene or C6cycloalkylene, each optionally substituted with one or more RS2; wherein each RS2is independently selected from -OH, -F, and -CH3; or two RS2together form =O; each R3is independently selected from -H, C1-5alkyl, -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3 alkylene)-aryl, and -(C0-3 alkylene)-heteroaryl, each optionally substitutedwith one or more RS3; provided that not both R3are -H; or the two R3together with the nitrogen atom to which they are attached form a heterocycloalkyl ing, optionally substituted with one or more RS3; wherein each RS3is independently selected from -CN, -Hal, -OH, -NH2, -NH(C1-6alkyl), -N(C1-6alkyl)(C1-6 alkyl), C1-6 alkyl, C1-6 haloalkyl, -(C1-6 alkylene)-CN, -(C1-6 alkylene)-OH, -(C1-6 alky-ene)-NH(C1-6alkyl), -(C1-6alkylene)-N(C1-6alkyl)(C1-6alkyl), -O(C1-6alkyl), -O(C1-6haloalkyl), (C1-6alkylene)-O(C1-6alkyl), -S(C1-6alkyl), -S(C1-6haloalkyl), -(C1-6alkylene)-S(C1-6alkyl), -COH, CO(C1-6alkyl), -CO(cycloalkyl), -CO(heterocycloalkyl), -COOH, -COO(C1-6alkyl), -CO-NH2, CO-NH(C1-6alkyl), -CO-N(C1-6alkyl)(C1-6alkyl), -NH-CO(C1-6alkyl), -N(C1-6alkyl)-CO(C1-6alkyl), S(O)2-(C1-6 alkyl), -S(O)2-NH2, -S(O)2-NH(C1-6 alkyl), -S(O)2-N(C1-6 alkyl)(C1-6 alkyl), -NH-S(O)2-C1-6alkyl), -N(C1-6alkyl)-S(O)2-(C1-6alkyl), -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocy- cloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-heteroaryl, wherein in said alkylene moiety of said -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-heteroaryl one -CH2- group if present is optionally replaced by -O-, and wherein thecycloalkyl moiety in said -(C0-3 alkylene)-cycloalkyl, the heterocycloalkyl moiety in said -(C0-3alkylene)-heterocycloalkyl, the aryl moiety in said -(C0-3alkylene)-aryl, and the heteroaryl moietyn said -(C0-3alkylene)-heteroaryl are each optionally substituted with one or more groups eachndependently selected from -Hal, C1-2alkyl, C1-2haloalkyl, -O(C1-2alkyl), and -O(C1-2haloalkyl); or two RS3attached to the same carbon atom form =O; or, if attached to a heterocycloalky dby two R3l ringorme together with the nitrogen atom to which they are attached, two RS3 togetherwith two neighboring atoms to which they are attached form a fused heteroaryl ring; R4is absent or C1-4alkylene; R5is -Hal, -OH, C1-6alkyl, or -O(C1-66alkyl);R is C1-6 alkyl, C1-6 haloalkyl, -(C1-6 alkylene)-OH, -(C1-6 alkylene)-O(C1-6 alkyl), -(C1-6 alky-ene)-N(C1-6alkyl)(C1-6alkyl), -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, or -(C0-3alkylene)-heteroaryl, wherein in said alkylene moiety of said -(C0-3alky-ene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-het- eroaryl one -CH2- group if present is optionally replaced by -O-, and wherein the cycloalkyl moi-ety in said -(C0-3 alkylene)-cycloalkyl, the heterocycloalkyl moiety in said -(C0-3 alkylene)-hetero-cycloalkyl, the aryl moiety in said -(C0-3alkylene)-aryl and the heteroaryl moiety in said -(C0-3alkylene)-heteroaryl are each optionally substituted with one or more groups each indepen- dently selected from -Hal, C1-2alkyl, C1-2haloalkyl, and -O(C1-2alkyl);X1 is CH or N;X2is CH or N; Y1is CRY1or N; Y2is CRY2or N; Y34 is CRY3Y4or N;Y is CR or N;wherein RY1, RY2, RY3, and RY4are each independently selected from -H, -CN, -Hal, -OH, -NH2, C1-6alkyl, C1-6haloalkyl, -O(C1-6alkyl), -O(C1-6haloalkyl), and -(C1-6alkylene)-O(C1-6alkyl); provided that if X1and X2are both CH, at least one of Y1, Y2, Y3, and Y4is N; and 6 provided that if X2is N, one of X1, Y1, Y2, Y3, and Y4is also N; and provided that not more than two of X1, X2, Y1, Y2, Y3, and Y4are N. In one preferred embodiment of the compound of formula (I), RY1, RY2, RY3, and RY4are eachindependently selected from -H, -CN, -Hal, -OH, C1-6 alkyl, C1-6 haloalkyl, -O(C1-6 alkyl), -O(C1-6haloalkyl), and -(C1-6alkylene)-O(C1-6alkyl). In one preferred embodiment, the compound of formula (I) is a compound of formula (Ia), (Ib), (Ic), (Id), (Ie), or (If) pr In another preferred embodiment, the compound of formula (I) is a compound of formula (Ia), (Ib), (Ic), (Id), or (Ie) In a more preferred embodiment, the compound of formula (I) is a compound of formula (Ia), (Ib), (Ic), (Id), or (Ie) wherein , , , , , Hal, -OH, C1-6alkyl, C1-6haloalkyl, -O(C1-6alkyl), -O(C1-6haloalkyl), and -(C1-6alkylene)-O(C1-6alkyl). In another more preferred embodiment, the compound of formula (I) is a compound of formula(Ia), (Ib), or (Ic)

[0012] In another more preferred embodiment, the compound of formula (I) is a compound of formula (la*), (lb*), or (lc*)

[0013] In one particularly preferred embodiment, the compound of formula (I) is a compound of for- mula (la*) In one particularly preferred embodiment, the compound of formula (I) is a compound of for- mula (lb*)

[0014] In one particularly preferred embodiment, the compound of formula (I) is a compound of for- mula (lc*)

[0015] In another preferred embodiment, R1is phenyl substituted with -O(C1.6alkyl).

[0016] In a more preferred embodiment, R1is 4-ethoxyphenyl.

[0017] In another preferred embodiment, the moiety A is wherein R2is C2alkylene or C3alkylene. In another preferred embodiment, the moiety A is wherein each R3is independently selected from -H, C1-5alkyl, -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)- heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-heteroaryl, each optionally substituted with one or moreS3S3R ;wherein each R is independently selected from -CN, -Hal, -OH, NH2, -NH(C1-6 alkyl), -N(C1-6alkyl)(C1-6alkyl), C1-6alkyl, C1-6haloalkyl, -(C1-6alkylene)-CN, -(C1-6alkylene)-OH, -O(C1-6alkyl), -(C1-6alkylene)-O-(C1-6alkyl), -CO(C1-6alkyl), -CO(cycloalkyl), -CO(heterocycloalkyl), -CO-NH2, -CO-NH(C1-6alkyl), -CO-N(C1-6alkyl)(C1-6alkyl), -NH-CO(C1-6alkyl), -S(O)2-(C1-6alkyl), -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-heteroaryl, wherein in said alkylene moiety of said -(C0-3 alkylene)-cycloalkyl, -(C0-3 alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl and -(C0-3alkylene)-heteroaryl one -CH2- group if present is optionally replaced by -O-, and wherein the cycloalkyl moiety in said -(C0-3alkylene)-cy- cloalkyl, the heterocycloalkyl moiety in said -(C0-3alkylene)-heterocycloalkyl, the aryl moiety in said -(C0-3alkylene)-aryl and the heteroaryl moiety in said -(C0-3alkylene)-heteroaryl are eachoptionally substituted with one or more groups each independently selected from -Hal, C1-2 alkyl,C1-2haloalkyl, and -O(C1-2alkyl); or two RS3attached to the same carbon atom form =O. In another preferred embodiment, the moiety A is whereinthe two R3together with the nitrogen atom to which they are attached form a heterocycloalkyl ring, optionally substituted with one or more RS3; wherein each RS3is independently selected from -CN, -Hal, -OH, NH2, -NH(C1-6alkyl), -N(C1-6alkyl)(C1-6alkyl), C1-6alkyl, C1-6haloalkyl, -(C1-6alkylene)-CN, -(C1-6alkylene)-OH, -O(C1-6alkyl),-(C1-6 alkylene)-O-(C1-6 alkyl), -CO(C1-6 alkyl), -CO(cycloalkyl), -CO(heterocycloalkyl), -CO-NH2,-CO-NH(C1-6alkyl), -CO-N(C1-6alkyl)(C1-6alkyl), -NH-CO(C1-6alkyl), -S(O)2-(C1-6alkyl), -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)- heteroaryl, wherein in said alkylene moiety of said -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)- heterocycloalkyl, -(C0-3alkylene)-aryl and -(C0-3alkylene)-heteroaryl one -CH2- group if presentis optionally replaced by -O-, and wherein the cycloalkyl moiety in said -(C0-3 alkylene)-cy-cloalkyl, the heterocycloalkyl moiety in said -(C0-3alkylene)-heterocycloalkyl, the aryl moiety in said -(C0-3alkylene)-aryl and the heteroaryl moiety in said -(C0-3alkylene)-heteroaryl are each optionally substituted with one or more groups each independently selected from -Hal, C1-2alkyl, C1-2haloalkyl, and -O(C1-2alkyl);or two RS3 attached to the same carbon atom form =O; or two RS3 together with two neighboringatoms to which they attached form a fused heteroaryl ring. In another preferred embodiment, the moiety A is . In a particularly preferred embodiment, the compound is a compound selected from the follow-ing compounds or a stereoisomer, tautomer, N-oxide, pharmaceutically acceptable salt or sol-vate thereof:

[0018]

[0019] 5 In another particularly preferred embodiment, the compound is a compound selected from the following compounds or a stereoisomer, tautomer, N-oxide, pharmaceutically acceptable salt or solvate thereof:

[0020]

[0021] In another particularly preferred embodiment, the compound is a compound selected from the

[0022] 5 following compounds or a stereoisomer, tautomer, N-oxide, pharmaceutically acceptable salt or solvate thereof:

[0023]

[0024] In a second embodiment, the present invention relates to a pharmaceutical composition com- prising the compound of formula (I) or a stereoisomer, tautomer, N-oxide, pharmaceutically ac- ceptable salt or solvate thereof, and at least one pharmaceutically acceptable carrier.

[0025] In a third embodiment, the present invention relates to the compound of formula (I) or a stereoisomer, tautomer, N-oxide, pharmaceutically acceptable salt or solvate thereof, or to the pharmaceutical composition of the present invention for use as a medicament.

[0026] In a fourth embodiment, the present invention relates to the compound of formula (I) or a stereoisomer, tautomer, N-oxide, pharmaceutically acceptable salt or solvate thereof, or to the pharmaceutical composition of the present invention for use in treatment or prevention of an autoimmune disorder or inflammatory condition.

[0027] In a fifth embodiment, the present invention relates to use of the compound of formula (I) or a stereoisomer, tautomer, N-oxide, pharmaceutically acceptable salt or solvate thereof, or the pharmaceutical composition of the present invention in the manufacture of a medicament for treatment or prevention of an autoimmune disorder or inflammatory condition.

[0028] In a sixth embodiment, the present invention relates to a method of treatment of an autoim- mune disorder or inflammatory condition, the method comprising administering the compound of formula (I) or a stereoisomer, tautomer, N-oxide, pharmaceutically acceptable salt or solvate thereof, or the pharmaceutical composition of the present invention, to the subject in need thereof. It is to be understood that a therapeutically effective amount of the compound of for- mula (I) or a stereoisomer, tautomer, N-oxide, pharmaceutically acceptable salt or solvate thereof, or the pharmaceutical composition of the present invention, is to be administered.

[0029] Brief Description of the Figures Figure 1 : Example of TCG reporter assay data showing TASL-EmGFP (upper part) and mCh- erry (lower part) signals upon compound treatment (in the present case Example I c-8, which was used at three different concentrations as indicated).

[0030] Figure 2: Binding of Probel to SLC15A4 as measured by the NanoBRET assay as outlined herein in biological example 2.

[0031] Definitions

[0032] The following definitions apply throughout the present specification and the claims, unless specifically indicated otherwise.

[0033] The term “hydrogen” is herein used to refer to protium, deuterium and / or tritium, preferably to protium. Accordingly, the term “non-hydrogen atom” refers to any atom that is not hydrogen, i.e. that is not protium, deuterium or tritium.

[0034] The term “hydrocarbon group” refers to a group consisting of carbon atoms and hydrogen atoms.

[0035] The term “alicyclic” is used in connection with cyclic groups and denotes that the correspond- ing cyclic group is non-aromatic.

[0036] As used herein, the term “alkyl” refers to a monovalent saturated acyclic (i.e., non-cyclic) hy- drocarbon group which may be linear or branched. Accordingly, an “alkyl” group does not com- prise any carbon-to-carbon double bond or any carbon-to-carbon triple bond. A “C-,.5 alkyl” de- notes an alkyl group having 1 to 5 carbon atoms. Preferred exemplary alkyl groups are methyl, ethyl, propyl (e.g., n-propyl or isopropyl), or butyl (e.g., n-butyl, isobutyl, sec-butyl, or tert-butyl). Unless defined otherwise, the term “alkyl” preferably refers to Ci.4alkyl, more preferably to methyl or ethyl, and even more preferably to methyl.

[0037] As used herein, the term “alkenyl” refers to a monovalent unsaturated acyclic hydrocarbon group which may be linear or branched and comprises one or more (e.g., one or two) carbon-to- carbon double bonds while it does not comprise any carbon-to-carbon triple bond. The term “C2.5alkenyl” denotes an alkenyl group having 2 to 5 carbon atoms. Preferred exemplary alkenyl groups are ethenyl, propenyl (e.g., prop-1 -en-1-yl, prop-1 -en-2-yl, or prop-2-en-1-yl), butenyl, butadienyl (e.g., buta-1 ,3-dien-1-yl or buta-1 ,3-dien-2-yl), pentenyl, or pentadienyl (e.g., iso- prenyl). Unless defined otherwise, the term “alkenyl” preferably refers to C2.4 alkenyl.

[0038] As used herein, the term “alkynyl” refers to a monovalent unsaturated acyclic hydrocarbon group which may be linear or branched and comprises one or more (e.g., one or two) carbon-to- carbon triple bonds and optionally one or more (e.g., one or two) carbon-to-carbon double bonds. The term “C2.5alkynyl” denotes an alkynyl group having 2 to 5 carbon atoms. Preferred exemplary alkynyl groups are ethynyl, propynyl (e.g., propargyl), or butynyl. Unless defined oth- erwise, the term “alkynyl” preferably refers to C2.4alkynyl.

[0039] As used herein, the term “alkylene” refers to an alkanediyl group, i.e. a divalent saturated acyclic hydrocarbon group which may be linear or branched. A “C-,.5 alkylene” denotes an alky- lene group having 1 to 5 carbon atoms, and the term “C0.3alkylene” indicates that a covalent bond (corresponding to the option “Coalkylene”) or a C-|.3alkylene is present. Preferred exem- plary alkylene groups are methylene (-CH2-), ethylene (e.g., -CH2-CH2- or -CH(-CH3)-), propy- lene (e.g., -CH2-CH2-CH2-, -CH(-CH2-CH3)-, -CH2-CH(-CH3)-, or -CH(-CH3)-CH2-), or butylene (e.g., -CH2-CH2-CH2-CH2-). Unless defined otherwise, the term “alkylene” preferably refers to C14alkylene (including, in particular, linear Ci.4alkylene), more preferably to methylene or eth- ylene, and even more preferably to methylene.

[0040] As used herein, the term “carbocyclyl” refers to a hydrocarbon ring group, including mono- cyclic rings as well as bridged ring, spiro ring and / or fused ring systems (which may be com- posed, e.g., of two or three rings), wherein said ring group may be saturated, partially unsatu- rated (i.e., unsaturated but not aromatic) or aromatic. Unless defined otherwise, “carbocyclyl” preferably refers to aryl, cycloalkyl or cycloalkenyl.

[0041] As used herein, the term “heterocyclyl” refers to a ring group, including monocyclic rings as well as bridged ring, spiro ring and / or fused ring systems (which may be composed, e.g., of two or three rings), wherein said ring group comprises one or more (such as, e.g., one, two, three, or four) ring heteroatoms independently selected from O, S and N, and the remaining ring atoms are carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, wherein one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group), and further wherein said ring group may be saturated, partially unsaturated (i.e., unsaturated but not aromatic) or aromatic. For example, each heteroatom-containing ring comprised in said ring group may contain one or two O atoms and / or one or two S atoms (which may optionally be oxidized) and / or one, two, three or four N atoms (which may optionally be oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1 to 4 and that there is at least one carbon ring atom (which may optionally be oxidized) in the corresponding heteroatom-containing ring. Un- less defined otherwise, “heterocyclyl” preferably refers to heteroaryl, heterocycloalkyl or hetero- cycloalkenyl.

[0042] As used herein, the term “aryl” refers to an aromatic hydrocarbon ring group, including mono- cyclic aromatic rings as well as bridged ring and / or fused ring systems containing at least one aromatic ring (e.g., ring systems composed of two or three fused rings, wherein at least one of these fused rings is aromatic; or bridged ring systems composed of two or three rings, wherein at least one of these bridged rings is aromatic). “Aryl” may, e.g., refer to phenyl, naphthyl, di- alinyl (i.e., 1 ,2-dihydronaphthyl), tetralinyl (i.e., 1 ,2,3,4-tetrahydronaphthyl), indanyl, indenyl (e.g., 1 H indenyl), anthracenyl, phenanthrenyl, 9H-fluorenyl, or azulenyl. Unless defined other- wise, an “aryl” preferably has 6 to 14 ring atoms, more preferably 6 to 10 ring atoms, even more preferably refers to phenyl or naphthyl, and most preferably refers to phenyl.

[0043] As used herein, the term “heteroaryl” refers to an aromatic ring group, including monocyclic aromatic rings as well as bridged ring and / or fused ring systems containing at least one aro- matic ring (e.g., ring systems composed of two or three fused rings, wherein at least one of these fused rings is aromatic; or bridged ring systems composed of two or three rings, wherein at least one of these bridged rings is aromatic), wherein said aromatic ring group comprises one or more (such as, e.g., one, two, three, or four) ring heteroatoms, which are preferably indepen- dently selected from O, S and N, and the remaining ring atoms are carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, and further wherein one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group). For example, each heteroatom-containing ring comprised in said aromatic ring group may contain one or two O atoms and / or one or two S atoms (which may optionally be oxidized) and / or one, two, three or four N atoms (which may optionally be oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1 to 4 and that there is at least one carbon ring atom (which may optionally be oxidized) in the corre- sponding heteroatom-containing ring. “Heteroaryl” may, e.g., refer to thienyl (i.e., thiophenyl), benzo[b]thienyl, naphtho[2,3-b]thienyl, thianthrenyl, furyl (i.e., furanyl), benzofuranyl, isobenzo- furanyl, chromanyl, chromenyl (e.g., 2H-1 -benzopyranyl or 4H-1-benzopyranyl), isochromenyl (e.g., 1 H-2-benzopyranyl), chromonyl, xanthenyl, phenoxathiinyl, pyrrolyl (e.g., 1 H-pyrrolyl), imi- dazolyl, pyrazolyl, pyridyl (i.e., pyridinyl; e.g., 2-pyridyl, 3-pyridyl, or 4-pyridyl), pyrazinyl, pyrim- idinyl, pyridazinyl, indolyl (e.g., 3H-indolyl), isoindolyl, indazolyl, indolizinyl, purinyl, quinolyl, iso- quinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, cinnolinyl, pteridinyl, carbazolyl, p-carbolinyl, phenanthridinyl, acridinyl, perimidinyl, phenanthrolinyl (e.g., [1 ,10]phenanthrolinyl, [1 ,7]phenan- throlinyl, or [4,7]phenanthrolinyl), phenazinyl, thiazolyl, isothiazolyl, phenothiazinyl, oxazolyl, isoxazolyl, oxadiazolyl (e.g., 1 ,2,4-oxadiazolyl, 1 ,2,5-oxadiazolyl (i.e., furazanyl), or 1 ,3,4-oxadi- azolyl), thiadiazolyl (e.g., 1 ,2,4-thiadiazolyl, 1 ,2,5-thiadiazolyl, or 1 ,3,4-thiadiazolyl), phenox- azinyl, pyrazolo[1 ,5-a]pyrimidinyl (e.g., pyrazolo[1 ,5-a]pyrimidin-3-yl), 1 ,2-benzoisoxazol-3-yl, benzothiazolyl, benzothiadiazolyl, benzoxazolyl, benzisoxazolyl, benzimidazolyl, benzo[b]thio- phenyl (i.e., benzothienyl), triazolyl (e.g., 1 H-1 ,2,3-triazolyl, 2H-1 ,2,3-triazolyl, 1 H-1 ,2,4-triazolyl, or 4H-1 ,2,4-triazolyl), benzotriazolyl, 1 H-tetrazolyl, 2H-tetrazolyl, triazinyl (e.g., 1 ,2,3-triazinyl, 1 ,2,4-triazinyl, or 1 ,3,5-triazinyl), furo[2,3-c]pyridinyl, dihydrofuropyridinyl (e.g., 2,3-dihydro- furo[2,3-c]pyridinyl or 1 ,3-dihydrofuro[3,4-c]pyridinyl), imidazopyridinyl (e.g., imidazo[1 ,2- a]pyridinyl or imidazo[3,2-a]pyridinyl), quinazolinyl, thienopyridinyl, tetrahydrothienopyridinyl (e.g., 4,5,6,7-tetrahydrothieno[3,2-c]pyridinyl), dibenzofuranyl, 1 ,3-benzodioxolyl, benzodioxanyl (e.g., 1 ,3-benzodioxanyl or 1 ,4-benzodioxanyl), or coumarinyl. Unless defined otherwise, the term “heteroaryl” preferably refers to a 5 to 14 membered (more preferably 5 to 10 membered) monocyclic ring or fused ring system comprising one or more (e.g., one, two, three or four) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized; even more preferably, a “heteroaryl” refers to a 5 or 6 membered monocyclic ring comprising one or more (e.g., one, two or three) ring het- eroatoms independently selected from O, S and N, wherein one or more S ring atoms (ifpresent) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein oneor more carbon ring atoms are optionally oxidized. As used herein, the term “cycloalkyl” refers to a saturated hydrocarbon ring group, including monocyclic rings as well as bridged ring, spiro ring and / or fused ring systems (which may be composed, e.g., of two or three rings; such as, e.g., a fused ring system composed of two orthree fused rings). “Cycloalkyl” may, e.g., refer to cyclopropyl, cyclobutyl, cyclopentyl, cyclo-hexyl, cycloheptyl, decalinyl (i.e., decahydronaphthyl), or adamantyl. Unless defined otherwise, “cycloalkyl” preferably refers to a C3-11cycloalkyl, and more preferably refers to a C3-7cycloalkyl. A particularly preferred “cycloalkyl” is a monocyclic saturated hydrocarbon ring having 3 to 7 ring members (e.g., cyclopropyl or cyclohexyl). As used herein, the term “cycloalkylene” refers to a cycloalkanediyl group, i.e. a divalent satu-rated cyclic hydrocarbon group. A “C6cycloalkylene” denotes a cyclohexanediyl group, prefer- ably a cyclohexane-1,4-diyl group. In other words, “C6cycloalkylene” preferably refers to a cy- clohexane unit which is attached to the remainder of the molecule at positions 1 and 4 of the cy- clohexane ring. Unless defined otherwise, the term “cycloalkylene” preferably refers to C3-6cy-cloalkylene (including, in particular, C6 cycloalkylene).As used herein, the term “heterocycloalkyl” refers to a saturated ring group, including mono- cyclic rings as well as bridged ring, spiro ring and / or fused ring systems (which may be com- posed, e.g., of two or three rings; such as, e.g., a fused ring system composed of two or three fused rings), wherein said ring group contains one or more (such as, e.g., one, two, three, orfour) ring heteroatoms independently selected from O, S and N, and the remaining ring atomsare carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, and further wherein one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group). For example, each heteroatom- containing ring comprised in said saturated ring group may contain one or two O atoms and / orone or two S atoms (which may optionally be oxidized) and / or one, two, three or four N atoms(which may optionally be oxidized), provided that the total number of heteroatoms in the corre- sponding heteroatom-containing ring is 1 to 4 and that there is at least one carbon ring atom (which may optionally be oxidized) in the corresponding heteroatom-containing ring. “Heterocy- cloalkyl” may, e.g., refer to aziridinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl,piperidinyl, piperazinyl, azepanyl, diazepanyl (e.g., 1,4-diazepanyl), oxazolidinyl, isoxazolidinyl,thiazolidinyl, isothiazolidinyl, morpholinyl (e.g., morpholin-4-yl), thiomorpholinyl (e.g., thiomor- pholin-4-yl), oxazepanyl, oxiranyl, oxetanyl, tetrahydrofuranyl, 1,3-dioxolanyl, tetrahydropyranyl, 1,4-dioxanyl, oxepanyl, thiiranyl, thietanyl, tetrahydrothiophenyl (i.e., thiolanyl), 1,3-dithiolanyl, thianyl, 1,1-dioxothianyl, thiepanyl, decahydroquinolinyl, decahydroisoquinolinyl, or 2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl. Unless defined otherwise, “heterocycloalkyl” preferably refers to a 3 to11 membered saturated ring group, which is a monocyclic ring or a fused ring system (e.g., a fused ring system composed of two fused rings), wherein said ring group contains one or more (e.g., one, two, three, or four) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) areoptionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized; morepreferably, “heterocycloalkyl” refers to a 5 to 7 membered saturated monocyclic ring group con- taining one or more (e.g., one, two, or three) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxi-dized.As used herein, the term “halogen” or “Hal” refers to fluoro (-F), chloro (-Cl), bromo (-Br), or iodo (-I). As used herein, the term “haloalkyl” refers to an alkyl group substituted with one or more (preferably 1 to 6, more preferably 1 to 3) halogen atoms which are selected independently fromfluoro, chloro, bromo and iodo, and are preferably all fluoro atoms. It will be understood that themaximum number of halogen atoms is limited by the number of available attachment sites and, thus, depends on the number of carbon atoms comprised in the alkyl moiety of the haloalkyl group. “Haloalkyl” may, e.g., refer to -CF3, -CHF2, -CH2F, -CF2-CH3, -CH2-CF3, -CH2-CHF2, -CH2-CF2-CH3, -CH2-CF2-CF3, or -CH(CF3)2. A particularly preferred “haloalkyl” group is -CF3.

[0044] The terms “bond” and “covalent bond” are used herein synonymously, unless explicitly indi- cated otherwise or contradicted by context.

[0045] As used herein, the terms “optional”, “optionally” and “may” denote that the indicated feature may be present but can also be absent. Whenever the term “optional”, “optionally” or “may” is used, the present invention specifically relates to both possibilities, i.e., that the corresponding feature is present or, alternatively, that the corresponding feature is absent. For example, the expression “X is optionally substituted with Y” (or “X may be substituted with Y”) means that X is either substituted with Y or is unsubstituted. Likewise, if a component of a composition is indi- cated to be “optional”, the invention specifically relates to both possibilities, i.e., that the corre- sponding component is present (contained in the composition) or that the corresponding com- ponent is absent from the composition.

[0046] The term "substituted", as used herein, means that a hydrogen atom bonded to a designated atom is replaced with a specified substituent, provided that the substitution results in a stable or chemically feasible compound. Unless otherwise indicated, a substituted atom may have one or more substituents and each substituent is independently selected.

[0047] The term "substitutable", when used in reference to a designated atom, means that attached to the atom is a hydrogen, which can be replaced with a suitable substituent.

[0048] Various groups are referred to as being “optionally substituted” in this specification. Generally, these groups may carry one or more substituents, such as, e.g., one, two, three or four sub- stituents. It will be understood that the maximum number of substituents is limited by the num- ber of attachment sites available on the substituted moiety. Unless defined otherwise, the “op- tionally substituted” groups referred to in this specification carry preferably not more than two substituents and may, in particular, carry only one substituent. Moreover, unless defined other- wise, it is preferred that the optional substituents are absent, i.e. that the corresponding groups are unsubstituted.

[0049] A skilled person will appreciate that the substituent groups comprised in the compounds of the present invention may be attached to the remainder of the respective compound via a number of different positions of the corresponding specific substituent group. Unless defined otherwise, the preferred attachment positions for the various specific substituent groups are as illustrated in the examples.

[0050] As used herein, unless explicitly indicated otherwise or contradicted by context, the terms “a”, “an” and “the” are used interchangeably with “one or more” and “at least one”. Thus, for exam- ple, a composition comprising “a” compound of formula (I) can be interpreted as referring to a composition comprising “one or more” compounds of formula (I).

[0051] It is to be understood that wherever numerical ranges are provided / disclosed herein, all values and subranges encompassed by the respective numerical range are meant to be encompassed within the scope of the invention. Accordingly, the present invention specifically and individually relates to each value that falls within a numerical range disclosed herein, as well as each sub- range encompassed by a numerical range disclosed herein.

[0052] As used herein, the term “about” preferably refers to ±10% of the indicated numerical value, more preferably to ±5% of the indicated numerical value, and in particular to the exact numerical value indicated. If the term “about” is used in connection with the endpoints of a range, it prefer- ably refers to the range from the lower endpoint -10% of its indicated numerical value to the up- per endpoint +10% of its indicated numerical value, more preferably to the range from of the lower endpoint -5% to the upper endpoint +5%, and even more preferably to the range defined by the exact numerical values of the lower endpoint and the upper endpoint.

[0053] As used herein, the term “comprising” (or “comprise”, “comprises”, “contain”, “contains”, or “containing”), unless explicitly indicated otherwise or contradicted by context, has the meaning of “containing, inter alia”, i.e., “containing, among further optional elements, ...”. In addition thereto, this term also includes the narrower meanings of “consisting essentially of” and “con- sisting of’. For example, the term “A comprising B and C” has the meaning of “A containing, inter alia, B and C”, wherein A may contain further optional elements (e.g., “A containing B, C and D” would also be encompassed), but this term also includes the meaning of “A consisting essentially of B and C” and the meaning of “A consisting of B and C” (i.e., no other components than B and C are comprised in A).

[0054] The “treatment” of a disorder or disease may, for example, lead to a halt in the progression of the disorder or disease (e.g., no deterioration of symptoms) or a delay in the progression of the disorder or disease (in case the halt in progression is of a transient nature only). The “treatment” of a disorder or disease may also lead to a partial response (e.g., amelioration of symptoms) or complete response (e.g., disappearance of symptoms) of the subject / patient suffering from the disorder or disease. Accordingly, the “treatment” of a disorder or disease may also refer to an amelioration of the disorder or disease, which may, e.g., lead to a halt in the progression of the disorder or disease or a delay in the progression of the disorder or disease. Such a partial or complete response may be followed by a relapse. It is to be understood that a subject / patient may experience a broad range of responses to a treatment (such as the exemplary responses as described herein above). The treatment of a disorder or disease may, inter alia, comprise cu- rative treatment (preferably leading to a complete response and eventually to healing of the dis- order or disease) and palliative treatment (including symptomatic relief).

[0055] The term “prevention” of a disorder or disease, as used herein, is also well known in the art. For example, a patient / subject suspected of being prone to suffer from a disorder or disease may particularly benefit from a prevention of the disorder or disease. The subject / patient may have a susceptibility or predisposition for a disorder or disease, including but not limited to hereditary predisposition. Such a predisposition can be determined by standard methods or as- says, using, e.g., genetic markers or phenotypic indicators. It is to be understood that a disorder or disease to be prevented in accordance with the present invention has not been diagnosed or cannot be diagnosed in the patient / subject (for example, the patient / subject does not show any clinical or pathological symptoms). Thus, the term “prevention” comprises the use of a com- pound of the present invention before any clinical and / or pathological symptoms are diagnosed or determined or can be diagnosed or determined by the attending physician (or attendant vet- erinarian).

[0056] Detailed Description

[0057] The invention will be described in detail in the following.

[0058] As indicated above, the present invention relates in one embodiment to a compound of for- mula (I) or a stereoisomer, tautomer, N-oxide, pharmaceutically acceptable salt or solvate thereof, wherein the substituents are as defined above. Preferred embodiments of the substituents will be described in detail in the following. It is to be understood that each preferred embodiment is relevant on its own as well as in combination with other preferred embodiments. Furthermore, it is to be understood that the preferred embodiments in each case also apply to the stereoiso- mers, tautomers, N-oxides, pharmaceutically acceptable salts and solvates of the compounds of the invention.

[0059] In one embodiment of the compound of formula (I), X1is CH or N;

[0060] X2is CH or N;

[0061] Y1is CRY1or N;

[0062] Y2is CRY2or N;

[0063] Y3is CRY3or N; Y4is CRY4or N; wherein RY1, RY2, RY3, and RY4are each independently selected from -H, -CN, -Hal, -OH, -NH2, C1-6alkyl, C1-6haloalkyl, -O(C1-6alkyl), -O(C1-6haloalkyl), and -(C1-6alkylene)-O(C1-6alkyl); provided that if X1 2 1 2 3 4ded that if X2and X are bo is N, one of X1th C ,Y1H, at least one of Y , Y, Y , and Y is N; andprovi , Y2, Y3, and Y4 is also N; andprovided that not more than two of X1, X2, Y1, Y2, Y3, and Y4are N. In a preferred embodiment, RY1, RY2, RY3, and RY4are each independently selected from -H, - CN, -Hal, C1-6alkyl, C1-6haloalkyl, -O(C1-6alkyl), and -O(C1-6haloalkyl). In a more preferred embodiment, RY1, RY2, RY3, and RY4are each independently selected from-H, -Hal, C1 alkyl, C1 haloalkyl, -O(C1 alkyl), and -O(C1 haloalkyl).In an even more preferred embodiment, RY1, RY2, RY3, and RY4are each independently se- lected from -H, -Hal, C1alkyl, and C1haloalkyl. In a particularly preferred embodiment, RY1, RY2, RY3, and RY4are each independently selected from -H, -Cl, -F, and -CH3. In another embodiment, X1is CH or N; X2is CH or N; Y1 Y12 is CR ;Y is CRY2 or N;Y3is CRY3or N; Y4is CRY4or N; wherein RY1, RY2, RY3, and RY4are each independently selected from -H, -CN, -Hal, -OH, -NH2, C1-6alkyl, C1-6haloalkyl, -O(C1-6alkyl), -O(C1-6haloalkyl), and -(C1-6alkylene)-O(C1-6alkyl);provided that if X1 and X2 are both CH, at least one of Y1, Y2, Y3, and Y4 is N; andprovided that if X2is N, one of X1, Y1, Y2, Y3, and Y4is also N; and provided that not more than two of X1, X2, Y1, Y2, Y3, and Y4are N. In a preferred embodiment, RY1, RY2, RY3, and RY4are each independently selected from -H, -CN, -Hal, -OH, C1-6alkyl, C1-6haloalkyl, -O(C1-6alkyl), -O(C1-6haloalkyl), and -(C1-6alkylene)-O(C1-6 alkyl).In a preferred embodiment, RY1, RY2, RY3, and RY4are each independently selected from -H, - CN, -Hal, C1-6alkyl, C1-6haloalkyl, -O(C1-6alkyl), and -O(C1-6haloalkyl). In a more preferred embodiment, RY1, RY2, RY3, and RY4are each independently selected from -H, -Hal, C1alkyl, C1haloalkyl, -O(C1alkyl), and -O(C1haloa eferred embodiment, RY1, RY2, RY3lkyl). In an even more pr , and RY4 are each independently se-lected from -H, -Hal, C1alkyl, and C1haloalkyl. In a particularly preferred embodiment, RY1, RY2, RY3, and RY4are each independently selected from -H, -Cl, -F, and -CH3. In one embodiment, the compound of formula (I) is a compound of formula (Ia), (Ib), (Ic), (Id),(Ie), or (If) In a preferred embodiment, the compound of formula (I) is a compound of formula (Ia), (Ib), (Ic), (Id), or (Ie). Also in connection with the compounds of formula (Ia), (Ib), (Ic), (Id), (Ie), andY1 Y2 Y3Y4(If), R , R , R ,and R , if present, are each independently selected from -H, -CN, -Hal, -OH, -NH2, C1-6 alkyl,C1-6haloalkyl, -O(C1-6alkyl), -O(C1-6haloalkyl), and -(C1-6alkylene)-O(C1-6alkyl). Preferably, RY1, RY2, RY3, and RY4are each independently selected from -H, -CN, -Hal, -OH, C1-6alkyl, C1-6haloalkyl, -O(C1-6alkyl), -O(C1-6haloalkyl), and -(C1-6alkylene)-O(C1-6alkyl). In a preferred embodiment, RY1, RY2, RY3, and RY4, if present, are each independently selectedfrom -H, -CN, -Hal, C1-6 alkyl, C1-6 haloalkyl, -O(C1-6 alkyl), and -O(C1-6 haloalkyl).In a more preferred embodiment, RY1, RY2, RY3, and RY4, if present, are each independently se- lected from -H, -Hal, C1alkyl, C1haloalkyl, -O(C1alkyl), and -O(C1haloalkyl). In an even more preferred embodiment, RY1, RY2, RY3, and RY4, if present, are each indepen- dently selected from -H, -Hal, C1alkyl, and C1Yhaloalkyl. In a particularly preferred embodiment, R 1, RY2, RY3, and RY4, if present, are each indepen-dently selected from -H, -Cl, -F, and -CH3. In one embodiment, the compound of formula (I) is a compound of formula (Ia), (Ib), or (Ic). Particularly preferably RY1and RY4, if present, are -H. Thus, in one embodiment, the compound of formula (I) is a compound of formula (Ia*), (Ib*),(Ic*), (Id*), (Ie*) or (If*) In a preferred embodiment, the compound of formula (I) is a compound of formula (Ia*), (Ib*),or (Ic*) In one preferred embodiment, the compound of formula (I) is a compound of formula (Ia*) In another preferred embodiment, the compound of formula (I) is a compound of formula (Ib*) In another preferred embodiment, the compound of formula (I) is a compound of formula (Ic*) In connection with the compounds of formula (Ia*), (Ib*), (Ic*), (Id*), (Ie*), and (If*), RY2and RY3, if present, are each independently selected from -H, -CN, -Hal, -OH, -NH2, C1-6alkyl, C1-6haloalkyl, -O(C1-6alkyl), -O(C1-6haloalkyl), and -(C1-6alkylene)-O(C1-6alkyl). Preferably, RY1, RY2,RY3, and RY4 are each independently selected from -H, -CN, -Hal, -OH, C1-6 alkyl, C1-6 haloalkyl,-O(C1-6alkyl), -O(C1-6haloalkyl), and -(C1-6alkylene)-O(C1-6alkyl). In a preferred embodiment, RY2and RY3, if present, are each independently selected from -H, - CN, -Hal, C1-6alkyl, C1-6haloalkyl, -O(C1-6alkyl), and -O(C1-6haloalkyl). In a more preferred embodiment, RY2and RY3, if present, are each independently selectedfrom -H, -Hal, C1 alkyl, C1 haloalkyl, -O(C1 alkyl), and -O(C1 haloalkyl).In an even more preferred embodiment, RY2and RY3, if present, are each independently se- lected from -H, -Hal, C1alkyl, and C1haloalkyl. In a particularly preferred embodiment, RY2and RY3, if present, are each independently se- lected from -H, -Cl, -F, and -CH3. In certain particularly preferred embodiments, RY2 and RY3, if present, are -H.In other particularly preferred embodiments, RY2, if present, is -H, and RY3, if present, is -Cl, -F, or -CH3. Compounds of formula (Ia*), wherein RY2and RY3are -H, will be referred to as compounds of formula (Ia*HH). Compounds of formula (Ia*), wherein RY2 is -H, and RY3 is -Cl, will be referred to as com-pounds of formula (Ia*HCl). Compounds of formula (Ia*), wherein RY2is -H, and RY3is -F, will be referred to as compounds of formula (Ia*HF). Compounds of formula (Ia*), wherein RY2is -H, and RY3is -CH3, will be referred to as com-pounds of formula (Ia*HCH3).Compounds of formula (Ib*), wherein RY2and RY3are -H, will be referred to as compounds of formula (Ib*HH). Compounds of formula (Ib*), wherein RY2is -H, and RY3is -Cl, will be referred to as com- pounds of formula (Ib*HCl). Compounds of formula (Ib*), wherein RY2is -H, and RY3is -F, will be referred to as compounds of formula (Ib*HF). Compounds of formula (Ib*), wherein RY2is -H, and RY3is -CH3, will be referred to as com- pounds of formula (Ib*HCH3). Compounds of formula (Ic*), wherein RY3 is -H, will be referred to as compounds of formula(Ic*H). Compounds of formula (Ic*), wherein RY3is -Cl, will be referred to as compounds of formula (Ic*Cl). Compounds of formula (Ic*), wherein RY3is -F, will be referred to as compounds of formula(Ic*F).Compounds of formula (Ic*), wherein RY3is - CH3, will be referred to as compounds of formula (Ic*CH3). In connection with the compounds of formula (I), as well as in connection with the compoundsof formula (Ia), (Ib), (Ic), (Id), (Ie) or (If) and in connection with the compounds of formula (Ia*),(Ib*), (Ic*), (Id*), (Ie*) or (If*), in particular in connection with the compounds of formula (Ia*), (Ib*), or (Ic*), especially in connection with the compounds of formula (Ia*HH), (Ia*HCl), (Ia*HF), (Ia*HCH3), (Ib*HH), (Ib*HCl), (Ib*HF), (Ib*HCH3), (Ic*H), (Ic*Cl), (Ic*F), (Ic*CH3), the following preferred embodiments regarding the substituents R1and A apply. In one embodiment, R1is phenyl substituted with one or more RS1; wherein each RS1is independently selected from -Hal, C1-6alkyl, C1-6haloalkyl, -cycloalkyl, -O(C1-6alkyl), -O(C1-6haloalkyl), and -NH-CO(C1-6alkyl); or two RS1together form a fused hete- rocycloalkyl or heteroaryl moiet In a preferred embodiment, R1y. is phenyl substituted with one RS1, wherein RS1 is selected from-Hal, C1-6alkyl, C1-6haloalkyl, -O(C1-6alkyl), and -O(C1-6haloalkyl). In a more preferred embodiment, R1is phenyl substituted with -O(C1-6alkyl). In an even more preferred embodiment, R1is phenyl substituted with ethoxy. In a still more preferred embodiment, R1is 4-ethoxyphenyl. In one embodiment, the moiety A is wherein the wavy line marks the connection to the remainder of the molecule; and wherR2ein: is C2-4 alkylene or C6 cycloalkylene, each optionally substituted with one or more RS2;wherein each RS2is independently selected from -OH, -F, and -CH3; or two RS2together form =O; each R3is independently selected from -H, C1-5alkyl, -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)- heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3S3 3alkylene)-heteroaryl, each optionally substitutedwith one or more R ; provided that not both R are -H;or the two R3together with the nitrogen atom to which they are attached form a heterocycloalkyl ring, optionally substituted with one or more RS3; wherein each RS3is independently selected from -CN, -Hal, -OH, -NH2, -NH(C1-6alkyl), -N(C1-6alkyl)(C1-6alkyl), C1-6alkyl, C1-6haloalkyl, -(C1-6alkylene)-CN, -(C1-6alkylene)-OH, -(C1-6alky-lene)- NH(C1-6 alkyl), -(C1-6 alkylene)- N(C1-6 alkyl)(C1-6 alkyl), -O(C1-6 alkyl), -O(C1-6 haloalkyl),-(C1-6alkylene)-O(C1-6alkyl), -S(C1-6alkyl), -S(C1-6haloalkyl), -(C1-6alkylene)-S(C1-6alkyl), -COH, -CO(C1-6alkyl), -CO(cycloalkyl), -CO(heterocycloalkyl), -COOH, -COO(C1-6alkyl), -CO-NH2, -CO-NH(C1-6alkyl), -CO-N(C1-6alkyl)(C1-6alkyl), -NH-CO(C1-6alkyl), -N(C1-6alkyl)-CO(C1-6alkyl), -S(O)2-(C1-6alkyl), -S(O)2-NH2, -S(O)2-NH(C1-6alkyl), -S(O)2-N(C1-6alkyl)(C1-6alkyl), -NH-S(O)2-(C1-6 alkyl), -N(C1-6 alkyl)-S(O)2-(C1-6 alkyl), -(C0-3 alkylene)-cycloalkyl, -(C0-3 alkylene)-heterocy-cloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-heteroaryl, wherein in said alkylene moiety of said -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-heteroaryl one -CH2- group if present is optionally replaced by -O-, and wherein the cycloalkyl moiety in said -(C0-3alkylene)-cycloalkyl, the heterocycloalkyl moiety in said -(C0-3 alkylene)-heterocycloalkyl, the aryl moiety in said -(C0-3alkylene)-aryl, and the heteroaryl moiety in said -(C0-3alkylene)-heteroaryl are each optionally substituted with one or more groups each independently selected from -Hal, C1-2alkyl, C1-2haloalkyl, -O(C1-2alkyl), and -O(C1-2haloalkyl); or two RS3attached to the same carbon atom form =O; or, if attached to a heterocycloalkyl by two R3 together with the nitrogen atom to which they are attached, two RSringformed 3 togetherwith two neighboring atoms to which they are attached form a fused heteroaryl ring. In connection with the above definitions, in particular the definitions of R3and RS3, cycloalkyl preferably refers to C3-7cycloalkyl, heterocycloalkyl preferably refers to 3- to 7-membered heterocycloalkyl, wherein the heterocy-cloalkyl ring comprises one or more ring heteroatoms independently selected from O, S and N,wherein the one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, aryl preferably refers to phenyl, and heteroaryl preferably refers to (5- or 6-membered heteroaryl), wherein the heteroaryl ring com-prises one or more ring heteroatoms independently selected from O, S and N, wherein the oneor more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized. Thus, -(C0-3alkylene)-cycloalkyl is preferably -(C0-3alkylene)-(C3-7cycloalkyl), -(C0-3alkylene)- heterocycloalkyl is preferably -(C0-3alkylene)-(3- to 7-membered heterocycloalkyl), -(C0-3alky-lene)-aryl is preferably -(C0-3 alkylene)-phenyl, and -(C0-3 alkylene)-heteroaryl is preferably -(C0-3alkylene)-(5- or 6-membered heteroaryl), wherein the heterocycloalkyl and heteroaryl rings inde- pendently comprise one or more ring heteroatoms independently selected from O, S and N, wherein the one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized. In connection with the substituents R3and RS3, it is preferred that the selection of these sub- stituents does not result in a heteroatom, e.g., an oxygen or nitrogen atom, or halogen atom di- rectly attached to a carbon atom, which is directly attached to the nitrogen atom contained in the A moiety. Thus, in a preferred embodiment, if RS3 is -Hal, -OH, -NH2, -NH(C1-6 alkyl), N(C1-6 alkyl)(C1-6alkyl) or a group, wherein -CH2- is replaced by O, it is preferred that the halogen, nitrogen, or oxygen atom of these RS3substituents is not directly attached to a carbon atom, which is di- rectly attached to the nitrogen atom contained in the A moiety. In another preferred embodiment, if two RS3attached to the same carbon atom form =O, it ispreferred that the =O is not attached to a carbon atom, which is directly attached to the nitrogenatom contained in the A moiety. In connection with the moiety A, the following preferred embodiments regarding R2and R3ap- ply. In a preferred embodiment, R2is C2alkylene or C3alkylene. In one particularly preferred embodiment, R2is C2alkylene. In another particularly preferred embodiment,R2is C3alkylene. In one preferred embodiment, each R3is independently selected from -H, C1-5alkyl, -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3 alkylene)-aryl, and -(C0-3 alkylene)-heteroaryl, each optionally substitutedwith one or more RS3; wherein each RS3is independently selected from -CN, -Hal, -OH, -NH2, -NH(C1-6alkyl), -N (C1-6alkyl)(C1-6alkyl), C1-6alkyl, C1-6haloalkyl, -(C1-6alkylene)-CN, -(C1-6alkylene)-OH, -O(C1-6alkyl), -(C1-6alkylene)-O-(C1-6alkyl), -CO(C1-6alkyl), -CO(cycloalkyl), -CO(heterocycloalkyl), -CO-NH2,-CO-NH(C1-6 alkyl), -CO-N(C1-6 alkyl)(C1-6 alkyl), -NH-CO(C1-6 alkyl), -S(O)2-(C1-6 alkyl), -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)- heteroaryl, wherein in said alkylene moiety of said -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)- heterocycloalkyl, -(C0-3alkylene)-aryl and -(C0-3alkylene)-heteroaryl one -CH2- group if present is optionally replaced by -O-, and wherein the cycloalkyl moiety in said -(C0-3alkylene)-cy- cloalkyl, the heterocycloalkyl moiety in said -(C0-3alkylene)-heterocycloalkyl, the aryl moiety insaid -(C0-3 alkylene)-aryl and the heteroaryl moiety in said -(C0-3 alkylene)-heteroaryl are eachoptionally substituted with one or more groups each independently selected from -Hal, C1-2alkyl, C1-2haloalkyl, and -O(C1-2alkyl); or two RS3attached to the same carbon atom form =O. In a m 3ore preferred embodiment,each R is independently selected from -H, C1-5 alkyl, -(C0-3 alkylene)-cycloalkyl, -(C0-3 alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-heteroaryl, each optionally substituted with one or more RS3; wherein each RS3is independently selected from -CN, -Hal, -OH, -NH2, C1-6alkyl, C1-6haloalkyl, and -O(C1-6alkyl).In an even more preferred embodiment,each R3is independently selected from -H, C1-5alkyl, -(C0-3alkylene)-(C3-7cycloalkyl), -(C0-3alkylene)-(3- to 7-membered heterocycloalkyl), -(C0-3alkylene)-phenyl, and -(C0-3alkylene)-(5- or 6-membered heteroaryl), each optionally substituted with one or more RS3, wherein the hete- rocycloalkyl and heteroaryl rings independently comprise one or more ring heteroatoms inde-pendently selected from O, S and N, wherein the one or more S ring atoms (if present) and / orone or more N ring atoms (if present) may optionally be oxidized; wherein each RS3is independently selected from -CN, -Hal, -OH, -NH2, C1-6alkyl, C1-6haloalkyl, and -O(C1-6alkyl). Particularly preferred moieties A in connection with the above definition of the two R3 are se-lected from the following groups: wherein the wavy line marks the connection to the remainder of the molecule;m is 0, 1, or 2; n is 0, 1, or 2; and wherein the above definitions for R2and RS3apply. I 2n particular, it is preferred in connection with the above moieties A thatR is C2 alkylene or C3 alkylene; andeach RS3is independently selected from -CN, -Hal, -OH, NH2, C1-6alkyl, C1-6haloalkyl, and -O(C1-6alkyl). Especially preferred moieties A in connection with the above definition of the two R3are se- lected from the following groups: wherein the wavy line marks the connection to the remainder of the molecule; and wherein the above definitions for R2apply. In particular, it is preferred in connection with the above moieties A thatR2is C2alkylene or C3alkylene. If R2is C2alkylene, the above moieties A are referred to as A-1-C2, A-2-C2, A-3-C2, and A-4- C2. If R2is C3alkylene, the above moieties A are referred to as A-1-C3, A-2-C3, A-3-C3, and A-4-C3.In another preferred embodiment, the two R3together with the nitrogen atom to which they are attached form a heterocycloalkyl ring, optionally substituted with oneS3S3or more R ;wherein each R is independently selected from -CN, -Hal, -OH, -NH2, -NH(C1-6 alkyl), -N(C1-6alkyl)(C1-6alkyl), C1-6alkyl, C1-6haloalkyl, -(C1-6alkylene)-CN, -(C1-6alkylene)-OH, -O(C1-6alkyl), -(C1-6alkylene)-O-(C1-6alkyl), -CO(C1-6alkyl), -CO(cycloalkyl), -CO(heterocycloalkyl), -CO-NH2, -CO-NH(C1-6alkyl), -CO-N(C1-6alkyl)(C1-6alkyl), -NH-CO(C1-6alkyl), -S(O)2-(C1-6alkyl), -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-heteroaryl, wherein in said alkylene moiety of said -(C0-3 alkylene)-cycloalkyl, -(C0-3 alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl and -(C0-3alkylene)-heteroaryl one -CH2- group if present is optionally replaced by -O-, and wherein the cycloalkyl moiety in said -(C0-3alkylene)-cy- cloalkyl, the heterocycloalkyl moiety in said -(C0-3alkylene)-heterocycloalkyl, the aryl moiety in said -(C0-3alkylene)-aryl and the heteroaryl moiety in said -(C0-3alkylene)-heteroaryl are eachoptionally substituted with one or more groups each independently selected from -Hal, C1-2 alkyl,C1-2haloalkyl, and -O(C1-2alkyl); or two RS3attached to the same carbon atom form =O; or two RS3together with two neighboring atoms to which they attached form a fused heteroaryl ring. In a mor 3e preferred embodiment,the two R together with the nitrogen atom to which they are attached form a heterocycloalkylring, optionally substituted with one or more RS3; the two R3together with the nitrogen atom to which they are attached form a heterocycloalkyl ring, optionally substituted with one or more RS3; wherein each RS3is independently selected from -CN, -Hal, -OH, -NH2, C1-6alkyl, C1-6haloalkyl,-O(C1-6 alkyl), -(C0-3 alkylene)-cycloalkyl, -(C0-3 alkylene)-heterocycloalkyl, -(C0-3 alkylene)-aryl,and -(C0-3alkylene)-heteroaryl, wherein in said alkylene moiety of said -(C0-3alkylene)-cy- cloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl and -(C0-3alkylene)-heteroaryl one -CH2- group if present is optionally replaced by -O-, and wherein the cycloalkyl moiety in said - (C0-3alkylene)-cycloalkyl, the heterocycloalkyl moiety in said -(C0-3alkylene)-heterocycloalkyl,the aryl moiety in said -(C0-3 alkylene)-aryl and the heteroaryl moiety in said -(C0-3 alkylene)-het-eroaryl are each optionally substituted with one or more groups each independently selected from -Hal, C1-2alkyl, C1-2haloalkyl, and -O(C1-2alkyl). In a more preferred embodiment, the two R3together with the nitrogen atom to which they are att Sa 3ched form a 3- to 7-memberedheterocycloalkyl ring, optionally substituted with one or more R , wherein the heterocycloalkylcomprises one or more ring heteroatoms independently selected from O, S and N, wherein the one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may option- ally be oxidized; wherein each RS3is independently selected from -CN, -Hal, -OH, -NH2, C1-6alkyl, C1-6haloalkyl, -O(C1-6alkyl), -(C0-3alkylene)-(C3-7cycloalkyl), -(C0-3alkylene)-(3- to 7-membered heterocy-cloalkyl), -(C0-3 alkylene)-phenyl, and -(C0-3 alkylene)-(5- or 6-membered heteroaryl), whereinthe heterocycloalkyl and heteroaryl rings independently comprise one or more ring heteroatoms independently selected from O, S and N, wherein the one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, and wherein in said alkylene moiety of said -(C0-3alkylene)-(C3-7cycloalkyl), -(C0-3alkylene)-(3- to 7-membered hete-rocycloalkyl), -(C0-3 alkylene)-phenyl and -(C0-3 alkylene)-(5- or 6-membered heteroaryl) one-CH2- group if present is optionally replaced by -O-, and wherein the cycloalkyl moiety in said - (C0-3alkylene)-(C3-7cycloalkyl), the heterocycloalkyl moiety in said -(C0-3alkylene)-(3- to 7-mem- bered heterocycloalkyl), the aryl moiety in said -(C0-3alkylene)-phenyl and the heteroaryl moiety in said -(C0-3alkylene)-(5- or 6-membered heteroaryl) are each optionally substituted with one ormore groups each independently selected from -Hal, C1-2 alkyl, C1-2 haloalkyl, and -O(C1-2 alkyl).Particularly preferred moieties A in connection with the above definition of the two R3are se- lected from the following groups: wherein the wavy line marks the connection to the remainder of the molecule; n is 0, 1, or 2; and wherein the above definitions for R2and RS3apply. I 2n particular, it is preferred in connection with the above moieties A thatR is C2 alkylene or C3 alkylene; andeach RS3is independently selected from -CN, -Hal, -OH, NH2, C1-6alkyl, C1-6haloalkyl, -O(C1-6alkyl), -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-heteroaryl, wherein in said alkylene moiety of said -(C0-3alkylene)-cycloalkyl, - (C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl and -(C0-3alkylene)-heteroaryl one -CH2-group if present is optionally replaced by -O-, and wherein the cycloalkyl moiety in said -(C0-3alkylene)-cycloalkyl, the heterocycloalkyl moiety in said -(C0-3alkylene)-heterocycloalkyl, the aryl moiety in said -(C0-3alkylene)-aryl and the heteroaryl moiety in said -(C0-3alkylene)-heteroaryl are each optionally substituted with one or more groups each independently selected from -Hal, C1-2alkyl, C1-2haloalkyl, and -O(C1-2alkyl). Especially preferred moieties A in connection with the above definition of R3 are selected fromthe following groups: wherein the wavy line marks the connection to the remainder of the molecule; and wherein the above definitions for R2apply. In particular, it is preferred in connection with the above moieties A that R2is C2alkylene or C3alkylene. If R2 is C2 alkylene, the above moieties A are referred to as A-5-C2, A-6-C2, A-7-C2, A-8-C2, A-9-C2, A-10-C2, A-11-C2, and A-12-C2. If R2is C3alkylene, the above moieties A are referred to as A-5-C3, A-6-C3, A-7-C3, A-8-C3, A- 9-C3, A-10-C3, A-11-C3, and A-12-C3. Overall, A is in a preferred embodiment a moiety selected from A-1-C2, A-2-C2, A-3-C2, A-4-C2,A-5-C2, A-6-C2, A-7-C2, A-8-C2, A-9-C2, A-10-C2, A-11-C2, A-12-C2, A-1-C3, A-2-C3, A-3-C3, A-4- C3, A-5-C3, A-6-C3, A-7-C3, A-8-C3, A-9-C3, A-10-C3, A-11-C3, and A-12-C3. In one particularly preferred embodiment, the moiety A is selected from A-1-C2, A-2-C2, A-3- C2, A-4-C2, A-5-C2, A-6-C2, A-7-C2, A-8-C2, A-9-C2, A-10-C2, A-11-C2, and A-12-C2. In another particularly preferred embodiment, the moiety A is selected from A-1-C3, A-2-C3, A-3-C3, A-4-C3, A-5-C3, A-6-C3, A-7-C3, A-8-C3, A-9-C3, A-10-C3, A-11-C3, and A-12-C3. Particularly preferred according to the invention are compounds of formula (Ia*HH), (Ia*HCl), (Ia*HF), (Ia*HCH3), (Ib*HH), (Ib*HCl), (Ib*HF), (Ib*HCH3), (Ic*H), (Ic*Cl), (Ic*F), (Ic*CH3),wherein R1 is 4-ethoxyphenyl and A is a moiety selected from A-1-C2, A-2-C2, A-3-C2, A-4-C2, A-5-C2, A-6-C2, A-7-C2, A-8-C2, A-9-C2, A-10-C2, A-11-C2, A-12-C2, A-1-C3, A-2-C3, A-3-C3, A-4- C3, A-5-C3, A-6-C3, A-7-C3, A-8-C3, A-9-C3, A-10-C3, A-11-C3, and A-12-C3. In one embodiment, the compound of formula (I) is a compound of formula (Ia*HH), wherein R1is 4-ethoxyphenyl and A is a moiety selected from A-1-C2, A-2-C2, A-3-C2, A-4-C2, A-5-C2, A-6-C2, A-7-C2, A-8-C2, A-9-C2, A-10-C2, A-11-C2, A-12-C2, A-1-C3, A-2-C3, A-3-C3, A-4-C3, A-5-C3, A-6-C3, A-7-C3, A-8-C3, A-9-C3, A-10-C3, A-11-C3, and A-12-C3. In another embodiment, the compound of formula (I) is a compound of formula (Ia*HCl), wherein R1is 4-ethoxyphenyl and A is a moiety selected from A-1-C2, A-2-C2, A-3-C2, A-4-C2, A- 5-C2, A-6-C2, A-7-C2, A-8-C2, A-9-C2, A-10-C2, A-11-C2, A-12-C2, A-1-C3, A-2-C3, A-3-C3, A-4-C3, A-5-C3, A-6-C3, A-7-C3, A-8-C3, A-9-C3, A-10-C3, A-11-C3, and A-12-C3.In another embodiment, the compound of formula (I) is a compound of formula (Ia*HF), wherein R1is 4-ethoxyphenyl and A is a moiety selected from A-1-C2, A-2-C2, A-3-C2, A-4-C2, A- 5-C2, A-6-C2, A-7-C2, A-8-C2, A-9-C2, A-10-C2, A-11-C2, A-12-C2, A-1-C3, A-2-C3, A-3-C3, A-4- C3, A-5-C3, A-6-C3, A-7-C3, A-8-C3, A-9-C3, A-10-C3, A-11-C3, and A-12-C3. In another embodiment, the compound of formula (I) is a compound of formula (Ia*HCH3),wherein R1is 4-ethoxyphenyl and A is a moiety selected from A-1-C2, A-2-C2, A-3-C2, A-4-C2, A- 5-C2, A-6-C2, A-7-C2, A-8-C2, A-9-C2, A-10-C2, A-11-C2, A-12-C2, A-1-C3, A-2-C3, A-3-C3, A-4- C3, A-5-C3, A-6-C3, A-7-C3, A-8-C3, A-9-C3, A-10-C3, A-11-C3, and A-12-C3. In one embodiment, the compound of formula (I) is a compound of formula (Ib*HH), whereinR1 is 4-ethoxyphenyl and A is a moiety selected from A-1-C2, A-2-C2, A-3-C2, A-4-C2, A-5-C2, A-6-C2, A-7-C2, A-8-C2, A-9-C2, A-10-C2, A-11-C2, A-12-C2, A-1-C3, A-2-C3, A-3-C3, A-4-C3, A-5-C3, A-6-C3, A-7-C3, A-8-C3, A-9-C3, A-10-C3, A-11-C3, and A-12-C3.In another embodiment, the compound of formula (I) is a compound of formula (Ib*HCl), wherein R1is 4-ethoxyphenyl and A is a moiety selected from A-1-C2, A-2-C2, A-3-C2, A-4-C2, A-5-C2, A-6-C2, A-7-C2, A-8-C2, A-9-C2, A-10-C2, A-11-C2, A-12-C2, A-1-C3, A-2-C3, A-3-C3, A-4-C3, A-5-C3, A-6-C3, A-7-C3, A-8-C3, A-9-C3, A-10-C3, A-11-C3, and A-12-C3. In another embodiment, the compound of formula (I) is a compound of formula (Ib*HF), wherein R1is 4-ethoxyphenyl and A is a moiety selected from A-1-C2, A-2-C2, A-3-C2, A-4-C2, A- 5-C2, A-6-C2, A-7-C2, A-8-C2, A-9-C2, A-10-C2, A-11-C2, A-12-C2, A-1-C3, A-2-C3, A-3-C3, A-4-C3, A-5-C3, A-6-C3, A-7-C3, A-8-C3, A-9-C3, A-10-C3, A-11-C3, and A-12-C3.In another embodiment, the compound of formula (I) is a compound of formula (Ib*HCH3), wherein R1is 4-ethoxyphenyl and A is a moiety selected from A-1-C2, A-2-C2, A-3-C2, A-4-C2, A- 5-C2, A-6-C2, A-7-C2, A-8-C2, A-9-C2, A-10-C2, A-11-C2, A-12-C2, A-1-C3, A-2-C3, A-3-C3, A-4- C3, A-5-C3, A-6-C3, A-7-C3, A-8-C3, A-9-C3, A-10-C3, A-11-C3, and A-12-C3. In one embodiment, the compound of formula (I) is a compound of formula (Ic*H), wherein R1is 4-ethoxyphenyl and A is a moiety selected from A-1-C2, A-2-C2, A-3-C2, A-4-C2, A-5-C2, A-6- C2, A-7-C2, A-8-C2, A-9-C2, A-10-C2, A-11-C2, A-12-C2, A-1-C3, A-2-C3, A-3-C3, A-4-C3, A-5-C3, A-6-C3, A-7-C3, A-8-C3, A-9-C3, A-10-C3, A-11-C3, and A-12-C3. In another embodiment, the compound of formula (I) is a compound of formula (Ic*Cl), wherein R1is 4-ethoxyphenyl and A is a moiety selected from A-1-C2, A-2-C2, A-3-C2, A-4-C2, A-5-C2, A-6-C2, A-7-C2, A-8-C2, A-9-C2, A-10-C2, A-11-C2, A-12-C2, A-1-C3, A-2-C3, A-3-C3, A-4-C3, A-5-C3, A-6-C3, A-7-C3, A-8-C3, A-9-C3, A-10-C3, A-11-C3, and A-12-C3. In another embodiment, the compound of formula (I) is a compound of formula (Ic*F), wherein R1is 4-ethoxyphenyl and A is a moiety selected from A-1-C2, A-2-C2, A-3-C2, A-4-C2, A-5-C2, A- 6-C2, A-7-C2, A-8-C2, A-9-C2, A-10-C2, A-11-C2, A-12-C2, A-1-C3, A-2-C3, A-3-C3, A-4-C3, A-5-C3, A-6-C3, A-7-C3, A-8-C3, A-9-C3, A-10-C3, A-11-C3, and A-12-C3.In another embodiment, the compound of formula (I) is a compound of formula (Ic*CH3), wherein R1is 4-ethoxyphenyl and A is a moiety selected from A-1-C2, A-2-C2, A-3-C2, A-4-C2, A- 5-C2, A-6-C2, A-7-C2, A-8-C2, A-9-C2, A-10-C2, A-11-C2, A-12-C2, A-1-C3, A-2-C3, A-3-C3, A-4- C3, A-5-C3, A-6-C3, A-7-C3, A-8-C3, A-9-C3, A-10-C3, A-11-C3, and A-12-C3. In yet another embodiment, the moiety A is , wherein the wavy line marks the connection to the remainder of the molecule; an 4d wherein:R is absent or C1-4 alkylene;R5is -H, -Hal, -OH, C1-6alkyl, or -O(C1-6alkyl); R6is C1-6alkyl, C1-6haloalkyl, -(C1-6alkylene)-OH, -(C1-6alkylene)-O(C1-6alkyl), -(C1-6alky- lene)-N(C1-6alkyl)(C1-6alkyl), -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, or -(C0-3alkylene)-heteroaryl, wherein in said alkylene moiety of said -(C0-3alky-lene)-cycloalkyl, -(C0-3 alkylene)-heterocycloalkyl, -(C0-3 alkylene)-aryl, and -(C0-3 alkylene)-het-eroaryl one -CH2- group if present is optionally replaced by -O-, and wherein the cycloalkyl moi- ety in said -(C0-3alkylene)-cycloalkyl, the heterocycloalkyl moiety in said -(C0-3alkylene)-hetero- cycloalkyl, the aryl moiety in said -(C0-3alkylene)-aryl and the heteroaryl moiety in said -(C0-3alkylene)-heteroaryl are each optionally substituted with one or more groups each indepen-dently selected from alkyl, C1-2 haloalkyl, and -O(C1-2 alkyl).In connection with the substituent R6, it is preferred that the selection of this substituent does not result in a heteroatom, e.g., an oxygen or nitrogen atom, or halogen atom directly attached to a carbon atom, which is directly attached to the nitrogen atom contained in the A moiety, andthat it does not result in a heteroatom, e.g., an oxygen atom, directly attached to the nitrogenatom contained in the A moiety. Thus, in a preferred embodiment, if R6is -(C1-6alkylene)-OH, -(C1-6alkylene)-O(C1-6alkyl), or - (C1-6alkylene)-N(C1-6alkyl)(C1-6alkyl), it is preferred that it is -(C2-6alkylene)-OH, -(C2-6alky- lene)-O(C1-6alkyl), or -(C2-6alkylene)-N(C1-6alkyl)(C1-6alkyl). Further, in a preferred embodiment, if R6 represents a group, wherein -CH2- is replaced by -O-,it is preferred that the oxygen atom is not directly attached to the carbon atom, which is directly attached to the nitrogen atom contained in the A moiety, and that it is not directly attached to the nitrogen atom contained in the A moiety. In yet another embodiment, the moiety A is , wherein the wavy line marks the connection to the remainder of the molecule; and wherein: R4is absent or C1-4alkylene;R5 is -Hal, -OH, alkyl, or -O(C1-6 alkyl); R6is C1-6alkyl, C1-6haloalkyl, -(C1-6alkylene)-OH, -(C1-6alkylene)-O(C1-6alkyl), -(C1-6alky- lene)-N(C1-6alkyl)(C1-6alkyl), -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, or -(C0-3alkylene)-heteroaryl, wherein in said alkylene moiety of said -(C0-3alky- lene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-het-eroaryl one -CH2- group if present is optionally replaced by -O-, and wherein the cycloalkyl moi-ety in said -(C0-3alkylene)-cycloalkyl, the heterocycloalkyl moiety in said -(C0-3alkylene)-hetero- cycloalkyl, the aryl moiety in said -(C0-3alkylene)-aryl and the heteroaryl moiety in said -(C0-3alkylene)-heteroaryl are each optionally substituted with one or more groups each indepen- dently selected from -Hal, C1-2alkyl, C1-2haloalkyl, and -O(C1-2alkyl). In a preferred embodiment,R6is C1-6alkyl, C1-6haloalkyl, -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, or -(C0-3alkylene)-heteroaryl, wherein in said alkylene moiety of said -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)- heteroaryl one -CH2- group if present is optionally replaced by -O-, and wherein the cycloalkylmoiety in said -(C0-3 alkylene)-cycloalkyl, the heterocycloalkyl moiety in said -(C0-3 alkylene)-het-erocycloalkyl, the aryl moiety in said -(C0-3alkylene)-aryl and the heteroaryl moiety in said -(C0-3alkylene)-heteroaryl are each optionally substituted with one or more groups each indepen- dently selected from -Hal, C1-2alkyl, C1-2haloalkyl, and -O(C1-2alkyl). I 6n a more preferred embodiment,R is C1-6 alkyl, C1-6 haloalkyl, -(C0-3 alkylene)-(C3-7 cycloalkyl), -(C0-3 alkylene)-(3- to 7-mem-bered heterocycloalkyl), -(C0-3alkylene)-phenyl, or -(C0-3alkylene)-(5- or 6-membered het- eroaryl), wherein the heterocycloalkyl and heteroaryl rings independently comprise one or more ring heteroatoms independently selected from O, S and N, wherein the one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, andwherein in said alkylene moiety of said -(C0-3 alkylene)-(C3-7 cycloalkyl), -(C0-3 alkylene)-(3- to 7-membered heterocycloalkyl), -(C0-3alkylene)-phenyl and -(C0-3alkylene)-(5- or 6-membered het- eroaryl) one -CH2- group if present is optionally replaced by -O-, and wherein the cycloalkyl moi- ety in said -(C0-3alkylene)-(C3-7cycloalkyl), the heterocycloalkyl moiety in said -(C0-3alkylene)- (3- to 7-membered heterocycloalkyl), the aryl moiety in said -(C0-3alkylene)-phenyl and the het-eroaryl moiety in said -(C0-3 alkylene)-(5- or 6-membered heteroaryl) are each optionally substi-tuted with one or more groups each independently selected from alkyl, C1-2haloalkyl, and -O(C1-2alkyl). In another preferred embodiment, the moiety A is ; wherein the wavy line marks the connection to the remainder of the molecule; and wherein: R6is C1-6alkyl, C1-6haloalkyl, -(C1-6alkylene)-OH, -(C1-6alkylene)-O(C1-6alkyl), -(C1-6alky- lene)-N(C1-6alkyl)(C1-6alkyl), -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, or -(C0-3 alkylene)-heteroaryl, wherein in said alkylene moiety of said -(C0-3 alky-lene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-het- eroaryl one -CH2- group if present is optionally replaced by -O-, and wherein the cycloalkyl moi- ety in said -(C0-3alkylene)-cycloalkyl, the heterocycloalkyl moiety in said -(C0-3alkylene)-hetero- cycloalkyl, the aryl moiety in said -(C0-3alkylene)-aryl and the heteroaryl moiety in said -(C0-3alkylene)-heteroaryl are each optionally substituted with one or more groups each indepen-dently selected from alkyl, C1-2haloalkyl, and -O(C1-2alkyl). Preferably, R6is C1-6alkyl, C1-6haloalkyl, -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, or -(C0-3alkylene)-heteroaryl, wherein in said alkylene moiety of said -(C0-3alkylene)-cycloalkyl, -(C0-3 alkylene)-heterocycloalkyl, -(C0-3 alkylene)-aryl, and -(C0-3 alkylene)-heteroaryl one -CH2- group if present is optionally replaced by -O-, and wherein the cycloalkyl moiety in said -(C0-3alkylene)-cycloalkyl, the heterocycloalkyl moiety in said -(C0-3alkylene)-het- erocycloalkyl, the aryl moiety in said -(C0-3alkylene)-aryl and the heteroaryl moiety in said -(C0-3 alkylene)-heteroaryl are each optionally substituted with one or more groups each indepen- dently selected from -Hal, C1-2alkyl, C1-2haloalkyl, and -O(C1-2alkyl). More preferably, R6is C1-6alkyl, C1-6haloalkyl, -(C0-3alkylene)-(C3-7cycloalkyl), -(C0-3alkylene)-(3- to 7-mem-bered heterocycloalkyl), -(C0-3 alkylene)-phenyl, or -(C0-3 alkylene)-(5- or 6-membered het-eroaryl), wherein the heterocycloalkyl and heteroaryl rings independently comprise one or more ring heteroatoms independently selected from O, S and N, wherein the one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, and wherein in said alkylene moiety of said -(C0-3alkylene)-(C3-7cycloalkyl), -(C0-3alkylene)-(3- to 7-membered heterocycloalkyl), -(C0-3 alkylene)-phenyl and -(C0-3 alkylene)-(5- or 6-membered het-eroaryl) one -CH2- group if present is optionally replaced by -O-, and wherein the cycloalkyl moi- ety in said -(C0-3alkylene)-(C3-7cycloalkyl), the heterocycloalkyl moiety in said -(C0-3alkylene)- (3- to 7-membered heterocycloalkyl), the aryl moiety in said -(C0-3alkylene)-phenyl and the het- eroaryl moiety in said -(C0-3alkylene)-(5- or 6-membered heteroaryl) are each optionally substi-tuted with one or more groups each independently selected from -Hal, C1-2 alkyl, C1-2 haloalkyl,and -O(C1-2alkyl). Particularly preferred compounds of formula (I) are selected from the following compounds or a stereoisomer, tautomer, N-oxide, pharmaceutically acceptable salt or solvate thereof: Further preferred compounds of formula (I) are selected from the following compounds or a stereoisomer, tautomer, N-oxide, pharmaceutically acceptable salt or solvate thereof:

[0064] Further preferred compounds of formula (I) are selected from the following compounds or a stereoisomer, tautomer, N-oxide, pharmaceutically acceptable salt or solvate thereof:

[0065]

[0066] The scope of the invention embraces all pharmaceutically acceptable salt forms of the com- pounds of formula (I) which may be formed, e.g., by protonation of an atom carrying an electron lone pair which is susceptible to protonation, such as an amino group, with an inorganic or or- ganic acid, or as a salt of an acid group (such as a carboxylic acid group) with a physiologically acceptable cation. Exemplary base addition salts comprise, for example: alkali metal salts such as sodium or potassium salts; alkaline earth metal salts such as calcium or magnesium salts; zinc salts; ammonium salts; aliphatic amine salts such as trimethylamine, triethylamine, dicyclo- hexylamine, ethanolamine, diethanolamine, triethanolamine, procaine salts, meglumine salts, ethylenediamine salts, or choline salts; aralkyl amine salts such as N,N-dibenzylethylenedi- amine salts, benzathine salts, benethamine salts; heterocyclic aromatic amine salts such as pyridine salts, picoline salts, quinoline salts or isoquinoline salts; quaternary ammonium salts such as tetramethylammonium salts, tetraethylammonium salts, benzyltrimethylammonium salts, benzyltriethylammonium salts, benzyltributylammonium salts, methyltrioctylammonium salts or tetrabutylammonium salts; and basic amino acid salts such as arginine salts, lysine salts, or histidine salts. Exemplary acid addition salts comprise, for example: mineral acid salts such as hydrochloride, hydrobromide, hydroiodide, sulfate salts (such as, e.g., sulfate or hydro- gensulfate salts), nitrate salts, phosphate salts (such as, e.g., phosphate, hydrogenphosphate, or dihydrogenphosphate salts), carbonate salts, hydrogencarbonate salts, perchlorate salts, bo- rate salts, or thiocyanate salts; organic acid salts such as acetate, propionate, butyrate, pen- tanoate, hexanoate, heptanoate, octanoate, cyclopentanepropionate, decanoate, undecanoate, oleate, stearate, lactate, maleate, oxalate, fumarate, tartrate, malate, citrate, succinate, adipate, gluconate, glycolate, nicotinate, benzoate, salicylate, ascorbate, pamoate (embonate), cam- phorate, glucoheptanoate, or pivalate salts; sulfonate salts such as methanesulfonate (mesy- late), ethanesulfonate (esylate), 2-hydroxyethanesulfonate (isethionate), benzenesulfonate (be- sylate), p-toluenesulfonate (tosylate), 2-naphthalenesulfonate (napsylate), 3-phenylsulfonate, or camphorsulfonate salts; glycerophosphate salts; and acidic amino acid salts such as aspartate or glutamate salts. Preferred pharmaceutically acceptable salts of the compounds of formula (I) include a hydrochloride salt, a hydrobromide salt, a mesylate salt, a sulfate salt, a tartrate salt, a fumarate salt, an acetate salt, a citrate salt, and a phosphate salt. A particularly preferred phar- maceutically acceptable salt of the compound of formula (I) is a hydrochloride salt. Accordingly, it is preferred that the compound of formula (I), including any one of the specific compounds of formula (I) described herein, is in the form of a hydrochloride salt, a hydrobromide salt, a mesy- late salt, a sulfate salt, a tartrate salt, a fumarate salt, an acetate salt, a citrate salt, or a phos- phate salt, and it is particularly preferred that the compound of formula (I) is in the form of a hy- drochloride salt.

[0067] The present invention also specifically relates to the compound of formula (I), including any one of the specific compounds of formula (I) described herein, in non-salt form.

[0068] Moreover, the scope of the invention embraces the compounds of formula (I) in any solvated form, including, e.g., solvates with water (i.e. , as a hydrate) or solvates with organic solvents such as, e.g., methanol, ethanol, isopropanol, acetic acid, ethyl acetate, ethanolamine, DMSO, or acetonitrile. All physical forms, including any amorphous or crystalline forms (i.e., poly- morphs), of the compounds of formula (I) are also encompassed within the scope of the inven- tion. It is to be understood that such solvates and physical forms of pharmaceutically acceptable salts of the compounds of the formula (I) are likewise embraced by the invention.

[0069] Furthermore, the compounds of formula (I) may exist in the form of different isomers, in partic- ular stereoisomers (including, e.g., geometric isomers (or cis / trans isomers), enantiomers and diastereomers) or tautomers (including, in particular, prototropic tautomers, such as keto / enol tautomers or thione / thiol tautomers). All such isomers of the compounds of formula (I) are con- templated as being part of the present invention, either in admixture or in pure or substantially pure form. As for stereoisomers, the invention embraces the isolated optical isomers of the compounds according to the invention as well as any mixtures thereof (including, in particular, racemic mixtures / racemates). The racemates can be resolved (i.e., separated) by physical methods, such as, e.g., fractional crystallization, separation or crystallization of diastereomeric derivatives, or separation by chiral column chromatography. The individual optical isomers can also be obtained from the racemates via salt formation with an optically active acid followed by crystallization. The present invention further encompasses any tautomers of the compounds of formula (I). It will be understood that some compounds may exhibit tautomerism. In such cases, the formulae provided herein expressly depict only one of the possible tautomeric forms. The formulae and chemical names as provided herein are intended to encompass any tautomeric form of the corresponding compound and not to be limited merely to the specific tautomeric form depicted by the drawing or identified by the name of the compound.

[0070] Furthermore, the compounds of formula (I) may exist in the form of N-oxides, i.e. in a form with at least one tertiary nitrogen atom being oxidized to an N-oxide moiety.

[0071] The scope of the invention also embraces compounds of formula (I), in which one or more atoms are replaced by a specific isotope of the corresponding atom. For example, the invention encompasses compounds of formula (I), in which one or more hydrogen atoms (or, e.g., all hy- drogen atoms) are replaced by deuterium atoms (i.e.,2H; also referred to as “D”). Accordingly, the invention also embraces compounds of formula (I) which are enriched in deuterium. Natu- rally occurring hydrogen is an isotopic mixture comprising about 99.98 mol-% hydrogen-1 (1H) and about 0.0156 mol-% deuterium (2H or D). The content of deuterium in one or more hydro- gen positions in the compounds of formula (I) can be increased using deuteration techniques known in the art. For example, a compound of formula (I) or a reactant or precursor to be used in the synthesis of the compound of formula (I) can be subjected to an H / D exchange reaction using, e.g., heavy water (D2O). Further suitable deuteration techniques are described in: Atzrodt J et al., Bioorg Med Chem, 20(18), 5658-5667, 2012; William JS et al., Journal of Labelled Compounds and Radiopharmaceuticals, 53(11-12), 635-644, 2010; Modvig A et al., J Org Chem, 79, 5861-5868, 2014. The content of deuterium can be determined, e.g., using mass spectrometry or NMR spectroscopy. Unless specifically indicated otherwise, it is preferred that the compound of formula (I) is not enriched in deuterium. Accordingly, the presence of naturally occurring hydrogen atoms or1H hydrogen atoms in the compounds of formula (I) is preferred.

[0072] The present invention also embraces compounds of formula (I), in which one or more atoms are replaced by a positron-emitting isotope of the corresponding atom, such as, e.g.,18F,11C,13N,150,76Br,77Br,120l and / or124l. Such compounds can be used as tracers, trackers or imaging probes in positron emission tomography (PET). The invention thus includes (i) compounds of formula (I), in which one or more fluorine atoms (or, e.g., all fluorine atoms) are replaced by18F atoms, (ii) compounds of formula (I), in which one or more carbon atoms (or, e.g., all carbon atoms) are replaced by11C atoms, (iii) compounds of formula (I), in which one or more nitrogen atoms (or, e.g., all nitrogen atoms) are replaced by13N atoms, (iv) compounds of formula (I), in which one or more oxygen atoms (or, e.g., all oxygen atoms) are replaced by15O atoms, (v) compounds of formula (I), in which one or more bromine atoms (or, e.g., all bromine atoms) are replaced by76Br atoms, (vi) compounds of formula (I), in which one or more bromine atoms (or, e.g., all bromine atoms) are replaced by77Br atoms, (vii) compounds of formula (I), in which one or more iodine atoms (or, e.g., all iodine atoms) are replaced by120l atoms, and (viii) com- pounds of formula (I), in which one or more iodine atoms (or, e.g., all iodine atoms) are replaced by124l atoms. In general, it is preferred that none of the atoms in the compounds of formula (I) are replaced by specific isotopes.

[0073] The compounds provided herein may be administered as compounds perse or may be formu- lated as medicaments. The medicaments / pharmaceutical compositions may optionally comprise one or more pharmaceutically acceptable excipients, such as carriers, diluents, fillers, disinte- grants, lubricating agents, binders, colorants, pigments, stabilizers, preservatives, antioxidants, and / or solubility enhancers.

[0074] The pharmaceutical compositions may comprise one or more solubility enhancers, such as, e.g., poly(ethylene glycol), including poly(ethylene glycol) having a molecular weight in the range of about 200 to about 5,000 Da (e.g., PEG 200, PEG 300, PEG 400, or PEG 600), ethyl- ene glycol, propylene glycol, glycerol, a non-ionic surfactant, tyloxapol, polysorbate 80, macro- gol-15-hydroxystearate (e.g., Kolliphor® HS 15, CAS 70142-34-6), a phospholipid, lecithin, dimyristoyl phosphatidylcholine, dipalmitoyl phosphatidylcholine, distearoyl phosphatidylcholine, a cyclodextrin, a-cyclodextrin, p-cyclodextrin, y-cyclodextrin, hydroxyethyl-p-cyclodextrin, hy- droxypropyl-p-cyclodextrin, hydroxyethyl-y-cyclodextrin, hydroxypropyl-y-cyclodextrin, dihydrox- ypropyl-p-cyclodextrin, sulfobutylether-p-cyclodextrin, sulfobutylether-y-cyclodextrin, glucosyl-a- cyclodextrin, glucosyl-p-cyclodextrin, diglucosyl-p-cyclodextrin, maltosyl-a-cyclodextrin, malto- syl-p-cyclodextrin, maltosyl-y-cyclodextrin, maltotriosyl-p-cyclodextrin, maltotriosyl-y-cyclodex- trin, dimaltosyl-p-cyclodextrin, methyl-p-cyclodextrin, a carboxyalkyl thioether, hydroxypropyl methylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, a vinyl acetate copolymer, vinyl pyrrolidone, sodium lauryl sulfate, dioctyl sodium sulfosuccinate, or any combination thereof.

[0075] The pharmaceutical compositions may also comprise one or more preservatives, particularly one or more antimicrobial preservatives, such as, e.g., benzyl alcohol, chlorobutanol, 2-ethoxyethanol, m-cresol, chlorocresol (e.g., 2-chloro-3-methyl-phenol or 4-chloro-3-methyl- phenol), benzalkonium chloride, benzethonium chloride, benzoic acid (or a pharmaceutically ac- ceptable salt thereof), sorbic acid (or a pharmaceutically acceptable salt thereof), chlorhexidine, thimerosal, or any combination thereof. The pharmaceutical compositions can be formulated by techniques known to the person skilled in the art, such as the techniques published in “Remington: The Science and Practice of Pharmacy”, Pharmaceutical Press, 22ndedition. The pharmaceutical compositions can be for- mulated as dosage forms for oral, parenteral, such as intramuscular, intravenous, subcuta- neous, intradermal, intraarterial, intracardial, rectal, nasal, topical, aerosol or vaginal administra- tion. Dosage forms for oral administration include coated and uncoated tablets, soft gelatin cap- sules, hard gelatin capsules, lozenges, troches, solutions, emulsions, suspensions, syrups, elixirs, powders and granules for reconstitution, dispersible powders and granules, medicated gums, chewing tablets and effervescent tablets. Dosage forms for parenteral administration in- clude solutions, emulsions, suspensions, dispersions and powders and granules for reconstitu- tion. Emulsions are a preferred dosage form for parenteral administration. Dosage forms for rec- tal and vaginal administration include suppositories and ovula. Dosage forms for nasal adminis- tration can be administered via inhalation and insufflation, for example by a metered inhaler. Dosage forms for topical administration include creams, gels, ointments, salves, patches and transdermal delivery systems.

[0076] The compounds of formula (I) or the above described pharmaceutical compositions comprising a compound of formula (I) may be administered to a subject by any convenient route of adminis- tration, whether systemically / peripherally or at the site of desired action, including but not limited to one or more of: oral (e.g., as a tablet, capsule, or as an ingestible solution), topical (e.g., transdermal, intranasal, ocular, buccal, and sublingual), parenteral (e.g., using injection tech- niques or infusion techniques, and including, for example, by injection, e.g., subcutaneous, in- tradermal, intramuscular, intravenous, intraarterial, intracardiac, intrathecal, intraspinal, intra- capsular, subcapsular, intraorbital, intraperitoneal, intratracheal, subcuticular, intraarticular, sub- arachnoid, or intrasternal by, e.g., implant of a depot, for example, subcutaneously or intramus- cularly), pulmonary (e.g., by inhalation or insufflation therapy using, e.g., an aerosol, e.g., through mouth or nose), gastrointestinal, intrauterine, intraocular, subcutaneous, ophthalmic (in- cluding intravitreal or intracameral), rectal, or vaginal administration.

[0077] If said compounds or pharmaceutical compositions are administered parenterally, then exam- ples of such administration include one or more of: intravenously, intraarterially, intraperi- toneally, intrathecally, intraventricularly, intraurethrally, intrasternally, intracardially, intracra- nially, intramuscularly or subcutaneously administering the compounds or pharmaceutical com- positions, and / or by using infusion techniques. For parenteral administration, the compounds are best used in the form of a sterile aqueous solution which may contain other substances, for example, enough salts or glucose to make the solution isotonic with blood. The aqueous solu- tions should be suitably buffered (preferably to a pH of from 3 to 9), if necessary. The prepara- tion of suitable parenteral formulations under sterile conditions is readily accomplished by stan- dard pharmaceutical techniques well known to those skilled in the art.

[0078] Said compounds or pharmaceutical compositions can also be administered orally in the form of tablets, capsules, ovules, elixirs, solutions or suspensions, which may contain flavoring or coloring agents, for immediate-, delayed-, modified-, sustained-, pulsed- or controlled-release applications.

[0079] The tablets may contain excipients such as microcrystalline cellulose, lactose, sodium citrate, calcium carbonate, dibasic calcium phosphate and glycine, disintegrants such as starch (prefer- ably corn, potato or tapioca starch), sodium starch glycolate, croscarmellose sodium and certain complex silicates, and granulation binders such as polyvinylpyrrolidone, hydroxypropylmethyl- cellulose (HPMC), hydroxypropylcellulose (HPC), sucrose, gelatin and acacia. Additionally, lu- bricating agents such as magnesium stearate, stearic acid, glyceryl behenate and talc may be included. Solid compositions of a similar type may also be employed as fillers in gelatin cap- sules. Preferred excipients in this regard include lactose, starch, a cellulose, or high molecular weight polyethylene glycols. For aqueous suspensions and / or elixirs, the agent may be com- bined with various sweetening or flavoring agents, coloring matter or dyes, with emulsifying and / or suspending agents and with diluents such as water, ethanol, propylene glycol and glyc- erin, and combinations thereof.

[0080] For oral administration, the compounds or pharmaceutical compositions are preferably admin- istered by oral ingestion, particularly by swallowing. The compounds or pharmaceutical compo- sitions can thus be administered to pass through the mouth into the gastrointestinal tract, which can also be referred to as “oral-gastrointestinal” administration.

[0081] Alternatively, said compounds or pharmaceutical compositions can be administered in the form of a suppository or pessary, or may be applied topically in the form of a gel, hydrogel, lo- tion, solution, cream, ointment or dusting powder. The compounds of the present invention may also be dermally or transdermally administered, for example, by the use of a skin patch.

[0082] Said compounds or pharmaceutical compositions may also be administered by sustained re- lease systems. Suitable examples of sustained-release compositions include semi-permeable polymer matrices in the form of shaped articles, e.g., films, or microcapsules. Sustained-release matrices include, e.g., polylactides, copolymers of L-glutamic acid and gamma-ethyl-L-gluta- mate, poly(2-hydroxyethyl methacrylate), ethylene vinyl acetate, or poly-D-(-)-3-hydroxybutyric acid. Sustained-release pharmaceutical compositions also include liposomally entrapped com- pounds. The present invention thus also relates to liposomes containing a compound of the in- vention.

[0083] Said compounds or pharmaceutical compositions may also be administered by the pulmonary route, rectal routes, or the ocular route. For ophthalmic use, they can be formulated as mi- cronized suspensions in isotonic, pH adjusted, sterile saline, or, preferably, as solutions in iso- tonic, pH adjusted, sterile saline, optionally in combination with a preservative such as a benza- lkonium chloride. Alternatively, they may be formulated in an ointment such as petrolatum.

[0084] It is also envisaged to prepare dry powder formulations of the compounds of formula (I) for pul- monary administration, particularly inhalation. Such dry powders may be prepared by spray dry- ing under conditions which result in a substantially amorphous glassy or a substantially crys- talline bioactive powder. Accordingly, dry powders of the compounds of the present invention can be made according to an emulsification / spray drying process.

[0085] For topical application to the skin, said compounds or pharmaceutical compositions can be for- mulated as a suitable ointment containing the active compound suspended or dissolved in, for example, a mixture with one or more of the following: mineral oil, liquid petrolatum, white petro- latum, propylene glycol, emulsifying wax and water. Alternatively, they can be formulated as a suitable lotion or cream, suspended or dissolved in, for example, a mixture of one or more of the following: mineral oil, sorbitan monostearate, a polyethylene glycol, liquid paraffin, polysorbate 60, cetyl esters wax, 2-octyldodecanol, benzyl alcohol and water.

[0086] The present invention thus relates to the compounds or the pharmaceutical compositions pro- vided herein, wherein the corresponding compound or pharmaceutical composition is to be ad- ministered by any one of: an oral route; topical route, including by transdermal, intranasal, ocu- lar, buccal, or sublingual route; parenteral route using injection techniques or infusion tech- niques, including by subcutaneous, intradermal, intramuscular, intravenous, intraarterial, intrac- ardiac, intrathecal, intraspinal, intracapsular, subcapsular, intraorbital, intraperitoneal, intratra- cheal, subcuticular, intraarticular, subarachnoid, intrasternal, intraventricular, intraurethral, or in- tracranial route; pulmonary route, including by inhalation or insufflation therapy; gastrointestinal route; intrauterine route; intraocular route; subcutaneous route; ophthalmic route, including by intravitreal, or intracameral route; rectal route; or vaginal route. Preferred routes of administra- tion are oral administration or parenteral administration. For each of the compounds or pharma- ceutical compositions provided herein, it is particularly preferred that the respective compound or pharmaceutical composition is to be administered orally (particularly by oral ingestion).

[0087] Typically, a physician will determine the actual dosage which will be most suitable for an indi- vidual subject. The specific dose level and frequency of dosage for any particular individual sub- ject may be varied and will depend upon a variety of factors including the activity of the specific compound employed, the metabolic stability and length of action of that compound, the age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular condition, and the individual subject undergoing ther- apy.

[0088] A proposed, yet non-limiting dose of the compounds according to the invention for oral admin- istration to a human (of approximately 70 kg body weight) may be 0.05 to 2000 mg, preferably 0.1 mg to 1000 mg, of the active ingredient per unit dose. The unit dose may be administered, e.g., 1 to 3 times per day. The unit dose may also be administered 1 to 7 times per week, e.g., with not more than one administration per day. It will be appreciated that it may be necessary to make routine variations to the dosage depending on the age and weight of the patient / subject as well as the severity of the condition to be treated. The precise dose and also the route of ad- ministration will ultimately be at the discretion of the attendant physician or veterinarian.

[0089] The therapeutic use of the compounds of the present invention will be described in the follow- ing.

[0090] In one embodiment, the present invention relates to the compound of formula (I) or a pharma- ceutically acceptable salt thereof for use as a medicament.

[0091] Without wishing to be bound by theory, the present inventors have demonstrated that, as TASL level is regulated by its interaction with SLC15A4, the treatment with the compounds of formula (I) leads to efficient degradation of TASL.

[0092] It is known to the skilled person and apparent from the literature that SLC15A4 and / or TASL play a crucial role in autoimmune disorders (including SLE) and inflammatory disorders (includ- ing inflammatory bowel disease (IBD), psoriasis, and endosomal TLR-dependent inflammation).

[0093] Accordingly, there is a body of evidence based on genome wide association studies (GWAS) of SLE in human cells indicating the role SLC15A4 in this disorder. Bentham et al. (Bentham et al, (2015)) identified the genetic association of SLC15A4 and TASL (referenced therein as CX- orf21) with SLE in a cohort of European ancestry. He CF and coworkers (He et al, (2010)) iden- tified the genetic association of SLC15A4 with SLE-related discoid rash in a Chinese Han pop- ulation. Langefeld and coworkers (Langefeld et al. Transancestral mapping and genetic load in systemic lupus erythematosus. Nat Commun, 8, 16021 (2017)) identified the genetic association of SLC15A4 with SLE in a cohort of European ancestry.

[0094] Further, there is additional evidence of the role of TASL in the pathogenesis of SLE based on genetic studies in human cells. Odhams et al. (Odhams et al (2019)) proposed that genetic vari- ants of TASL (CXorf21) associated with SLE lead to increased TASL expression in an inter- feron- and sex-specific manner and hence suggest a potential explanation.

[0095] There is further evidence in mouse models indicating the importance of TASL / SLC15A4 in the development of SLE. Baccala and coworkers (Baccala et al. Essential requirement for IRF8 and SLC15A4 implicates pDCs in the pathogenesis of lupus. PNAS, 110, 2940, (2013)) identified a protective role for SLC15A4 deficiency in the development of SLE in a mouse model using the C57BL / 6-Fas(lpr) strain. Kobayashi and coworkers (Kobayashi et al. (2014)) show that SLC15A4-deficiency is protective in two models of SLE (pristane-induced and C57BL / 6lpr / lpr mice) and that SLC15A4 is required in B cells for endosomal TLR function. Pollard and cowork- ers (Pollard et al. Induction of Systemic Autoimmunity by a Xenobiotic Requires Endosomal TLR Trafficking and Signaling from the Late Endosome and Endolysosome but Not Type I IFN. J Immunol, 199, 3739, (2017)) found that SLC15A4-deficiency is protective in a mercury-in- duced model of SLE. Katewa and coworkers (Katewa et al. (2021)) describe a protective role for SLC15A4 in pristane-induced and NZB / W F1 murine genetic models of SLE.

[0096] Accordingly, the compounds of the present invention are considered useful in the treatment or prevention of autoimmune disorders, in particular SLE.

[0097] It can be further assumed based on the role of SLC15A4 and / or TASL in IRF5 activation, that the compounds of the present invention will be useful in the treatment or prevention of autoim- mune disorders, preferably selected from SLE, lupus nephritis, rheumatoid arthritis, sclero- derma, Sjogren’s syndrome, polymyositis / dermatomyositis, primary biliary cirrhosis, multiple sclerosis, oral ulcers, periodontitis, Behget’s disease, inflammatory bowel disease, psoriasis, myasthenia gravis, and ankylosing spondylitis (Wang et al. (2023), Bentham et al. 2015), Katewa et al. (2021)).

[0098] There is further a body of evidence based on genetic studies indicating the role of SLC15A4 and / or TASL in proinflammatory cytokine production (such as IL-6) and inflammation. Heinz and coworkers (Heinz et al. (2020)) have shown an essential role of SLC15A4-TASL and their rela- tionship in human cell lines and primary cells for endosomal TLR function.

[0099] There is further evidence based on studies in mouse models indicating the role of SLC15A4 and / or TASL in inflammatory conditions. Blasius and coworkers (Blasius et al. (2010)) identified SLC15A4 as essential component in endosomal TLR function in pDCs. Sasawatari and cowork- ers (Sasawatari et al. The solute carrier family 15A4 regulates TLR9 and NOD1 functions in the innate immune system and promotes colitis in mice. Gastroenterology, 140, 1513, (2011)) have found SLC15A4-deficiency to impair CpG-induced production of proinflammatory cytokines from dendritic cells. Furthermore, SLC15A4-deficiency was found to be protective in a mouse model of IBD. SLC15A4-deficient mice also showed defective cytokine production upon activation of the NOD-like receptor NOD1. Blasius and coworkers (Blasius et al. Slc15a4, a gene required for pDC sensing of TLR ligands, is required to control persistent viral infection. PLoS Pathog 8, e1002915 (2012)) suggested an important role for SLC15A4 in pDCs in controlling viral persist- ence, as evidenced in a model of LCMV infection. Nakamura and coworkers (Nakamura et al. Endosomes are specialized platforms for bacterial sensing and NOD2 signalling, Nature, 509, 240, (2014)) proposed a role for SLC15A4 in the activation of NOD2 at the lysosome. Of note, NOD2 mutations are linked to IBD. Dosenovic and coworkers (Dosenovic et al. Slc15a4 function is required for intact class switch recombination to lgG2c in response to TLR9 stimulation. Im- munol Cell Biol, 93, 136, (2015)) find defective endosomal TLR function in pDCs, splenic eDCs and B cells. Furthermore, production of antibodies elicited by a CpGA-adjuvanted vaccine is im- paired in SLC15A4 mice. Griffith and coworkers (Griffith et al. A requirement for slc15a4 in imiquimod-induced systemic inflammation and psoriasiform inflammation in mice, Sci Rep 8, 14451 (2018)) describe a requirement for SLC15A4 in imiquimod-induced systemic inflamma- tion and psoriasiform inflammation in mice. Lopez-Haber and coworkers (Lopez-Haber et al. The phagosomal solute transporter SLC15A4 promotes inflammasome activity via mTORCI signaling and autophagy restraint in dendritic cells, EMBO J, 41 , e111161 (2022)) describe a contribution of SLC15A4 in inflammasome activation via mTORCI signaling pathways.

[0100] It can be further assumed, based on the role of SLC15A4 and / or TASL in IRF5 activation, that the compounds of the present invention will be useful in the treatment or prevention of inflam- matory condition, preferably selected from inflammatory bowel disease, psoriasiform dermatitis, endosomal TLR-dependent inflammation, ulcerative colitis, Crohn’s disease, endosomal TLR-in- duced hyperinflammation, macrophage activation syndrome, allergic airway inflammation, and sarcoidosis, preferably wherein the inflammatory condition is selected from inflammatory bowel disease, psoriasiform dermatitis, and endosomal TLR-dependent inflammation.

[0101] Accordingly, the compounds of the present invention are useful in treatment or prevention of an inflammatory condition.

[0102] Thus, in one embodiment, the present invention relates to the compound of formula (I) or its pharmaceutically acceptable salt, or the pharmaceutical composition of the present invention, for use in treatment or prevention of an autoimmune disorder or an inflammatory condition. In one embodiment, the present invention relates to the compound of formula (I) or its pharma- ceutically acceptable salt, or the pharmaceutical composition of the present invention, for use in treatment or prevention of an autoimmune disorder. In one embodiment, the present invention relates to the compound of formula (I) or its pharmaceutically acceptable salt, or the pharma- ceutical composition of the present invention, for use in treatment or prevention of an inflammat- ory condition.

[0103] The autoimmune disorder is preferably selected from systemic lupus erythematosus, rheumat- oid arthritis, scleroderma, Sjogren’s syndrome, polymyositis / dermatomyositis, primary biliary cir- rhosis, multiple sclerosis, oral ulcers, periodontitis, Behget’s disease, myasthenia gravis, and ankylosing spondylitis. More preferably the autoimmune disorder is systemic lupus erythem- atosus.

[0104] The inflammatory condition is preferably selected from inflammatory bowel disease, psoriasi- form dermatitis, endosomal TLR-dependent inflammation, ulcerative colitis, Crohn’s disease, endosomal TLR-induced hyperinflammation, macrophage activation syndrome, allergic airway inflammation, and sarcoidosis. More preferably, the inflammatory condition is selected from in- flammatory bowel disease, psoriasiform dermatitis, and endosomal TLR-dependent inflamma- tion.

[0105] In one embodiment, the present invention relates to use of the compound of formula (I) or its pharmaceutically acceptable salt, or the pharmaceutical composition of the present invention, in the manufacture of a medicament for use in the treatment or prevention of an autoimmune dis- order or an inflammatory condition. In one embodiment, the present invention relates to use of the compound of formula (I) or its pharmaceutically acceptable salt, or the pharmaceutical com- position of the present invention, in the manufacture of a medicament for use in the treatment or prevention of an autoimmune disorder. In one embodiment, the present invention relates to use of the compound of formula (I) or its pharmaceutically acceptable salt, or the pharmaceutical composition of the present invention, in the manufacture of a medicament for use in the treat- ment or prevention of an inflammatory condition.

[0106] In one embodiment, the present invention relates to the method of treating an autoimmune dis- order, the method comprising administering the compound of formula (I) or its pharmaceutically acceptable salt, or the pharmaceutical composition of the present invention, to a subject in need thereof. It is to be understood that said compound or its salt or said pharmaceutical composition is to be administered in a therapeutically effective amount, preferably as described herein.

[0107] In one embodiment, the present invention relates to the method of treating an inflammatory condition, the method comprising administering the compound of formula (I) or its pharmaceut- ically acceptable salt, or the pharmaceutical composition of the present invention, to a subject in need thereof. It is to be understood that said compound or its salt or said pharmaceutical com- position is to be administered in a therapeutically effective amount, preferably as described herein.

[0108] It is to be noted that the compound of formula (I) or its salt has been shown by the present in- ventors to inhibit SLC15 peptide transporter (i.e. , SLC15A4)-TASL assembly by binding to the SLC15 peptide transporter. Accordingly and preferably, it is expected that the therapeutic effect of the compound of formula (I) or its salt is based on the inhibition of SLC15 peptide transporter (i.e., SLC15A4)-TASL assembly by binding to the SLC15 peptide transporter. Accordingly, in one embodiment the present invention relates to the compound of formula (I) or its salt, or the pharmaceutical composition of the present invention for use in the treatment or prevention of an autoimmune disorder, wherein said compound or said pharmaceutical composition inhibits SLC15 peptide transporter-TASL assembly. Given the ability of the compound of the present in- vention, or its salt, to inhibit the SLC15 peptide transporter-TASL assembly, said compound is particularly useful in the treatment of the autoimmune disorder, wherein the autoimmune dis- order is a disorder associated with SLC15 peptide transporter. Accordingly, the present inven- tion in one embodiment relates to the compound of formula (I) or its salt, or the pharmaceutical composition of the present invention wherein said compound or said pharmaceutical composi- tion for use in the treatment or prevention of an autoimmune disorder, wherein the autoimmune disorder is a disorder associated with SLC15 peptide transporter.

[0109] The compounds provided in the present invention are also useful in treatment or prevention of other lupus diseases such as cutaneous or neonatal lupus erythematosus.

[0110] The invention will be illustrated in the following examples, which however are not to be con- strued as limiting.

[0111] Examples

[0112] List of abbreviations:

[0113] Methods:

[0114] HPLC methods:

[0115] Method A:

[0116] Instrument - Shimadzu Prominance HPLC attached with API 2000 Mass Spectrometer from Ap- plied Biosystems. Ionization method: Electrospray

[0117] UV Wavelength range (nm): 220 and 260

[0118] Solvent A: 10 mM Ammonium Acetate in Water and Solvent B: Acetonitrile

[0119] Flow rate: 1.2 ml / min mobile phase: from 90 % [10 mM Ammonium Acetate in Water] and 10 % [Acetonitrile] to 70% [10 mM Ammonium Acetate in Water] and 30% [Acetonitrile] in 1.50 min, further 10% [10 mM

[0120] Ammonium Acetate in Water] and 90% [Acetonitrile] in 3.00 min, held this mobile phase compo- sition up to 4.00 min and finally back to initial condition in 5.00 min. Type of column: Xbridge C18 (4.6 x 50 mm, 5 micron)

[0121] Mass conditions:

[0122] Ionization technique: ESI (Electron Spray Ionization) using API (Atmospheric pressure loni-za- tion) source.

[0123] Declustering Potential: 50 V

[0124] Mass range: 200-1700 amu

[0125] Scan type: Q1

[0126] Polarity: + / -ve

[0127] Ion Source: Turbo spray

[0128] Ion spray voltage: +5500 for +ve mode and -4500 for -ve mode

[0129] Mass Source temperature: 200 °C.

[0130] Method B:

[0131] Instrument: Waters Acquity H Class LIPLC attached with Waters SQD 2 mass spectrometer. Ionization method: Electro spray

[0132] Capillary (kV) 3.50, Cone (V) 25.00, Source Temperature (°C) 150, Desolvation Tempera-ture (°C) 400, Cone Gas Flow (L / Hr) -50, Desolvation Gas Flow (L / Hr) -750

[0133] Mass range: 100 to 900 Da

[0134] DAD Wavelength range (nm): 200 to 400

[0135] Solvent A: 5 mM NH4OAc in water and Solvent B: 5 mM NH4OAc in ACN: Water (90:10)

[0136] Flow rate: 1.20 ml / min

[0137] (mobile phase: 95% [5 mM NH4OAc in water] and 5% [5 mM NH4OAc in ACN: Water (90:10)] held for 0.75 min, then 85% [5 mM NH4OAc in water] and 15% [5 mM NH4OAc in ACN: Water (90:10) ] in 1.25 min further 70% [5 mM NH4OAc in water] and 30% [5 mM NH4OAc in ACN: Water (90:10) ] in 2.50 min, and finally 2% [5 mM NH4OAc in water] and 98% [5 mM NH4OAc in ACN: Water (90:10) ] in 3.75 min, held this mobile phase composi-tion up to 4.25 min and finally back to initial condition in 4.50 min and held this composi-tion up to 5.10 min).

[0138] TIME Flow Rate (ml / min) %A (5 mM NH4OAc in water) % B (5 mM NH4OAc in ACN: Water (90:10).

[0139] Column Used: Xbridge C18 column (3.5 pm, 50 x 3 mm)

[0140] Column Temperature: 40°C.

[0141] Method C:

[0142] Instrument: Water Acquity H Class UPLC attached with Waters SQD 2 mass spectrometer.

[0143] Ionization method: Electro spray

[0144] Capillary (kV) 3.50, Cone (V) 25.00, Source Temperature (°C) 150, Desolvation Temperature

[0145] (°C) 400, Cone Gas Flow (L / Hr) -50, Desolvation Gas Flow (L / Hr) -750

[0146] Mass range: 100 to 900 Da

[0147] DAD Wavelength range (nm): 200 to 400 Solvent A: 0.05% Formic acid in water and Solvent B: 0.05% HCOOH in ACN: Water (90:10) Flow rate: 0.8 mL / min

[0148] (mobile phase: 95% [0.05% HCOOH in water] and 5% [0.05% HCOOH in ACN: Water (90:10)] held for 0.75 min, then to 75% [0.05% HCOOH in water] and 25% [0.05% HCOOH in ACN: Wa- ter (90:10) ] in 1.5 min, further to 5% [0.05% HCOOH in water] and 95% [0.05% HCOOH in ACN: Water (90:10) ] in 3.00 min, held this mobile phase composition up to 4.00 min and finally back to initial condition in 4.50 min and held this composition up to 5.10 min).

[0149] Column Used: Waters Acquity UPLC BEH C8 (2.1 x 50 mm, 1.7 micron) Column Temperature: 45 °C.

[0150] Method D:

[0151] Instrument: Water Acquity H Class UPLC attached with Waters SQD 2 mass spectrometer. Ionization method: Electro spray

[0152] Capillary (kV) 3.50, Cone (V) 25.00, Source Temperature (°C) 150, Desolvation Temperature (°C) 400, Cone Gas Flow (L / Hr) -50, Desolvation Gas Flow (L / Hr) -750 Mass range: 100 to 900 Da

[0153] DAD Wavelength range (nm): 200 to 400

[0154] Solvent A: 0.05% Formic acid in water and Solvent B: 0.05% HCOOH in ACN: Water (90:10) Flow rate: 0.8 mL / min

[0155] (mobile phase: 95% [0.05% HCOOH in water] and 5% [0.05% HCOOH in ACN: Water (90:10)] held for 1.00 min, then 50% [0.05% HCOOH in water] and 50% [0.05% HCOOH in ACN: Water (90:10) ] in 5.00 min, further to 10% [0.05% HCOOH in water] and 90% [0.05% HCOOH in ACN: Water (90:10) ] in 8.00 min, held this mobile phase composition up to 10.00 min and fi- nally back to initial condition in 11.50 min and held this composition up to 12.00 min). Column Used: Waters Acquity UPLC BEH C8 (2.1 x 50 mm, 1.7 micron)

[0156] Column Temperature: 45 °C.

[0157] Method E:

[0158] Instrument: Shimadzu Prominence HPLC attached with API 2000 Mass Spectrometer from Ap- plied Biosystems.

[0159] Ionization method: Electrospray

[0160] UV Wavelength range (nm): 220 and 260

[0161] Solvent A: 10 mM Ammonium Acetate in Water and Solvent B: Acetonitrile

[0162] Flow rate: 1.2 mL / min mobile phase: from 50 % [10 mM Ammonium Acetate in Water] and 50 % [Acetonitrile] to 5% [10 mM Ammonium Acetate in Water] and 95% [Acetonitrile] in 1.50 min, held this mobile phase composition up to 4.00 min and finally back to initial condition in 5.00 min.

[0163] Type of column: Xbridge C18 (4.6 x 50 mm, 5 micron)

[0164] Mass conditions:

[0165] Ionization technique: ESI (Electron Spray Ionization) using API (Atmospheric pressure Ioniza- tion) source

[0166] Declustering Potential: 50 V

[0167] Mass range: 200-1700 amu

[0168] Scan type: Q1

[0169] Polarity: + / -ve

[0170] Ion Source: Turbo spray

[0171] Ion spray voltage: +5500 for +ve mode and -4500 for -ve mode

[0172] Mass Source temperature: 200 deg C.

[0173] Method F:

[0174] Instrument - Shimadzu Prominance HPLC attached with API 2000 Mass Spectrometer from Ap- plied Biosystems.

[0175] Ionization method: Electrospray

[0176] UV Wavelength range (nm): 220 and 260

[0177] Solvent A: 10 mM Ammonium Acetate in Water and Solvent B: Acetonitrile

[0178] Flow rate: 1.0 ml / min mobile phase: 95 % [10 mM Ammonium Acetate in Water] and 5.00 % [Acetonitrile] held for 0.75 min, then 50% [10 mM Ammonium Acetate in Water] and 50% [Acetonitrile] in 5.00 min, further 5% [10 mM Ammonium Acetate in Water] and 95% [Acetonitrile] in 9.00 min, held this mobile phase composition up to 10.00 min and finally back to initial condition in 11 .00 min and held the initial composition up to 12.00 min .

[0179] Type of column: Xbridge C18 (4.6 x 100 mm, 5 micron)

[0180] Mass conditions:

[0181] Ionization technique: ESI (Electron Spray Ionization) using API (Atmospheric pressure Ioniza- tion) source

[0182] Declustering Potential: 50 V

[0183] Mass range: 200-1700 amu

[0184] Scan type: Q1

[0185] Polarity: + / -ve

[0186] Ion Source: Turbo spray

[0187] Ion spray voltage: +5500 for +ve mode and -4500 for -ve mode Mass Source temperature: 200 deg C.

[0188] Method G:

[0189] Instrument: Waters Acquity H Class LIPLC attached with Waters SQD 2 mass spectrometer. Ionization method: Electro spray

[0190] Capillary (kV) 3.50, Cone (V) 25.00, Source Temperature (°C) 150, Desolvation Temperature (°C) 400, Cone Gas Flow (L / Hr) -50, Desolvation Gas Flow (L / Hr) -750

[0191] Mass range: 100 to 900 Da

[0192] DAD Wavelength range (nm): 200 to 400

[0193] Solvent A: 5 mM NH4OAc in water and Solvent B: 5 mM NH4OAc in ACN: Water (90:10)

[0194] Flow rate: 1.00 ml / min

[0195] (mobile phase: 98% [5 mM NH4OAc in water] and 2% [5 mM NH4OAc in ACN: Water (90:10)] held for 1.00 min, then 50% [5 mM NH4OAc in water] and 50% [5 mM NH4OAc in ACN: Water (90:10) ] in 5.00 min and finally 2% [5 mM NH4OAc in water] and 98% [5 mM NH4OAc in ACN: Water (90:10) ] in 8.00 min, held this mobile phase composition up to 10.00 min and finally back to initial condition in 12.00 min and held this composition up to 12.10 min).

[0196] Column Used: Xbridge C18 column (3.5 pm, 50 x 3 mm)

[0197] Column Temperature: 40°C.

[0198] Method H:

[0199] Instrument: Waters Acquity H Class UPLC attached with Waters QDA mass spectrometer. Ionization method: Electro spray

[0200] Capillary (kV) 0.80, Cone (V) 15.00, Source Temperature (°C) 120, Probe Temperature (°C) 600, Mass range: 100 to 900 Da

[0201] DAD Wavelength range (nm): 200 to 400

[0202] Solvent A: 0.05% Formic Acid in water and Solvent B: ACN

[0203] Flow rate: 1.00 ml / min

[0204] (mobile phase: 98% [0.05% Formic Acid in water] and 2% [ACN] held for 1.00 min, then 40% [0.05% Formic Acid in water] and 60% [ACN] in 4.50 min and finally 5% [0.05% Formic Acid in water] and 95% [ACN] in 9.50 min, held this mobile phase composition up to 13.00 min and fi- nally back to initial condition in 14.00 min and held this composition up to 15.00 min).

[0205] Column Used: Luna Omega Polar C18 column (3.5 pm, 100 x 4.6 mm)

[0206] Column Temperature: 40°C.

[0207] Method J:

[0208] Instrument - Agilent 1260 Infinity II + 6125C SQ

[0209] Ionisation method: Electrospray

[0210] UV Wavelength range (nm): 190 and 400

[0211] Solvent A: Water + 0.1 % Formic acid B: Acetonitrile + 0.1 % Formic acid

[0212] Flow rate: 0.6 ml / min

[0213] Mobile phase: from 90 % [Water + 0.1 % Formic acid ] and 10 % [Acetonitrile + 0.1 % Formic acid] to 90% [Water + 0.1 % Formic acid ] and 10% [Acetonitrile + 0.1 % Formic acid] in 5.00 min, further 10% [Water + 0.1 % Formic acid ] and 90% [Acetonitrile + 0.1 % Formic acid] for 2.00 min.

[0214] Type of column: ZORBAX RRHT StableBond C18, 2.1 x 50 mm, 1.8 pm, 600 bar. 80A

[0215] Mass conditions:

[0216] Ionization technique: ESI (Electron Spray Ionization) using API (Atmospheric pressure Ioniza- tion) source.

[0217] Declustering Potential: 135 V

[0218] Mass range: 50-1500 m / z

[0219] Scan type: Q1

[0220] Polarity: + / -ve

[0221] Ion Source: Turbo spray

[0222] Ion spray voltage: +4000 for +ve mode and -4000 for -ve mode

[0223] Mass Source temperature: 300 °C.

[0224] Method K:

[0225] Waters Acquity H Class LIPLC attached with Waters QDA mass spectrometer.

[0226] Ionisation method: Electro spray

[0227] Capillary (kV) 0.80, Cone (V) 15.00, Source Temperature (°C) 120, Probe Temperature (°C) 600, Mass range: 100 to 900 Da

[0228] DAD Wavelength range (nm): 200 to 400

[0229] Solvent A: 0.05% Formic acid in water and Solvent B: 0.05% HCOOH in ACN: Water (90:10) Flow rate: 0.6 ml / min

[0230] (mobile phase: 95% [0.05% HCOOH in water] and 5% [0.05% HCOOH in ACN: Water (90:10)] held for 0.75 min, then to 75% [0.05% HCOOH in water] and 25% [0.05% HCOOH in ACN: Wa- ter (90:10) ] in 1.5 min, further to 5% [0.05% HCOOH in water] and 95% [0.05% HCOOH in ACN: Water (90:10) ] in 3.00 min, held this mobile phase composition up to 4.00 min and finally back to initial condition in 4.50 min and held this composition up to 5.10 min).

[0231] Column Used: Waters Acquity UPLC BEH C18 (2.1 x 50 mm, 1.7 micron) Column Temperature: 45 °C.

[0232] Mass Source temperature: 200° C.

[0233] Method L: Waters Acquity H Class LIPLC attached with Waters QDA mass spectrometer.

[0234] Ionisation method: Electro spray

[0235] Capillary (kV) 0.80, Cone (V) 15.00, Source Temperature (°C) 120, Probe Temperature (°C) 600, Mass range: 100 to 900 Da

[0236] DAD Wavelength range (nm): 200 to 400

[0237] Solvent A: 0.05% TFA in water and Solvent B: ACN

[0238] Flow rate: 0.40 ml / min

[0239] (mobile phase: 98% [0.05% TFA in water] and 2% [ACN] to 90% [0.05% TFA in water] and 10% [ACN] in 1.50 min, then 60% [0.05% TFA in water] and 40% [ACN] in 18.00 min and finally 5% [0.05% TFA in water] and 95% [ACN] in 19.00 min, held this mobile phase composition up to 20.00 min and finally back to initial condition in 22.00 min and held this composition up to 25.00 min).

[0240] Column Used: Acquity BEH C18 column (1.8 pm, 100 x 2.7mm)

[0241] Column Temperature: 40°C.

[0242] HPLC Methods:

[0243] Method M:

[0244] Reversed phase HPLC was carried out on Agilent 1200 series Instrument with Diode Array De- tector. Column X bridge C18 (5um, 100 x 4.6 mm) with a flow rate of 1.0 ml / min. Two mobile phases were used, mobile phase A: Acetonitrile ; mobile phase C: 10mM ammonium acetate in water, and they were employed to run a gradient conditions Mobile phase from A: 2% [Acetonitrile] and mobile phase B: 98% [10mM ammonium acetate in water] for 0.01 min, Mobile phase from 2% [Acetonitrile] and 98% [10mM ammonium acetate in water] for 1.50 min ,35% [Acetonitrile] and 65% [10mM ammonium acetate in water] for 4.5 min, 95% [Acetonitrile] and 5% [10mM am- monium acetate in water] for 11 min held in this composition up to 13 min for column washing, then returned to initial composition in 14 min and held this condition up to 18.0 min (Total Run time 18.0min). Diluent: DMSO. An injection volume of 2.0ul was used.

[0245] Method N:

[0246] Reversed phase HPLC was carried out on Agilent 1260 infinity 2 series Instrument with Diode Array Detector. Column ACQUITY UPLC BEH C18 (1.7um, 100 x 2.1 mm) with a flow rate of 0.4 ml / min. Two mobile phases were used, mobile phase A: Acetonitrile ; mobile phase C: 0.1 % TFA in water, and they were employed to run a gradient conditions Mobile phase from A: 2% [Acetonitrile] and mobile phase C: 98% [0.1% TFA in water] for 0.00 min, Mobile phase from 10% [Acetonitrile] and 90% [0.1 % TFA in water] for 1.50 min ,40% [Acetonitrile] and 60% [0.1% TFA in water] for 18 min, 95% [Acetonitrile] and 5% [0.1% TFA in water] for 19 min held in this composition up to 20 min for column washing, then returned to initial composition in 22 min and held this condition up to 28 min (Total Run time 28min). Diluent: DMSO. An injection volume of 3 ul was used. NP Preparative HPLC Method:

[0247] Method-prep A:

[0248] Chiral separation was done on Agilent 1200 series instrument. Column name: CHIRALCEL OD- H (250 X 20 mm) 5p. Operating at ambient temperature and flow rate is 18.0 mL / min. Mobile phase was mixture of 80% Hexane, 20% EtOH, held this isocratic mixture run up to 27 min with wavelength of 300 nm.

[0249] Preparation examples: Compounds of the structure (I) can be prepared by a synthesis sequences depicted in the fol- lowing Schemes 1-3.

[0250]

[0251] Scheme 1: Synthesis of intermediates M-3

[0252] Scheme 2: Synthesis of compounds (I) based on amide formation

[0253]

[0254] Scheme 3: Synthesis of compounds (I) based on amide formation and reductive amination (the amine B-4, in particular the unit between the amino group and the acetal / ketal group carrying the optional RS2substituents, provides the R2group of the A moiety of the compounds of for- mula (I).

[0255] Compounds (I) can be prepared starting from an intermediate M-1 which can be converted to different intermediates M-2 by Suzuki couplings using substituted phenyl boronic acids (method A). Alternatively, another coupling reaction suitable to introduce substituted phenyl groups can be used to get to intermediates M-2. Different carboxylic acid intermediates M-3a can be ob- tained by saponification of intermediates M-2.

[0256] Intermediates M-6 can be obtained by Suzuki couplings using an intermediate M-4 and substi- tuted phenyl boronic acids (method B), or an alternative coupling reaction suitable to introduce substituted phenyl groups can be used. Intermediates M-6 can be obtained by using a Negishi coupling to introduce the nitrile group to intermediates M-6 (method C), or an alternative method. Intermediates M-6 can be hydrolyzed to carboxylic acid derivatives M-3b.

[0257] Intermediates M-7 can be deprotonated using n-BuLi at low temperatures in THF and treated with diethyl oxalate (method D) to obtain intermediates M-8. Intermediates M-8 can be reacted with a ketone intermediate K-1 in a condensation reaction (method E) to obtain intermediates M-3c.

[0258] Isatins M-9 can be acylated with different acid chlorides K-2 in pyridine to obtain intermediates M-10. Intermediates M-10 can be reacted with NH4OAc in ethanol at high temperatures (method F) to obtain intermediates M-3d.

[0259] Compounds of the structure (I) can be prepared by a synthesis sequence depicted in Scheme 2 starting from different intermediates M-3. Intermediates M-3 can be reacted with different amines B-1 or B-2 via an amide coupling to obtain compounds (I) respectively. Intermediates M-3 can also be reacted with different amines B-3 which carry a protecting group (e.g. Boc, Cbz, Bn) at the piperidine nitrogen to obtain intermediates M-11 which can be de-protected by a suitable method (method G) to obtain compounds (I) with R6= H. Compounds (I) with R6= H with can then be modified to obtain additional compounds (I) by introduction of a R6(R6other than H) by alkylation with a suitable R6-X (X = Hal, -OMs, -OTs or related; method H) or a re- ductive amination with a suitable aldehyde or ketone (method I). Compounds (I) can be further modified to give additional compounds (I) (e.g. by removing protecting groups, or by introducing additional substituents).

[0260] Additional compounds (I) can be obtained by reaction sequences starting with amide formation of an intermediates M-3 with amines B-4 to obtain intermediates M-12 which, after acetal or ke- tal hydrolysis respectively gives the corresponding aldehyde- or ketone (ketone in the case a suitable substituent RS2is present at the terminal carbon atom of R2: -CRS2(OEt)2) intermediates M-13 (Scheme 3). The intermediates M-13 can be converted to compounds (I) by a reductive amination with amines B-5 (method J).

[0261] Compounds (I) with R2= cyclohexyl, optionally substituted with one or more RS2, can be ob- tained by amide coupling of an M-3 with 4-aminocyclohexan-1-one, or a 4-aminocyclohexan-1- one derivative which is substituted with one or more RS2, followed by a reductive amination with an amine B-5.

[0262] Synthesis of methyl 3-(4-ethoxyphenyl)isoquinoline-1-carboxylate (M-2a-1): - a

[0263] To a stirred solution of methyl 3-chloroisoquinoline-1-carboxylate (M-1a) (1.0 g, 4.52 mmol) in a mixture of dioxane: H2O (4:1) (8.0 mL), was added K3PO4(2.88 g, 13.57 mmol). The mixture was purged with argon for 10 min. 4-ethoxyphenyl) boronic acid (0.9 g, 5.43 mmol) and PdCI2(dtbpf) (0.29 g, 0.45 mmol) were added under argon atmosphere and the mixture was stirred at 80 °C for 3 h. The reaction mixture was cooled to ambient temperature, diluted with a mixture of water (10 mL) and EtOAc (20 mL). The layers separated and the aqueous layer was extracted with EtOAc. Combined organic layer was dried over anhydrous sodium sulfate, sol- vents concentrated under reduced pressure and the residue was purified by Combiflash chro- matography (eluted with 10-20% EtOAc- hexanes) to afford methyl 3-(4-ethoxyphenyl) isoquino- line-1 -carboxylate (M-2a-1).

[0264] LC-MS (Method-A): Rt= 3.93 min; Observed m / z: [M+H]+= 307.9.

[0265] Additional intermediates M-2a are available in an analogous manner using intermediates M-1 and different boronic acids as starting materials. The crude products are purified by chromatog- raphy if necessary (Table Ex1a). Table Ex1a:

[0266] Synthesis of 3-(4-ethoxyphenyl)isoquinoline-1 -carboxylic acid (M-3a):

[0267] To a stirred solution of methyl 3-(4-ethoxyphenyl) isoquinoline-1 -carboxylate (M-2a) (500 mg, 1.63 mmol) in THF: MeOH: H2O (7:3:2) (10.0 mL), was added LiOH H2O (205 mg, 4.88 mmol) and stirred for 16 h at room temperature. The reaction was diluted with water, washed with ethyl acetate, aqueous layer acidified to pH 6 using 1 N aqueous HCI at 0°C. The product was ex- tracted with 10% MeOH in DCM (3 x 10 mL). The combined organic layer was dried over anhy- drous sodium sulfate and solvents were evaporated under reduced pressure to afford 3-(4- ethoxyphenyl) isoquinoline-1-carboxylic acid (M-3a-1).

[0268] LC-MS (Method-B): Rt= 2.09 min; Observed m / z: [M+H]+= 294.2. Additional intermediates M-3a are available in an analogous manner using intermediates M-2a and different boronic acids as starting materials. The crude products are purified by chromatog- raphy if necessary (Table Ex1a).

[0269] Table Ex1b:

[0270] Synthesis of 3-(4-ethoxyphenyl)- / \ / -(3-morpholinopropyl)isoquinoline-1-carboxamide (la-1):

[0271] To a solution of the methyl 3-(4-ethoxyphenyl)isoquinoline-1-carboxylate (M-3a-1) (100 mg, 0.34 mmol) in DMF (3 mL) was added DIPEA (0.18 mL, 1.02 mmol). The mixture was cooled to 0°C and EDC-HCI (131 g, 0.68 mmol), HOBt (51 mg, 0.37 mmol), and the 3-morpholinopropan- 1 -amine (73 mg, 0.51 mmol) were added. The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with H2O (5 mL) and extracted with EtOAc. The com- bined organic layer was dried over anhydrous Na2SO4and concentrated under vacuum, and the residue was purified by RP prep-HPLC to afford 3-(4-ethoxyphenyl)-N-[3-(morpholin-4- yl)propyl]isoquinoline-1-carboxamide (la-1).

[0272] Additional compounds la are available in an analogous manner using intermediates M-3 and dif- ferent amines B-1 as starting materials. The crude products are purified by chromatography if necessary (Table Ex1).

[0273] Table Ex1 :

[0274] Synthesis of / V-(3,3-diethoxypropyl)-3-(4-ethoxyphenyl)isoquinoline-1-carboxamide (M-12-1)

[0275] To a stirred solution of 3-(4-ethoxyphenyl) isoquinoline-1-carboxylic acid (M-3a-1) (1.5 g, 5.11 mmol) in DMF (15 mL) were added 3,3-diethoxypropan-1-amine (1.12 g, 7.67 mmol), Et3N (2.15 mL, 15.35 mmol) and HATU (2.33 g, 6.14 mmol). The reaction mixture was stirred at room tem- perature for 16 h. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic layer was separated, dried over anhydrous sodium sulfate, and the solvents were evaporated. The crude product was purified by combi-flash column chromatography to afford / V- (3,3-diethoxypropyl)-3-(4-ethoxyphenyl) isoquinoline-1-carboxamide (M-12-1).

[0276] Additional intermediates M-12 are available in an analogous manner using intermediates M-3 and different amines B-4 as starting materials. The crude products are purified by chromatogra- phy if necessary (Table Ex2). Table Ex2:

[0277] Synthesis of 3-(4-ethoxyphenyl)- / V-(3-oxopropyl)isoquinoline-1-carboxamide (M-13-1): aqueous HCI, THF

[0278] M-12-1

[0279] To a stirred solution of N-(3,3-diethoxypropyl)-3-(4-ethoxyphenyl) isoquinoline-1 -carboxamide (M-12-1) (200.0 mg, 0.47 mmol) in a mixture of THF:H2O (2:1 , 3 mL), aqueous HCI (2N) (1.4 mL) was added at 25 C and stirred for 2 h at room temperature. Saturated aqueous NaHCO3solution was added to the reaction mixture and extracted with EtOAc (3 x 15 mL), the combined organic layer was washed with brine (2 x 20 mL). The organic layer was dried over anhydrous sodium sulfate and evaporated to afford 3-(4-ethoxyphenyl)-N-(3-oxopropyl) isoquinoline-1 -car- boxamide (M-13-1).

[0280] LC-MS (Method-C): Rt= 3.91 min. Observed m / z: [M+H]+= 348.9. Additional intermediates M-13 are available in an analogous manner using intermediates M-12 starting materials. The crude products are purified by chromatography if necessary (Table Ex3).

[0281] Table Ex3

[0282] Synthesis of (S)-3-(4-ethoxyphenyl)- / \ / -(3-(3-fluoropyrrolidin-1-yl)propyl)isoquinoline-1 -carbox- amide (la-8):

[0283] Et3N, MgSO4,

[0284] NMe4BH(OAc)3,

[0285] CH2CI2

[0286] To a stirred solution of 3-(4-ethoxyphenyl)-N-(3-oxopropyl) isoquinoline-1 -carboxamide (M-13-1) (80 mg, 0.230 mmol, 1.0 equiv.), (S)-3-fluoropyrrolidine (31 mg, 0.345 mmol, 1.5 equiv) and Et3N (2 equiv.) in DCE (2.5 mL) was added anhydrous MgSO4(42 mg 0.345 mmol, 1.5 equiv) and stirred under nitrogen atmosphere at ambient temperature for 1 h. Tetramethylammonium triacetoxyborohydride (121 mg, 0.460, 2.0 equiv.) was added and the reaction mixture stirred at room temperature for 20 h. The reaction mass was filtered over celite, the solvents were evapo- rated under reduced pressure and the residue was purified by RP preparative HPLC to afford (S)-3-(4-ethoxyphenyl)- / V-(3-(3-fluoropyrrolidin-1-yl)propyl)isoquinoline-1-carboxamide (la-8). LC-MS (Method-B): Rt= 2.99 min. Observed m / z: [M+H]+= 422.3

[0287] Additional compounds (I) are available in an analogous manner using intermediates M-13 or compounds la (R6= H) and different amines B-5 as starting materials. The crude products are purified by chromatography if necessary (Table Ex4).

[0288] Table Ex4:

[0289] Synthesis of tert-butyl 4-(3-(4-ethoxyphenyl)isoquinoline-1-carboxamido)piperidine-1-carboxy- late (M-11a-1):

[0290] To a stirred solution of 3-(4-ethoxyphenyl) isoquinoline-1-carboxylic acid (M-3a-1) (1.0 g, 3.41 mmol) in DMF (15 mL) were added / V-(3-dimethylaminopropyl)- / V-ethylcarbodiimide hydrochlo- ride(784 mg, 4.09 mmol, 1.2 equiv.), tert-butyl 4-aminopiperidine-1-carboxylate (683 mg. 3.41 mmol, 1.0 equiv.), DIPEA (1.2 g, 10.2 mmol, 3.0 equiv.) and DMAP (83 mg, 0.68 mmol, 0.2 equiv.). The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was diluted with ethyl acetate and washed with water. The organic layer was separated, dried over anhydrous sodium sulfate, and the solvents were evaporated. The crude product was purified by combi-flash column chromatography to afford tert-butyl 4-(3-(4-ethoxyphenyl)isoquinoline-1- carboxamido)piperidine-1 -carboxylate (M-11-1).

[0291] Synthesis of 3-(4-ethoxyphenyl)- / \ / -(piperidin-4-yl)isoquinoline-1-carboxamide dihydro chloride

[0292] Tert-butyl 4-(3-(4-ethoxyphenyl)isoquinoline-1-carboxamido)piperidine-1-carboxylate (M-11a-1) (970 mg, 1.0 Eq, 2.04 mmol) was dissolved in 3 mL DCM. 4 M HCI in dioxane (10.19 mL, 40.76 mmol, 20 equiv.) was added. The reaction was stirred at rt for 18 h. Another 5 mL of 4M HCI in dioxane were added, and the reaction was stirred at rt for 18 h. The solvent was removed under reduced pressure to give 3-(4-ethoxyphenyl)- / V-(piperidin-4-yl)isoquinoline-1-carboxamide dihy- dro chloride (la-33). Which was purified by RP HPLC to give (la-33).

[0293] Additional compounds (I) are available in an analogous manner using intermediates M-11 or compounds (I) which carry a functional group cleavable under these conditions. The crude prod- ucts are purified by chromatography if necessary (Table Ex5).

[0294] Table Ex5:

[0295] Synthesis of 3-(4-ethoxyphenyl)- / \ / -(1-(2-hydroxyethyl)piperidin-4-yl)isoquinoline-1 -carboxamide (la-37):

[0296] Molecular Weight: 419,53

[0297] To a solution of 3-(4-ethoxyphenyl)- / V-(piperidin-4-yl)isoquinoline-1-carboxamide hydro chloride (la-33) (50 mg, 0.13 mmol, 1.0 equiv.) in 1 mL THF 2-chloroethanol (11 mg, 0.13 mmol, 1.0 equiv.), Nal (20 mg, 0.13 mmol, 1.0 equiv.) and DIPEA (52 mg, 70 pL, 0.40 mmol, 3.0 equiv.) were added, and the reaction was stirred at 50 C for 18 h. Another portion of 2-chloroethanol (11 mg, 1.0 Eq, 0.13 mmol) was added and the reaction was heated to 60 °C and stirred at the same temperature for 18 h. The reaction mixture was diluted with EtOAc (30 mL), washed with water, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude product was purified via flash column chromatography to afford of 3-(4-ethoxyphenyl)- / V-(1-(2-hydrox- yethyl)piperidin-4-yl)isoquinoline-1 -carboxamide (la-37).

[0298] LC-MS (Method-B): Rt= 2.44 min; observed m / z: [M+H]+= 420.3.

[0299] Synthesis of 3-(4-ethoxyphenyl)- / \ / -(1 ,4-dioxaspiro [4.51 decan-8-yl) isoquinoline-1-carboxamide:

[0300] To a stirred solution of 3-(4-ethoxyphenyl) isoquinoline-1-carboxylic acid (1) (500 mg, 1.70 mmol) in DMF (5 mL) were added 3-(4-ethoxyphenyl) isoquinoline-1 -carboxylic acid (294 mg, 1.87 mmol), EDC.HCI (816 mg, 4.26 mmol, HOBt (345 mg, 2.55 mmol) and DIPEA (0.89 mL, 5.30 mmol). The reaction mixture was stirred at room temperature for 24 h. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic layer was separated, dried over anhydrous sodium sulfate and evaporated. The crude product was purified by column chromatography to afford 3-(4-ethoxyphenyl)- / V-(1 ,4-dioxaspiro [4.5] decan-8-yl) isoquinoline-1- carboxamide (LC-MS Method A: Rt= 3.94 min; [M+H]+= 432.9).

[0301] Synthesis of 3-(4-ethoxyphenyl)- / \ / -(4-oxocvclohexyl) isoquinoline-1 -carboxamide:

[0302] To a stirred solution of 3-(4-ethoxyphenyl)- / V-(1 ,4-dioxaspiro [4.5] decan-8-yl) isoquinoline-1-carboxamide (100.0 mg, 0.23 mmol) in THF: H2O (3 ml) at 25°C, HCI (2N in wa- ter) (1.0 mL) was added and stirred at room temperature for 3 h. Saturated NaHCO3aqueous solution was added to the reaction mixture and extracted with ethyl acetate and washed with saturated brine. The organic layer was dried over anhydrous sodium sulphate and the solvent was evaporated to get 3-(4-ethoxyphenyl)- / V-(4-oxocyclohexyl) isoquinoline-1 -carboxamide (LC- MS Method A: Rt= 3.70 min; [M+H]+= 389.1). Synthesis of (S)-3-(4-ethoxyphenyl)- / \ / -(4-(3-hydroxypyrrolidin-1-yl)cyclohexyl)isoquinoline-1-car- boxamide (la-51): MgSO4(37 mg, 0.306 mmol, 2.0 equiv.) and 3-(4-ethoxyphenyl)- / V-(4-oxocyclohexyl) isoquino- line-1 -carboxamide (60 mg, 0.153 mmol, 1.0 equiv.) were added to a solution of (S)-pyrrolidin-S- ol (20 mg, 0.230 mmol, 1.5 equiv.) and triethylamine (46 mg, 0.459 mmol, 3.0 equiv.) in DCE (3 mL) at room temperature and stirred for 1 hour under N2atmosphere. Tetramethylammonium triacetoxyborohydride (81 mg, 0.306 mmol, 2.0 equiv.) was added and the reaction mixture was stirred at room temperature for 20 hours. The reaction mixture was filtered and evaporated. Crude compound was purified by RP prep. HPLC to obtain la-51 as a mixture of c / s and trans isomers.

[0303] Compound la-52 as a mixture of cis and trans isomers can be synthesized in an analogous manner using 3-(4-ethoxyphenyl)- / V-(4-oxocyclohexyl) isoquinoline- 1 -carboxamide and (R)- pyrrolidin-3-ol as starting materials. The crude products are purified by RP prep. HPLC (Table Ex5a). Additional analogs can be obtained by using the same method using different carboxylic acids and different amines.

[0304] Table Ex5a:

[0305]

[0306] In an oven dried 50 mL screw cap sealed tube charged with a magnetic stirrer bar, 6-bromo-8- chloroisoquinoline (M-4-1) (200 mg, 0.83 mmol), (4-ethoxyphenyl)boronic acid (179 mg, 1.08 mmol) and K3PO4(352 mg, 1.66 mmol) were dissolved in 10 mL dioxane:water (5:1). The reac- tion mixture was purged with N2for 15 minutes. PdCI2(dtbpf) (54 mg, 0.08 mmol) was added un- der nitrogen atmosphere to the reaction mixture. The reaction mixture was heated to 80C and stirred at this temperature for 5 h. To the reaction mixture was added 20 mL ethyl acetate and 20 mL water and the phases were separated. The aqueous layer was extracted with ethyl ac- etate. The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, concentrated, and purified combi-flash column chromatography (using 5% to 10% EtOAc in hexanes) to afford 8-chloro-6-(4-ethoxyphenyl) isoquinoline (M-5-1).

[0307] LC-MS (Method-B): Rt= 3.17 min; observed m / z: [M+H]+= 284.1.

[0308] Synthesis of 6-(4-ethoxyphenyl)isoquinoline-8-carbonitrile (M-6-1):

[0309] In an oven dried 50 mL sealed tube charged with a magnetic stirrer bar, 8-chloro-6-(4- ethoxyphenyl) isoquinoline (M-6-1) (390 mg, 1.37 mmol) and Zn(CN)2(403 mg, 3.43 mmol) were dissolved in of 13 mL anhydrous DMAc. The reaction mixture purged with nitrogen for 15 minutes. Zn (90 mg, 1.37 mmol) and Pd(dppf)CI2DCM were added under nitrogen atmosphere, the reaction mixture was heated to 165C and stirred at this temperature for 16 h. To the reaction mixture was added 20 mL ethyl acetate and 30 mL water and the phases were separated. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with ice-cold brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by combi-flash chromatography (using 15% to 20% EtOAc in hexanes) to afford 6- (4-ethoxyphenyl) isoquinoline-8-carbonitrile (M-6-1).

[0310] LC-MS (Method-C): Rt= 3.23 min. Observed m / z: [M+H]+= 275.3.

[0311] Synthesis of 6-(4-ethoxyphenyl)isoquinoline-8-carboxylic acid (M-3b-1):

[0312] In 100 mL round bottom flask charged with a magnetic stirrer bar, was added 6-(4- ethoxyphenyl) isoquinoline-8-carbonitrile (M-6-1) (400 mg, 1.56 mmol). A mixture of MeOH: H2O (1 :1 , 15 mL) was added followed by the addition of KOH (246 mg, 4.38 mmol). The reaction mixture was heated to reflux and stirred for 16 h under reflux. The solvents were removed under vacuum and the residue was dissolved in 30 mL of water and washed with dichloromethane. The aqueous layer was cooled with an ice bath and was acidified by addition of 1(N) HCI (pH ~ 5). The mixture was extracted with a mixture of 20% IPA in DCM. The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated to afford 6-(4- ethoxyphenyl) isoquinoline-8-carboxylic acid (M-3b-1).

[0313] LCMS (Method B): Rt= 2.06 min. Observed m / z: [M+H]+= 294.2.

[0314] Synthesis of 6-(4-ethoxyphenyl)-N-(3-morpholinopropyl)isoquinoline-8-carboxamide (Id-1):

[0315] In an oven dried 25 mL round bottom flask charged with a magnetic stirrer bar, 6-(4- ethoxyphenyl) isoquinoline-8-carboxylic acid (M-3b-1) (75 mg, 0.26 mmol, 1 equiv.) was taken in anhydrous DMF (10 mL / mmol) under nitrogen atmosphere. HATU (0.65 mmol, 2.5 equiv.) was added in one portion followed by drop-wise addition of DIPEA (1.3 mmol, 5 equiv. )The re- action mixture was stirred at room temperature for 5 minutes. 3-morpholinopropan-1- amineamine (0.39 mmol, 1.5 equiv.) was added and the reaction mass was stirred at room tem- perature for 16h. The reaction mixture diluted with a mixture of 10% MeOH in DCM (20 mL) and water (20 mL) and the phases were separated. The aqueous layer was extracted with 10% MeOH in DCM. The combined organic layer was washed with ice-cold brine, dried over sodium sulfate, concentrated, and purified by RP preparative HPLC to afford [6-(4-ethoxyphenyl)-N-(3- morpholinopropyl) isoquinoline-8-carboxamide] (Id-1).

[0316] Additional compounds Id are available in an analogous manner using intermediates M-3b and different amines B1 as starting materials (Table Ex6). The crude products are purified by chro- matography if necessary.

[0317] Table Ex6:

[0318] Synthesis of 2-(4-ethoxyphenyl)-1 ,8-naphthyridine-4-carboxylic acid (M-3c-1):

[0319] M-3C-1

[0320] M-8a-1 To a stirred solution of ethyl 2-[2-(2,2-dimethylpropanamido) pyridin-3-yl]-2-oxoacetate (M-3c-1) (550 mg, 1.98 mmol) in ethanol (16 mL) and water (4 mL), KOH (465 mg, 8.30 mmol) was added and the reaction mixture was refluxed for 2 h. Then 1-(4-ethoxyphenyl) ethan-1-one (K-1- 1) (681 mg, 4.15 mmol, 2.1 equiv.) was added to the reaction mixture and the mixture was re- fluxed for 16 h. The reaction mixture was concentrated under reduced pressure. The residue was diluted with water (20 mL) and extracted with EtOAc. The aqueous layer was cooled with an ice bath and the pH was adjusted to~5 by carful addition of 2(N) aqueous HCI. The aqueous phase was extracted with a mixture of 10% MeOH in DCM. The combined organic layer was dried over anhydrous sodium sulfate and solvents were evaporated under reduced pressure to afford 2-(4-ethoxyphenyl)-1,8-naphthyridine-4-carboxylic acid (M-3c-1). LC-MS (Method-B): Rt= 1.76 min. Observed m / z: [M+H]+= 295.1.

[0321] Synthesis of methyl 2-(4-ethoxyphenyl)-1 ,6-naphthyridine-4-carboxylic acid (M-3c-4):

[0322] To a stirred solution of ethyl 2-[4-(2,2-dimethylpropanamido) pyridin-3-yl]-2-oxoacetate (M-8b-1) (600 mg, 2.16 mmol) in EtOH: H2O (4:1) (20 mL), was added KOH (483 mg, 8.63 mmol) and re- fluxed for 2h. 1-(4-ethoxyphenyl) ethan-1-one (K-1-1) (743 mg, 4.52 mmol) was added and the reaction mixture was refluxed for an additional 16 h. The reaction mixture was concentrated un- der vacuum. Water was added and the mixture was washed with EtOAc and the phases were separated. The aqueous layer was acidified to pH 6 by addition of 2 N aqueous HCI solution at ice bath temperature. The resulting precipitate was filtered and dried under vacuum to afford 2- (4-ethoxyphenyl)-1 ,6-naphthyridine-4-carboxylic acid (M-3c-4).

[0323] LC-MS(Method-A): Rt= 2.48 min. Observed m / z: [M+H]+= 295.3.

[0324] Synthesis of methyl 2-(4-ethoxyphenyl)- / \ / -r3-(morpholin-4-yl) propyl1-1 ,6-naphthyridine-4-car- boxamide (lc-1):

[0325] To a solution of the 2-(4-ethoxyphenyl)-1 ,6-naphthyridine-4-carboxylic acid (M-3c-4) (100 mg, 0.34 mmol) in DMF (3 mL) was added DIPEA (0.18 mL, 1.02 mmol). The mixture was cooled to 0°C and EDC-HCI (131 g, 0.68 mmol), HOBt (51 mg, 0.37 mmol), and the 3-morpholinopropan- 1-amine (73 mg, 0.51 mmol) were added. The reaction was stirred at room temperature for 16 h. The reaction mixture was poured into H2O (10 mL) and extracted with EtOAc. The combined organic layer was dried over anhydrous Na2SO4and concentrated under vacuum. The residue was purified by RP preparative HPLC to afford 2-(4-ethoxyphenyl)- / V-[3-(morpholin-4-yl)propyl]- 1 ,6-naphthyridine-4-carboxamide (lc-1).

[0326] Additional compounds la are available in an analogous manner using intermediates M-3c and different amines B-1 as starting materials. The crude products are purified by chromatography if necessary (Table Ex7).

[0327] Table Ex7:

[0328] Synthesis of methyl 2-(4-ethoxyphenyl)-1 ,7-naphthyridine-4-carboxylic acid (M-3c-5):

[0329] Ethyl 2-oxo-2-(3-pivalamidopyridin-4-yl) acetate (M-8c-1) (0.7 g, 2.52 mmol) was dissolved in a mixture of 4:1 EtOH / water (28 mL). The reaction mixture was heated to refluxed under nitrogen atmosphere and stirred under reflux for 2 h. 1-(4-ethoxyphenyl) ethan-1-one (K-1-1) (868 mg, 5.29 mmol, 2.1 equiv.) was added, and the solution was refluxed for another 24 h. The solvents were removed under vacuum and the residue was dissolved in 30 mL water and washed with CH2CI2. The aqueous phase was acidified by addition of aqueous 1 N HCI and extracted with a mixture of 20% IPA in DCM. The combined organic layer was washed with brine, dried over an- hydrous sodium sulfate and, concentrated to afford 2-(4-ethoxyphenyl)-1 ,7-naphthyridine-4-car- boxylic acid (M-3c-5).

[0330] LC-MS (Method C): Rt= 2.45 min. Observed m / z: [M+H]+= 295.3.

[0331] Additional compounds M-3c are available in an analogous manner using intermediates M-8c and / or different amines B-1 as starting materials. The crude products are purified by chromatog- raphy if necessary.

[0332] Synthesis of 2-(4-ethoxyphenyl)- / \ / -(3-morpholinopropyl)-1 ,7-naphthyridine-4-carboxamide1 (If- IX

[0333] 2-(4-ethoxyphenyl)-1,7-naphthyridine-4-carboxylic acid (M-3c-5) (110 mg, 0.375 mmol, 1 equiv) was dissolved in anhydrous DMF (4 mL) under nitrogen atmosphere. HATLI (356 mg, 0.938 mmol, 2.5 equiv.) was added in one portion followed by drop-wise addition of DI PEA (646 mg, 1.875 mmol, 5 equiv.) and the reaction mixture was stirred at room temperature for 5 min. 3- morpholinopropan-1-amine (81 mg ,0.563 mmol, 1.5 equiv.) was added, and the reaction mix- ture was heated to 60°C and stirred at this temperature for 16 h. A mixture of 10% MeOH in DCM (20 mL) was added to the reaction mixture. The resulting organic phase was washed with water. The aqueous layer was extracted with a mixture of 10% MeOH in DCM. The combined organic layer was washed with ice-cold brine, dried over sodium sulfate, concentrated, and the residue was purified by RP preparative HPLC to afford [2-(4-ethoxyphenyl)- / V-(3-morpholino- propyl)-1,7-naphthyridine-4-carboxamide] (lf-1).

[0334] Additional compounds If are available in an analogous manner using intermediates M-3 and dif- ferent amines B1 as starting materials. The crude products are purified by chromatography if necessary (Table Ex8).

[0335] Table Ex8:

[0336] Synthesis of methyl 1-(4-ethoxybenzoyl) indoline-2, 3-dione (M-10-1): An oven dried two neck 100 mL round bottom flask was charged with a magnetic stirrer bar and isatin (M-9-1) (500 mg, 3.4 mmol). 7.5 mL of anhydrous pyridine was added under nitrogen at- mosphere and the reaction mixture was cooled in an ice-bath. 4-Ethyoxybenzoyl chloride (0.68 mL, 4.42 mmol) was added drop-wise. Upon completion of addition, the reaction mixture was slowly allowed to warm to room temperature and heated at 60 °C afterwards. The reaction mix- ture was stirred at 60°C for 2h. The reaction mixture was cooled (ice-bath) and neutralize by ad- dition of 1 N aqueous HCI to pH ~ 7. Water was added to the mixture, the phases were sepa- rated, and the aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over sodium sulfate, concentrated followed by azeotropic distillation with toluene to afford 1-(4-ethoxybenzoyl) indoline-2, 3-dione (M-10-1) which was used in the next step without further purification.

[0337] Additional intermediates M-10 are available in an analogous manner using different intermedi- ates M-9 and / or different acid chlorides K-2 as starting materials. The crude products are puri- fied by chromatography if necessary (Table Ex9).

[0338] Table Ex9: Synthesis of 2-(4-ethoxyphenyl) quinazoline-4-carboxylic acid (M-3d-1):

[0339] 1-(4-ethoxybenzoyl) indoline-2, 3-dione (M-10-1) (500 mg, 1.69 mmol) was added to a oven dried sealed tube. Ammonium acetate (1.3 g, 16.93 mmol) was added followed by anhydrous ethanol (5 mL). The reaction mixture was heated in a pre-heated oil bath at 100 °C under vigor- ous stirring and stirred at this temperature for 16 h. The organic solvent was evaporated, and the solid residue was dissolved in water. The aqueous layer was acidified (pH ~ 5) by addition of 1 N aqueous HCI under cooling (ice-bath) and extracted with a mixture of 20% isopropanol in DCM. The combined organic layer was washed with brine, dried over sodium sulfate, concen- trated and the residue was purified by combi-flash chromatography using 0-20% MeOH in DCM as eluent to afford 2-(4-ethoxyphenyl) quinazoline-4-carboxylic acid (M-3d-1).

[0340] Additional compounds in table M-3d are available in an analogous manner using different inter- mediates M-10 as starting materials. The crude products are purified by chromatography if nec- essary (Table Ex10).

[0341] Table Ex10:

[0342] Synthesis of 2-(4-ethoxyphenyl)- / \ / -(3-morpholinopropyl) quinazoline-4-carboxamide (lb-1):

[0343] To a stirring solution of 2-(4-ethoxyphenyl) quinazoline-4-carboxylic acid (M-3d-1) (70 mg, 0.24 mmol) in HPLC grade acetonitrile (2.5 mL) were sequentially added chloro- / V, A / , A / , / V'-tetram- ethylformamidinium hexafluorophosphate (666 mg, 2.37 mmol, 10 equiv.) and 3-morpholino- propan-1 -amine (0.087 mL, 0.59 mmol) under nitrogen atmosphere. DIPEA (0.83 mL, 4.75 mmol, 20 equiv.) was added dropwise and the resulting reaction mixture was stirred at 65°C for 16 h. The reaction mixture was partitioned between a mixture of 10% MeOH in DCM (30 mL) and water (30 mL). The aqueous part was extracted with a mixture or 10% MeOH in DCM (3 x 30 mL). The combined organic layer was washed with brine, dried over anhydrous sodium sul- fate, concentrated, and purified by RP preparative HPLC to afford 2-(4-ethoxyphenyl)- / V-(3-mor- pholinopropyl) quinazoline-4-carboxamide (lb-1).

[0344] Additional compounds lb are available in an analogous manner using different carboxylic acid derivatives M-3d and / or different amines B-1 as starting materials. The crude products are puri- fied by chromatography if necessary (Table Ex11).

[0345] Table Ex11 :

[0346] Synthesis of NanoBRET probe (Probel):

[0347] Synthesis of 2-(4-ethoxyphenyl)- / \ / -(4-(4-(6-((7-nitrobenzorcin,2,51oxadiazol-4-yl)amino)hex- anoyl)piperazin-1-yl)butyl)quinoline-4-carboxamide (Probel):

[0348]

[0349] To a solution of 2-(4-ethoxyphenyl)- / V-(4-(piperazin-1-yl)butyl)quinoline-4-carboxamide-2HCI (51 mg, 0.1 mmol, 1 equiv.), 6-((7-nitrobenzo[cj[1,2,5]oxadiazol-4-yl)amino)hexanoic acid (44 mg, 0.15 mmol, 1.5 equiv.) and DIPEA (51 mg, 4 equiv.) in dry DMF (3 mL) was added HATLI (57 mg, 0.15 mmol, 1.5 euquiv.) and the reaction mixture was stirred for 18 hours at rt. The reaction solution was diluted with DCM (35 mL) and then washed with saturated aqueous NaHCO3solu- tion. (35 mL) twice. The organic layer was washed with brine (40 mL), separated in a funnel, and dried over MgSO4, filtered and the solvents were evaporated. The crude product was puri- fied by normal phase chromatography using prepacked column Chromabond 25 g silica with the gradient eluent (EtOAc / MeOH(1% Et3N)) to afford 2-(4-ethoxyphenyl)- / V-(4-(4-(6-((7-ni- trobenzo[c][1,2,5]oxadiazol-4-yl)amino)hexanoyl)piperazin-1-yl)butyl)quinoline-4-carboxamide (Probel). Observed m / z: [M+H]+= 709.5 Rt=7.13 (LC-MS method J)

[0350] To a solution of tert-butyl 4-(4-(2-(4-ethoxyphenyl)quinoline-4-carboxamido)butyl)piperazine-1- carboxylate (93 mg, 0.17 mmol) in 10 ml of dichloromethane was added 1 mL HCI (4N in diox- ane) and the reaction mixture was stirred for 3 h, formation of white precipitate was observed. The reaction mixture was reduced to a smaller volume and 10 ml of diethyl ether was added, the resulting precipitate was filtered off and dried under vacuum to give 2-(4-ethoxyphenyl)- / V- (4-(piperazin-1-yl)butyl)quinoline-4-carboxamide-2HCI (51 mg, 0.1 mmol).

[0351] To a cooled to 0 °C solution of 2-(4-ethoxyphenyl)- / V-(4-hydroxybutyl)quinoline-4-carboxamide (182 mg, 0.5 mmol, 1 Eq) in 5 ml of dry dichloromethane was added methanesulfonyl chloride (80 mg, 0.7 mmol, 1.4 Eq) in 1 ml of dry dichloromethane followed by the addition of triethyl amine (101 mg, 1 mmol, 2 Eq) in 1 ml of dry dichloromethane and the reaction mixture was stirred for 2 hours at 0 °C. After the completed conversion, the reaction mixture was filtered and evaporated to obtain the crude 4-(2-(4-ethoxyphenyl)quinoline-4-carboxamido)butyl methane- sulfonate in quantitative yield. The crude material was dissolved in 10 ml of acetonitrile and tert- butyl piperazine-1-carboxylate (558 mg, 3 mmol, 6 Eq) was added in a single portion followed by the addition of potassium carbonate (276 mg, 2 mmol, 4 Eq). The reaction mixture was stirred at 60 °C for 18 h and the evaporated till dryness. The residue was diluted with DCM (50 mL) and then washed with NaHCO3aq. (35 mL) twice. The organic layer was washed with brine (40 mL), separated in a funnel, and dried over MgSO4, filtered and evaporated. The crude prod- uct was purified by normal phase chromatography using prepacked column Chromabond 25 g silica with the gradient eluent (EtOAc / MeOH(1 % Et3N)) to tert-butyl 4-(4-(2-(4- ethoxyphenyl)quinoline-4-carboxamido)butyl)piperazine-1-carboxylate (93 mg, 0.17 mmol) as brownish oil.

[0352] To a solution of 2-(4-ethoxyphenyl)quinoline-4-carboxylic acid (293 mg, 1 mmol, 1 Eq), 4- aminobutan-1-ol (120 mg, 1.35 mmol, 1.35 Eq) and DIPEA (258 mg, 2 Eq) in dry DMF (7 mL) was added HATU (450 mg, 1.18 mmol, 1.18 Eq) and the reaction mixture was stirred for 18 hours at 20 °C. The reaction solution was diluted with DCM (35 mL) and then washed with NaHCO3aq. (35 mL) twice. The organic layer was washed with brine (40 mL), separated in a funnel, and dried over MgSO4, filtered and evaporated. The crude product was purified by nor- mal phase chromatography using prepacked column Chromabond 25 g silica with the gradient eluent (EtOAc / MeOH(1% Et3N)) to 2-(4-ethoxyphenyl)-N-(4-hydroxybutyl)quinoline-4-carbox- amide (321 mg, 0.88 mmol) as an off-white powder.

[0353] Biological data

[0354] Biological example 1 : TASL proteostasis by TASL-EmGFP-P2A-mCherry (TGC) reporter

[0355] The TGC reporter construct encodes C-terminally EmGFP-tagged TASL followed by the P2A self-cleaving peptide and mCherry (SEQ ID NO:01), enabling constitutive expression of both ORFs from the same promoter. The measurement of EmGFP to mCherry fluorescence ratio al- lows the monitoring of TASL-EmGFP intracellular levels by microscopy imaging.

[0356] 2k HEK-293T cells stably overexpressing the TGC reporter and N-terminally HA-tagged SLC15A4 (SEQ ID NO:02) were generated by genomic integration of a lentiviral construct carry- ing the sequence of the TGC reporter and a separate genomic integration of a lentiviral con- struct carrying the HA-SLC15A4 sequence. The cells were seeded in DMEM media with 10% FBS (Gibco # 11965092, Fisher Scientific, cat. #11550356) and 1% Pen-Strep (Sigma-Aldrich cat. #P4333) in 384-well plates (Perkin Elmer, cat. #8693-22361) previously coated with poly-ly- sine (Sigma-Aldrich, cat. #P6282). Right after seeding, compounds were added at final concen- trations of 4 pM and 14 pM, respectively, by Tecan D300e Digital Dispenser. 1% DMSO was used as negative control to normalize the data per plate. Each compound was measured in two independent biological replicates and each replica had three technical measurements. After 48h of incubation at 37 degrees and 5% of CO2, Hoechst 33342 dye (Fisher Scientific, cat. #62249) was added at 5 pM final. Each plate was spun down and then incubated for 10 minutes at room temperature (RT). Next, media was removed and 2% Paraformaldehyde (PFA) was added to the cells. The plate was incubated again for 20 minutes at RT and then two washing steps with Dulbecco’s Phosphate Buffered Saline (PBS, Sigma-Aldrich, cat. # D8537) were performed. Fi- nally, 30pl of PBS was added to the wells and the plates were sealed and stored at 4 degrees until being imaged.

[0357] Microscopy images were acquired on Operetta CLS High Content Analysis System with a 20x water objective (1.0 NA) using Harmony 5.1 software (PerkinElmer / Revvity). Exposure settings for Hoechst, mCherry and EmGFP channels were adjusted to avoid image saturation. Following acquisition, images were subjected to analysis via an analysis / segmentation sequence imple- mented on Harmony 5.1. The latter involved identifying cell nuclei and cytosolic regions, on Hoechst and EmGFP / mCherry channels, respectively. Total cell fluorescent intensity values were derived for both EmGFP and mCherry channels in a population of cells excluding image artifacts and outliers, such as false positive cells and debris. Averaged EmGFP / mCherry ratios per field are reported in Table BiolEx-1. Figure 1 shows examples of microscopy images using the assay with Example lc-8.

[0358] The assay of the present example allows for the monitoring of changes in protein levels of TASL upon compound treatment, with active compounds being able to reduce the EmGFP / mCherry ratio (a ratio of 0 is understood as no detectable TASL protein).

[0359] The ratios were defined as follows in Table BiolEx-1: +++: EmGFP / mCherry ratio between 0 and 0.4 ++: EmGFP / mCherry ratio between 0.41 and 0.7 +: EmGFP / mCherry ratio between 0.71 and 0.99.

[0360] Biological example 2: NanoBRET binding assay A GGGGS linker (SEQ ID NO:04) was inserted immediately downstream of T358 (in the loop E353-T363) followed by a full-length NanoLuc sequence (SEQ ID NO:03) using Gibson cloning. Additionally, the N-terminal region of SLC15A4 containing a lysosomal targeting LL motif was deleted (amino acids 2-29). The full sequence of this construct can be found in SEQ ID NQ:05. Lentiviral transduction was used to generate a stable SLC15A4-overexpressing HAP1 cell line. The underlying HAP1 cell line was from Horizon Discovery #C669.

[0361] For the measurement of NanoBRET (Machleidt et al., NanoBRET- A Novel BRET Platform for the Analysis of Protein-Protein Interactions, ACS Chem. Biol. 2015), HAP1 cells overexpress- ing the above-described construct were plated at 60k / well in 96well plates (Corning #CLS3904) with 100ml / well of IM DM media (Gibco #12440053) with 10% FBS (Fisher Scientific, cat. #11550356) and 1% Pen-Strep (Sigma-Aldrich cat. #P4333). The day after plating, the IMDM medium was replaced with 30pl of OPTIMEM (Thermo Fisher, 31985062) containing Vivazine (1:200 dilution, Promega, #N2581) and a compound to be tested was added at final concentra- tion of 3 pM and 12.5 pM, respectively. Control wells were treated with the same solution con- taining DMSO at the same final % of the highest compound treatment. Plates were incubated for 1h at 37°C, 5 %CO2and the plate measured on a Tecan Spark instrument spanning two spectral ranges: 450-475 nm for Nanoluc (“Donor”) emission and 520-545 nm for NBD (“Accep- tor”, 4-nitro-7-aminobenzofurazan) emission (the “no acceptor” plate reading). Then, Probel, which is the fluorescent acceptor (see Synthesis of NanoBRET probe (Probel) above for the synthesis and structure of the fluorescent acceptor) was added at a final concentration of 20 pM and the plate was incubated at 37°C, 5%CO2 for 10 min. Then, the plate was measured again as described above: on a Tecan Spark instrument spanning two spectral ranges: 450-475 nm for Nanoluc emission and 520-545 nm for NBD emission (the “with acceptor” plate reading).

[0362] NanoBRET arbitrary units were calculated by dividing the electronic counts of the NBD emission over the electronic counts of the Nanoluc emission. The NBD / Nluc ratio from the “no acceptor” reading was subtracted from the “with acceptor” reading for the purposes of normalization. The result was multiplied by 1000 thus giving values in milliBRET units (mBU).

[0363] BRET mBU = (NBD / Nanoluc)w# / 7 acceptor- (NBD / Nanoluc)no acceptor

[0364] Since Probel binds to SLC15A4, increased concentration of Probel results in the increase in BRET signal as shown in Figure 2.

[0365] For a given compound, BRET mBUs were normalized against the DMSO readout to give the re- sults shown in Table BiolEx-2 below. Compounds resulting in a reduced BRET signal displace the fluorescent acceptor (Probel) and therefore bind to SLC15A4 in a conformation that pre- vents the binding of TASL.TASL is predicted to bind to SLC15A4 in the inward facing conforma- tion (Custodio et al, Molecular basis of TASL recruitment by PHT1 , Nature Communications, 2023).

[0366] Table BiolEx-2:

[0367] The normalized BRET signals were defined as follows in Table BiolEx-2: +++: Normalized BRET signal between 0 and 0.6 ++: Normalized BRET signal between 0.61 and 0.8 +: Normalized BRET signal between 0.81 and 0.99.

[0368] Biological example 3: Enzyme-linked immunosorbent assay (ELISA)

[0369] IRF5 activation downstream of the SLC15A4 / TASL signalling complex results in the production and secretion of proinflammatory cytokines including interleukin-6 (IL-6) and tumor-necrosis fac- tor alpha ( TN Fa) (Heinz et al. 2020, Takaoka et al. 2005). Cytokine production can be moni- tored by ELISA, an assay well known to the skilled person.

[0370] Peripheral Blood Mononuclear Cells (PBMCs) from human healthy donors were purified from whole blood by density centrifugation (Ficoll-Paque, Fisher Scientific, cat. #11768538), washed twice with PBS (Sigma-Aldrich, cat. #D8537) and were frozen in Fetal Bovine Serum (FBS, Fisher Scientific, cat. #11550356) plus 10% DMSO (as freezing media) until further use. For compound treatment, PBMCs were thawed in RPMI 1640 media (Gibco cat. #12004997) con- taining 10% FBS and counted. 100k PBMCs per well were seeded in 96-well transparent or black plates (Corning Costar, Fisher Scientific, cat. #10687551 ; Corning Costar, Sigma Aldrich, cat. #CLS3904-100EA) and compounds at a serial concentration from 50 pM to 0.6 nM were added in technical triplicates, and plates were incubated at 37 degrees and 5% of CO2 for 48h. 20h before readout, cells were stimulated with 5pg / mL Resiquimod (R848, MedChem Express, cat. #HY-13740). At the end of the stimulation period, plates were spun down at 250g for 5 min- utes and supernatants were collected and analyzed for IL-6 and TNFa cytokine levels by ELISA (Invitrogen, cat. #88-7066-88 and 88-7346-88) according to manufacturer’s instructions.

[0371] Treatment of PBMCs with compounds, which are able to the interfere with the SLC15A4 / TASL complex (thus interfering with the pathway that would ultimately result in IRF5 activation, which leads to cytokine production), is expected to result in reduced cytokine production. Data for the tested examples is shown in Table BiolEx-3 for IL-6 and in Table BiolEx-4 for TNFa in below. Table BiolEx-3:

[0372] The IL-6 reduction was defined as follows in Table BiolEx-3:

[0373] +++: Normalized IL-6 concentration compared to DMSO treatment between 0 and 0.4 ++: Normalized IL-6 concentration compared to DMSO treatment between 0.41 and 0.7

[0374] +: Normalized IL-6 concentration compared to DMSO treatment between 0.71 and 0.99.

[0375] Table BiolEx-4:

[0376] The IL-6 reduction was defined as follows in Table BiolEx-3:

[0377] +++: Normalized TNFa concentration compared to DMSO treatment between 0 and 0.4

[0378] ++: Normalized TNFa concentration compared to DMSO treatment between 0.41 and 0.7

[0379] +: Normalized TNFa concentration compared to DMSO treatment between 0.71 and 0.99.

[0380] In particular, the present invention relates to the following items:1. A compound of formula (I) or a stereoisomer, tautomer, N-oxide, pharmaceutically acceptable salt or solvate thereof, wherein: R1is phenyl sS1Su 1bstituted with one or more R ;wherein each R is independently selected from -Hal, C1-6 alkyl, C1-6 haloalkyl, -cycloalkyl,-O(C1-6alkyl), -O(C1-6haloalkyl), and -NH-CO(C1-6alkyl); or two RS1together form a fused hete- rocycloalkyl or heteroaryl moiety;A is a moiety selected from wherein the wavy line in each case marks the connection to the remainder of the molecule; and wherein:R2 is C2-4 alkylene or C6 cycloalkylene, each optionally substituted with one or more RS2;wherein each RS2is independently selected from -OH, -F, and -CH3; or two RS2together form =O; each R3is independently selected from -H, C1-5alkyl, -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)- heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-heteroaryl, each optionally substitutedwith one or more RS3; provided that not both R3 are -H;or the two R3together with the nitrogen atom to which they are attached form a heterocycloalkyl ring, optionally substituted with one or more RS3; wherein each RS3is independently selected from -CN, -Hal, -OH, -NH2, -NH(C1-6alkyl), -N( C1-6alkyl)(C1-6alkyl), C1-6alkyl, C1-6haloalkyl, -(C1-6alkylene)-CN, -(C1-6alkylene)-OH, -(C1-6alky-lene)-NH(C1-6 alkyl), -(C1-6 alkylene)-N(C1-6 alkyl)(C1-6 alkyl), -O(C1-6 alkyl), -O(C1-6 haloalkyl),-(C1-6alkylene)-O(C1-6alkyl), -S(C1-6alkyl), -S(C1-6haloalkyl), -(C1-6alkylene)-S(C1-6alkyl), -COH, -CO(C1-6alkyl), -CO(cycloalkyl), -CO(heterocycloalkyl), -COOH, -COO(C1-6alkyl), -CO-NH2, -CO-NH(C1-6alkyl), -CO-N(C1-6alkyl)(C1-6alkyl), -NH-CO(C1-6alkyl), -N(C1-6alkyl)-CO(C1-6alkyl), -S(O)2-(C1-6alkyl), -S(O)2-NH2, -S(O)2-NH(C1-6alkyl), -S(O)2-N(C1-6alkyl)(C1-6alkyl), -NH-S(O)2-(C1-6 alkyl), -N(C1-6 alkyl)-S(O)2-(C1-6 alkyl), -(C0-3 alkylene)-cycloalkyl, -(C0-3 alkylene)-heterocy-cloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-heteroaryl, wherein in said alkylene moiety of said -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-heteroaryl one -CH2- group if present is optionally replaced by -O-, and wherein the cycloalkyl moiety in said -(C0-3alkylene)-cycloalkyl, the heterocycloalkyl moiety in said -(C0-3alkylene)-heterocycloalkyl, the aryl moiety in said -(C0-3 alkylene)-aryl, and the heteroaryl moietyin said -(C0-3alkylene)-heteroaryl are each optionally substituted with one or more groups each independently selected from -Hal, C1-2alkyl, C1-2haloalkyl, -O(C1-2alkyl), and -O(C1-2haloalkyl); or two RS3attached to the same carbon atom form =O; or, if attached to a heterocycloalkyl ring formed by two R3together with the nitrogen atom to which they are attached, two RS3togetherwith two neighboring atoms to which they are attached form a fused heteroaryl ring; R4is absent or C1-4alkylene; R5is -Hal, -OH, C1-6alkyl, or -O(C1-6alkyl); R6is C1-6alkyl, C1-6haloalkyl, -(C1-6alkylene)-OH, -(C1-6alkylene)-O(C1-6alkyl), -(C1-6alky- lene)-N(C1-6alkyl)(C1-6alkyl), -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, or -(C0-3 alkylene)-heteroaryl, wherein in said alkylene moiety of said -(C0-3 alky-lene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-het- eroaryl one -CH2- group if present is optionally replaced by -O-, and wherein the cycloalkyl moi- ety in said -(C0-3alkylene)-cycloalkyl, the heterocycloalkyl moiety in said -(C0-3alkylene)-hetero- cycloalkyl, the aryl moiety in said -(C0-3alkylene)-aryl and the heteroaryl moiety in said -(C0-3alkylene)-heteroaryl are each optionally substituted with one or more groups each indepen-dently selected from -Hal, C1-2alkyl, C1-2haloalkyl, and -O(C1-2alkyl); X1is CH or N; X21 is CH Y o 1r N;Y is CR or N;Y2is CRY2or N; Y3is CRY3or N; Y4is CRY4or N; wherein RY1, RY2, RY3, and RY4are each independently selected from -H, -CN, -Hal, -OH, -NH2,C1-6 alkyl, C1-6 haloalkyl, -O(C1-6 alkyl), -O(C1-6 haloalkyl), and -(C1-6 alkylene)-O(C1-6 alkyl);provided that if X1and X2are both CH, at least one of Y1, Y2, Y3, and Y4is N; and provided that if X2is N, one of X1, Y1, Y2, Y3, and Y4is also N; and provided that not more than two of X1, X2, Y1, Y2, Y3, and Y4are N.2. The compound of item 1, wherein the compound of formula (I) is a compound of formula(Ia), (Ib), (Ic), (Id), (Ie), or (If) pr 3. The compound of item 1 or 2, wherein the compound of formula (I) is a compound of for-mula (Ia*), (Ib*), or (Ic*) 4. The compound of any one of items 1 to 3, wherein the compound of formula (I) is a com-pound of formula (Ia*) 5. The compound of any one of items 1 to 3, wherein the compound of formula (I) is a com-pound of formula (Ib*) 6. The compound of any one of items 1 to 3, wherein the compound of formula (I) is a com-pound of formula (Ic*) 7. The compound of any one of items 1 to 6, wherein R1 is phenyl substituted with -O(C1-6alkyl).8. The compound of any one of items 1 to 7, wherein R1 is 4-ethoxyphenyl.9. The compound of any one of items 1 to 8, wherein the moiety A isR3R2N R3,whereinR2is C2alkylene or C3alkylene.10. The compound of any one of items 1 to 9, wherein the moiety A isR3R2N R3,whereineach R3is independently selected from -H, C1-5alkyl, -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)- heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-heteroaryl, each optionally substituted with one or more RS3; wherein each RS3is independently selected from -CN, -Hal, -OH, -NH2, -NH(C1-6alkyl), -N(C1-6alkyl)(C1-6 alkyl), C1-6 alkyl, C1-6 haloalkyl, -(C1-6 alkylene)-CN, -(C1-6 alkylene)-OH, -O(C1-6 alkyl),-(C1-6alkylene)-O-(C1-6alkyl), -CO(C1-6alkyl), -CO(cycloalkyl), -CO(heterocycloalkyl), -CO-NH2, -CO-NH(C1-6alkyl), -CO-N(C1-6alkyl)(C1-6alkyl), -NH-CO(C1-6alkyl), -S(O)2-(C1-6alkyl), -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)- heteroaryl, wherein in said alkylene moiety of said -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3 alkylene)-aryl and -(C0-3 alkylene)-heteroaryl one -CH2- group if presentis optionally replaced by -O-, and wherein the cycloalkyl moiety in said -(C0-3alkylene)-cy- cloalkyl, the heterocycloalkyl moiety in said -(C0-3alkylene)-heterocycloalkyl, the aryl moiety in said -(C0-3alkylene)-aryl and the heteroaryl moiety in said -(C0-3alkylene)-heteroaryl are each optionally substituted with one or more groups each independently selected from -Hal, C1-2alkyl,C1-2 haloalkyl, and -O(C1-2 alkyl);or two RS3attached to the same carbon atom form =O.11. The compound of any one of items 1 to 9, wherein the moiety A is whereinthe two R3together with the nitrogen atom to which they are attached form a heterocycloalkyl ring, optionally substituted with one or more RS3; wherein each RS3is independently selected from -CN, -Hal, -OH, -NH2, -NH(C1-6alkyl), -N(C1-6alkyl)(C1-6alkyl), C1-6alkyl, C1-6haloalkyl, -(C1-6alkylene)-CN, -(C1-6alkylene)-OH, -O(C1-6alkyl),-(C1-6 alkylene)-O-(C1-6 alkyl), -CO(C1-6 alkyl), -CO(cycloalkyl), -CO(heterocycloalkyl), -CO-NH2,-CO-NH(C1-6alkyl), -CO-N(C1-6alkyl)(C1-6alkyl), -NH-CO(C1-6alkyl), -S(O)2-(C1-6alkyl), -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)- heteroaryl, wherein in said alkylene moiety of said -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)- heterocycloalkyl, -(C0-3alkylene)-aryl and -(C0-3alkylene)-heteroaryl one -CH2- group if presentis optionally replaced by -O-, and wherein the cycloalkyl moiety in said -(C0-3 alkylene)-cy-cloalkyl, the heterocycloalkyl moiety in said -(C0-3alkylene)-heterocycloalkyl, the aryl moiety insaid -(C0-3alkylene)-aryl and the heteroaryl moiety in said -(C0-3alkylene)-heteroaryl are each optionally substituted with one or more groups each independently selected from -Hal, C1-2alkyl, C1-2haloalkyl, and -O(C1-2S3alkyl);or two R attached to the same carbon atom form =O; or two RS3 together with two neighboringatoms to which they attached form a fused heteroaryl ring.12. The compound of any one of items 1 to 8, wherein the moiety A is

[0381] 13. The compound of any one of items 1 to 12, wherein the compound is a compound se- lected from the following compounds or a stereoisomer, tautomer, N-oxide, pharmaceutically acceptable salt or solvate thereof:

[0382] 14. A pharmaceutical composition comprising the compound of any one of items 1 to 13 and at least one pharmaceutically acceptable carrier.

[0383] 15. The compound of any one of items 1 to 13 or the pharmaceutical composition of item 14 for use as a medicament.

[0384] 16. The compound of any one of items 1 to 13 or the pharmaceutical composition of item 14 for use in the treatment or prevention of an autoimmune disorder or inflammatory condition.

[0385] 17. The compound for use or the pharmaceutical composition for use of item 16, wherein the autoimmune disorder is selected from systemic lupus erythematosus, rheumatoid arthritis, scle- roderma, Sjogren’s syndrome, polymyositis / dermatomyositis, primary biliary cirrhosis, multiple sclerosis, oral ulcers, periodontitis, Behget’s disease, myasthenia gravis, and ankylosing spondylitis, preferably wherein the autoimmune disorder is systemic lupus erythematosus, or wherein the inflammatory condition is selected from inflammatory bowel disease, psoriasiform dermatitis, endosomal TLR-dependent inflammation, ulcerative colitis, Crohn’s disease, endoso- mal TLR-induced hyperinflammation, macrophage activation syndrome, allergic airway inflam- mation, and sarcoidosis, preferably wherein the inflammatory condition is selected from inflam- matory bowel disease, psoriasiform dermatitis, and endosomal TLR-dependent inflammation.

[0386] 18. The compound for use or the pharmaceutical composition for use of item 16 or 17, wherein the autoimmune disorder is a disorder associated with SLC15 peptide transporter, and / or wherein said compound or said pharmaceutical composition inhibits SLC15 peptide transporter.

Claims

Claims1. A compound of formula (I)or a stereoisomer, tautomer, N-oxide, pharmaceutically acceptable salt or solvate thereof, wherein:R1 is phenyl substituted with one or more RS1;wherein each RS1is independently selected from -Hal, C1-6alkyl, C1-6haloalkyl, -cycloalkyl, -O(C1-6alkyl), -O(C1-6haloalkyl), and -NH-CO(C1-6alkyl); or two RS1together form a fused hete- rocycloalkyl or heteroaryl moiety;A is a moiety selected fromwherein the wavy line in each case marks the connection to the remainder of the molecule; and wherein: R2is C2-4alkylene or C6cycloalkylene, each optionally substituted with one or more RS2; wherein each RS2is independently selected from -OH, -F, and -CH3; or two RS2together form =O; each R3is independently selected from -H, C1-5alkyl, -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3 alkylene)-aryl, and -(C0-3 alkylene)-heteroaryl, each optionally substitutedwith one or more RS3; provided that not both R3are -H; or the two R3together with the nitrogen atom to which they are attached form a heterocycloalkyl ring, optionally substituted with one or more RS3; wherein each RS3is independently selected from -CN, -Hal, -OH, -NH2, -NH(C1-6alkyl), -N(C1-6alkyl)(C1-6 alkyl), C1-6 alkyl, C1-6 haloalkyl, -(C1-6 alkylene)-CN, -(C1-6 alkylene)-OH, -(C1-6 alky-lene)-NH(C1-6alkyl), -(C1-6alkylene)-N(C1-6alkyl)(C1-6alkyl), -O(C1-6alkyl), -O(C1-6haloalkyl), -(C1-6alkylene)-O(C1-6alkyl), -S(C1-6alkyl), -S(C1-6haloalkyl), -(C1-6alkylene)-S(C1-6alkyl), -COH, -CO(C1-6alkyl), -CO(cycloalkyl), -CO(heterocycloalkyl), -COOH, -COO(C1-6alkyl), -CO-NH2, -CO-NH(C1-6alkyl), -CO-N(C1-6alkyl)(C1-6alkyl), -NH-CO(C1-6alkyl), -N(C1-6alkyl)-CO(C1-6alkyl),-S(O)2-(C1-6 alkyl), -S(O)2-NH2, -S(O)2-NH(C1-6 alkyl), -S(O)2-N(C1-6 alkyl)(C1-6 alkyl), -NH-S(O)2-(C1-6alkyl), -N(C1-6alkyl)-S(O)2-(C1-6alkyl), -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocy- cloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-heteroaryl, wherein in said alkylene moiety of said -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-heteroaryl one -CH2- group if present is optionally replaced by -O-, and wherein thecycloalkyl moiety in said -(C0-3 alkylene)-cycloalkyl, the heterocycloalkyl moiety in said -(C0-3alkylene)-heterocycloalkyl, the aryl moiety in said -(C0-3alkylene)-aryl, and the heteroaryl moiety in said -(C0-3alkylene)-heteroaryl are each optionally substituted with one or more groups each independently selected from -Hal, C1-2alkyl, C1-2haloalkyl, -O(C1-2alkyl), and -O(C1-2haloalkyl); or two RS3attach 3ed to the same carbon atom form =O; or, if attached to a heterocyc Sl 3oalkyl ringformed by two R together with the nitrogen atom to which they are attached, two R togetherwith two neighboring atoms to which they are attached form a fused heteroaryl ring;R4is absent or C1-4alkylene; R5is -H, -Hal, -OH, C1-6alkyl, or -O(C1-6alkyl); R6is C1-6alkyl, C1-6haloalkyl, -(C1-6alkylene)-OH, -(C1-6alkylene)-O(C1-6alkyl), -(C1-6alky-lene)-N(C1-6 alkyl)(C1-6 alkyl), -(C0-3 alkylene)-cycloalkyl, -(C0-3 alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, or -(C0-3alkylene)-heteroaryl, wherein in said alkylene moiety of said -(C0-3alky- lene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-het- eroaryl one -CH2- group if present is optionally replaced by -O-, and wherein the cycloalkyl moi- ety in said -(C0-3alkylene)-cycloalkyl, the heterocycloalkyl moiety in said -(C0-3alkylene)-hetero-cycloalkyl, the aryl moiety in said -(C0-3 alkylene)-aryl and the heteroaryl moiety in said -(C0-3alkylene)-heteroaryl are each optionally substituted with one or more groups each indepen- dently selected from -Hal, C1-2alkyl, C1-2haloalkyl, and -O(C1-2alkyl); X1is CH or N;X2 is CH or N;Y1is CRY1or N; Y2is CRY2or N; Y3is CRY3or N; Y4is CRY4wherein RY1o ,RYr 2 N; ,RY3, and RY4 are each independently selected from -H, -CN, -Hal, -OH, -NH2,C1-6alkyl, C1-6haloalkyl, -O(C1-6alkyl), -O(C1-6haloalkyl), and -(C1-6alkylene)-O(C1-6alkyl); provided that if X1and X2are both CH, at least one of Y1, Y2, Y3, and Y4is N; and provided that if X2is N, one of X1, Y1, Y2, Y3, and Y4is also N; and provided that not more than two of X1, X2, Y1, Y2, Y3, and Y4are N.

2. The compound of claim 1, wherein RY1, RY2, RY3, and RY4 are each independently selectedfrom -H, -CN, -Hal, -OH, C1-6alkyl, C1-6haloalkyl, -O(C1-6alkyl), -O(C1-6haloalkyl), and -(C1-6alkylene)-O(C1-6alkyl).

3. The compound of claim 1 or 2, wherein the compound of formula (I) is a compound of for-mula (Ia), (Ib), (Ic), (Id), (Ie), or (If)pr4. The compound of any one of claims 1 to 3, wherein the compound of formula (I) is a com- p5. The compound of any one of claims 1 to 4, wherein the compound of formula (I) is a com- pound of formula (la), (lb), (Ic), (Id), or (le)wherein RY1, RY2, RY3, and RY4are each independently selected from -H, -CN, -Hal, -OH, C1-6alkyl, C1-6haloalkyl, -O(C1-6alkyl), -O(C1-6haloalkyl), and -(C1-6alkylene)-O(C1-6alkyl).

6. The compound of any one of claims 1 to 5, wherein the compound of formula (I) is a com-7. The compound of any one of claims 1 to 6, wherein the compound of formula (I) is a com-pound of formula (Ia*), (Ib*), or (Ic*)8. The compound of any one of claims 1 to 7, wherein the compound of formula (I) is a com-pound of formula (Ia*)9. The compound of any one of claims 1 to 7, wherein the compound of formula (I) is a com-pound of formula (Ib*)10. The compound of any one of claims 1 to 7, wherein the compound of formula (I) is a com-pound of formula (Ic*)11. The compound of any one of claims 1 to 10, wherein R1 is phenyl substituted with-O(C1-6alkyl).

12. The compound of any one of claims 1 to 11, wherein R1 is 4-ethoxyphenyl.

13. The compound of any one of claims 1 to 12, wherein the moiety A iswhereinR2 is C2 alkylene or C3 alkylene.

14. The compound of any one of claims 1 to 13, wherein the moiety A iswhereineach R3 is independently selected from -H, C1-5 alkyl, -(C0-3 alkylene)-cycloalkyl, -(C0-3 alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-heteroaryl, each optionally substituted with one or more RS3; wherein each RS3is independently selected from -CN, -Hal, -OH, -NH2, -NH(C1-6alkyl), -N(C1-6alkyl)(C1-6alkyl), C1-6alkyl, C1-6haloalkyl, -(C1-6alkylene)-CN, -(C1-6alkylene)-OH, -O(C1-6alkyl),-(C1-6 alkylene)-O-(C1-6 alkyl), -CO(C1-6 alkyl), -CO(cycloalkyl), -CO(heterocycloalkyl), -CO-NH2,-CO-NH(C1-6alkyl), -CO-N(C1-6alkyl)(C1-6alkyl), -NH-CO(C1-6alkyl), -S(O)2-(C1-6alkyl), -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)- heteroaryl, wherein in said alkylene moiety of said -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)- heterocycloalkyl, -(C0-3alkylene)-aryl and -(C0-3alkylene)-heteroaryl one -CH2- group if presentis optionally replaced by -O-, and wherein the cycloalkyl moiety in said -(C0-3 alkylene)-cy-cloalkyl, the heterocycloalkyl moiety in said -(C0-3alkylene)-heterocycloalkyl, the aryl moiety in said -(C0-3alkylene)-aryl and the heteroaryl moiety in said -(C0-3alkylene)-heteroaryl are each optionally substituted with one or more groups each independently selected from -Hal, C1-2alkyl, C1-2haloalkyl, and -O(C1-2alkyl);or two RS3 attached to the same carbon atom form =O.

15. The compound of any one of claims 1 to 13, wherein the moiety A iswherein the two R3together with the nitrogen atom to which they are attached form a heterocycloalkyl ring, optionally sS3Su 3bstituted with one or more R ;wherein each R is independently selected from -CN, -Hal, -OH, -NH2, -NH(C1-6 alkyl), -N(C1-6alkyl)(C1-6alkyl), C1-6alkyl, C1-6haloalkyl, -(C1-6alkylene)-CN, -(C1-6alkylene)-OH, -O(C1-6alkyl), -(C1-6alkylene)-O-(C1-6alkyl), -CO(C1-6alkyl), -CO(cycloalkyl), -CO(heterocycloalkyl), -CO-NH2, -CO-NH(C1-6alkyl), -CO-N(C1-6alkyl)(C1-6alkyl), -NH-CO(C1-6alkyl), -S(O)2-(C1-6alkyl), -(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl, and -(C0-3alkylene)-heteroaryl, wherein in said alkylene moiety of said -(C0-3 alkylene)-cycloalkyl, -(C0-3 alkylene)-heterocycloalkyl, -(C0-3alkylene)-aryl and -(C0-3alkylene)-heteroaryl one -CH2- group if present is optionally replaced by -O-, and wherein the cycloalkyl moiety in said -(C0-3alkylene)-cy- cloalkyl, the heterocycloalkyl moiety in said -(C0-3alkylene)-heterocycloalkyl, the aryl moiety in said -(C0-3alkylene)-aryl and the heteroaryl moiety in said -(C0-3alkylene)-heteroaryl are eachoptionally substituted with one or more groups each independently selected from -Hal, C1-2 alkyl,C1-2haloalkyl, and -O(C1-2alkyl); or two RS3attached to the same carbon atom form =O; or two RS3together with two neighboring atoms to which they attached form a fused heteroaryl ring.

16. The compound of any one of claims 1 to 12, wherein the moiety A is.

17. The compound of any one of claims 1 to 16, wherein the compound is a compound se-lected from the following compounds or a stereoisomer, tautomer, N-oxide, pharmaceuticallyacceptable salt or solvate thereof:,18. The compound of any one of claims 1 to 16, wherein the compound is a compound se- lected from the following compounds or a stereoisomer, tautomer, N-oxide, pharmaceutically acceptable salt or solvate thereof:

19. The compound of any one of claims 1 to 16, wherein the compound is a compound se- lected from the following compounds or a stereoisomer, tautomer, N-oxide, pharmaceutically acceptable salt or solvate thereof:

20. A pharmaceutical composition comprising the compound of any one of claims 1 to 19 and at least one pharmaceutically acceptable carrier.

21. The compound of any one of claims 1 to 19 or the pharmaceutical composition of claim 20 for use as a medicament.

22. The compound of any one of claims 1 to 19 or the pharmaceutical composition of claim 20 for use in the treatment or prevention of an autoimmune disorder or inflammatory condition.

23. The compound for use or the pharmaceutical composition for use of claim 22, wherein the autoimmune disorder is selected from systemic lupus erythematosus, rheumatoid arthritis, scle- roderma, Sjogren’s syndrome, polymyositis / dermatomyositis, primary biliary cirrhosis, multiple sclerosis, oral ulcers, periodontitis, Behget’s disease, myasthenia gravis, and ankylosing spondylitis, preferably wherein the autoimmune disorder is systemic lupus erythematosus, or wherein the inflammatory condition is selected from inflammatory bowel disease, psoriasiform dermatitis, endosomal TLR-dependent inflammation, ulcerative colitis, Crohn’s disease, endoso- mal TLR-induced hyperinflammation, macrophage activation syndrome, allergic airway inflam- mation, and sarcoidosis, preferably wherein the inflammatory condition is selected from inflam- matory bowel disease, psoriasiform dermatitis, and endosomal TLR-dependent inflammation.

24. The compound for use or the pharmaceutical composition for use of any of claims 21 to 23, wherein the autoimmune disorder is a disorder associated with SLC15 peptide transporter, and / or wherein said compound or said pharmaceutical composition inhibits SLC15 peptide transporter-TASL assembly.

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