PYRIDIN-3-YL DERIVATIVES AS 1MMUNOMODULAT1NG AGENTS Field of the invention The present invention relates to S1P1/EDG1 receptor agonists of Formula (1) and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing a compound of the Formula (I), and their use as compounds improving vascular function and as immunomodulating agents, either alone or in combination with other active compounds or therapies. A further aspect of the invention relates to novel compounds of Formula {11} that serve as intermediates to prepare compounds of Formula (I). Background of the invention The human immune system is designed to defend the body against foreign micro¬organisms and substances that cause infection or disease. Complex regulatory mechanisms ensure that the immune response is targeted against the intruding substance or organism and not against the host. In some cases, these control mechanisms are unregulated and autoimmune responses can develop. A consequence of the uncontrolled inflammatory response is severe organ, cell, tissue or Joint damage. With current treatment, the whole immune system is usually suppressed and the body's ability to react to infections is also severely compromised. Typical drugs in this class include azathiophne, chlorambucil, cyclophosphamide, cyclosporin, or methotrexate. Corticosteroids which reduce inflammation and suppress the immune response, may cause side effects when used in long term treatment. Nonsteroidal anti-infammatory drugs (NSAIDs) can reduce pain and inflammation, however, they exhibit considerable side effects. Alternative treatments include agents that activate or block cytokine signaling. Orally active compounds with immunomodulating properties, without compromising immune responses and with reduced side effects would significantly improve current treatments of uncontrolled inflammatory disease. In the field of organ transplantation the host immune response must be suppressed to prevent organ rejection. Organ transplant recipients can experience some rejection even when they are taking immunosuppressive drugs. Rejection occurs most frequently in the first few weeks after transplantation, but rejection episodes can also happen months or even years after transplantation. CoiribinaiJons of ux^ to m.-Be or Kxjr medications are commonly used to give maximum proiecbor agairsi ^^eczo- *~;ie rrurdmizir'g side effects. Current standard drugs used to treat the rejection of transplanied organs interfere with discrete intracellular pathways in the activation of T-type or B-type white blood celis-Examples of such drugs are cyclosporin, daclizumab, basiliximab, everolimus, or FK506, which interfere with cytokine release or signaling; azathioprine or lefiunomide, which inhibit nucleotide synthesis; or 15-deoxyspergualin. an inhibitor of leukocyte differentiation. The beneficial effects of broad immunosuppressive therapies relate to their effects; however, the generalized immunosuppression which these drugs produce diminishes the immune system's defense against infection and malignancies. Furthermore, standard immunosuppressive drugs are often used at high dosages and can cause or accelerate organ damage. Description of the invention The present invention provides novel compounds of Formula {I) that are agonists for the G protein-coupled receptor S1P1/EDG1 and have a powerful and long-lasting immunomodulating effect which is achieved by reducing the number of circulating and infiltrating T- and B-lymphocytes, without affecting their maturation, memory, or expansion. The reduction of circulating T- / B-lymphocytes as a result of S1P1/EDG1 agonism, possibly in combination with the observed improvement of endothelial cell layer function associated with S1P1/EDG1 activation, makes such compounds useful to treat uncontrolled inflammatory disease and to improve vascular functionality. The compounds of the present invention can be utilized alone or in combination with standard drugs inhibiting T-cell activation, to provide a new immunomodulating therapy with a reduced propensity for infections when compared to standard immunosuppressive therapy. Furthermore, the compounds of the present invention can be used in combination with reduced dosages of traditional immunosuppressant therapies, to provide on the one hand effective immunomodulating activity, while on the other hand reducing end organ damage associated with higher doses of standard immunosuppressive drugs. The observation of improved endothelial cell layer function associated with S1P1/EDG1 activation provides additional benefits of compounds to improve vascular function. The nucleotide sequence and the amino acid sequence for the human S1P1/EDG1 receptor are known in the art and are published in e.g.: Hla, T.. and Maciag, T. J. Biol Chem. 265 (19901. 9308-9313: WO 31/155c3 --ubiished 17 Odober 19S1; WO 99/46277 c-ublished 16 September 1999. The potsncy anc efficsr. -" ~~~ zorxDOunas of Formula (ii are assessed using a GTPyS assay to deterrnine EC5; values and by measuring the circulating lymphocytes in the rat after oral administration, respectively (see In Examples). The general terms used hereinbefore and hereinafter preferably have, within this disclosure, the following meanings, unless otherwise indicated; Where the pluraf form is used for compounds, salts, pharmaceutical compositions, diseases and the like, this is intended to mean also a single compound, salt, or the like. Any reference hereinbefore or hereinafter to a compound of Formula (I) is to be understood as referring also to salts, especially pharmaceutically acceptable salts, of a compound of Formula (I), as appropriate and expedient. The term Ci^-alkyl alone or in combination with other groups, means saturated, branched or straight chain groups with one to five carbon atoms. Examples of Ci.5-alkyl groups are methyl, ethyl, n-propyl, /so-propyl, n-butyl, /so-butyl, n-pentyl, and /so-pentyl. Likewise, the term Ci-4-alky!, alone or in combination with other groups, means saturated, branched or straight chain groups with one to four carbon atoms. Examples of Ci.4-alkyl youps are methyl, ethyl, n-propyl, /so-propyl, n-butyl, and /so-butyl. Likewise, the term Ci.3-alkyl, alone or in combination with other groups, means saturated, branched or straight chain groups with one to three cartmn atoms and represents a methyl, ethyl, n-propyl, or /so-propyl group; preferred are methyl and ethyl. Likewise, the term C2-s-alkyl, alone or in combination with other groups, means saturated, branched or straight chain groups with two to five carbon atoms. Likewise, the term Cz^-alkyl, alone or in combination with other groups, means saturated, branched or straight chain groups with two to four carbon atoms. Examples of C^^-alkyl groups are ethyl, n-propyl, /so-propyl, n-butyl, and /so-butyl. The term Cu-alkoxy. alone or in combinaijofi wrtr DTT^ST gro-jps. rrisans an R-0 group, wherein R is a C-^-alkyl. Examples o"' C-^-aDt-Xv grc-v^Cs =.-= T.encx>'. euicxy, propoxy. /so-propoxy, and /so-butoxy, preferred are methoxy, etboxy, propoxy. and /so-propoxy. The term C2-5-alkoxy, alone or in combination with other groups, means an R-0 group, wherein R is a C2.5-alkyl. Examples of C2.5-alkoxy groups are ethoxy, propoxy, /so-propoxy, /so-butoxy, and /so-pentoxy. The term halogen means fluoro, chloro, bromo or iodo, preferably fluoro or chloro, most preferably chloro. Salts are preferably the pharmaceutically acceptable salts of the compounds of Formula (I). The term "pharmaceutically acceptable salts" refers to non-toxic, inorganic or organic acid and/or base addition salts, Lit. e.g. "Salt selection for basic drugs", Int. J. Pharm. (1986), 33,201-217. The compounds of Formula (I) may contain one or more stereogenic or asymmetric centers, such as one or more asymmetric carbon atoms. Substituents at a double bond or a ring may be present in cis- {= Z-) or trans (= E-) form unless indicated otherwise. The compounds of Formula (I) may thus be present as mixtures of stereoisomers or preferably as pure stereoisomers. Mixtures of stereoisomers may be separated in a manner known to a person skilled in the art. i) The invention relates to pyridin-3-yl derivatives of the Formula (I), Formula (I) wherein A represents *-CONH-CH2-, '-CO-CH=CH-, *-CO-CH2CH2-, ,o. \\ J w 'I 0~H N—d N—N N—H or wherein the asterisks indicate the bond that is linked to the pyridine group of Formula (1); R' represents hydrogen, Ci^-a(ky[, or chloro; R^ represents C,.5-alkyl or CM-alkoxy; R^ represents hydrogen, C-i^-alkyl, Ci-4-alkoxy, or halogen; R^ represents hydrogen, Cu-alkyl, Ci^-alkoxy, halogen, \n^\uoxoxne\hy\ or trifluoromethoxy; R^ represents 2,3-dihydroxy propyl, dKhydroxy-Cn-alkyl)-Ci^-alkyi, -CH2-(CH3X-NHSO2R", -{CH2)„CH(OH)-CH2-NHS02R^. -CHHCHJVNHCOR^, -{CH2)„CH(0H)-CH^^ NHCOR", -CH2-(CH2}n-CONR^'R", -CO-NHR^\ H3-carboxy-azetidiny()-2-acetyl, 1-(2-carboxy-pyn"olidinyl)-2-acetyl, 1-(3-cgrt)oxy-pyrTOlidinyl)-2-acetyl, 1-tS-cartwxy-azetidinyl)-3-propionyl, 1-(2-carboxy-pyrrolidinyt)-3-propionyl, 1-{3-cart)Oxy-pyrTolidinyl)-3-propionyl, -(CH2)nCH{OH)-CH2-NR^^R^, hydroxy. hydroxy-Cz.s-alkoxy, di-(hydroxy-CM-alkyl)-CM-alkoxy, 2,3-dihydroxy-propoxy, 2-hydroxy-3-methoxy-propoxy, -OCH2-(CH2)m-NR^'R^^, 2-[(azetidine-3-carboxylic acid)-1-yl]-ethoxy, 2-[(azetidine-3-carboxylic add Ci,5-alkylester)-1-yl]-ethoxy, 2-[(pyrrolid;ne-3-carboxyl(c acid)-1-yII-ethoxy, 2-[(pyrTolidine-3-carboxylic acid Ci.5-alkylester)-1-yl]-ethoxy, -OCHz-CH(OH)-CHrNR^'R^, 3-[(azetidine-3-carboxy(ic acid)-1 -yl]-2-hydroxypropoxy, 3-[{azetidine-3-carboxylic acid Ci-5-alkylester)-1 -yl]'2-hydroxypropoxy, 2-hydroxy-3-{(pyrro)idine-3-carboxylic acid)-1-yl]-propoxy, 2-hydroxy-3-[{pyrro(idine-3-carboxy(ic acid Ci-5-aIkylester)-1-y(]-propoxy, 2-hydroxy-3-[(pyrrol(dine-2-carboxylic acid)-1-yl]-propoxy, 2-hydroxy-3-[{pyrrolidine-2-carboxyIic acid Ci.5-alkylester)-1- yil-propoxy. -OCHj-fCHsWNHSO^R-. ^3CH2-CH;Cr:,~Dhz-NH302R", OCH;-{CH;>-NHCOR^. -OCH2-CH(OHVCH;-NHCOR^: R^^ represents hydrogen, C,_3-alkyl, 2-hydroxyethy[. 2-hydroxy-1-hydroxymethyl-ethyl, 2,3-dihydroxypropyl, carboxymethyl, 1-(Ci-5-alkylcarboxy)methy!, 2-carboxyethyl, or 2-(Ci_5-alkylcarboxy)ethyI; R" represents hydrogen, methyl, or ethyl; R" represents Ci-3-alkyl, methylamino, ethylamino, ordimethylamino; R" represents hydroxymethyl, hydroxyethyl, aminomethyl, methylaminomethyl, dimethylaminomethyl, aminoethyl, 2-methylamino-ethyl, or2-dimethy!amino-ethyl; k represents the integer 1, 2, or 3; m represents the integer 1 or 2; n represents 0, 1, or 2; and R* represents hydrogen, C^-alkyl or halogen. ii) Another embodiment of the invention relates to pyridin-3-yi derivatives according to embodiment i), wherein A represents O—N N—O N—N N N ^^^ N N—/ .0, * n or , / -N N wherein the asterisks indicate the bond that is linked to the pyridine group of Formula (I). iii''. -Another emtxKfiment of the invention rBtates re c^ridL-i-cr-v-i derrv3ttv=s according to er-;bodin"ient i), wherein A represents O N N—O N N or N N \^ N wherein the asterisks indicate the bond that is linked to the pyridine group of Formula (I). iv) Another embodiment of the invention relates to pyridin-3-yl derivatives according to embodiment i), wherein A represents 'Yr- '-""' "-< Y < II O N , N—O , or N N ) w/herein the asterisks indicate the bond that is linked to the pyridine group of Fonnula (I). v) Another embodiment of the invention relates to pyridin-3-yl derivatives according to embodiment i), wherein A represents O N N—d wherein the asterisks indicate the bond that is linked to the pyridine group of Formula {I). vi'! Another smbodimsnt of the invention rBtsies tc pyrrdin-S-/; derrvattvss according to er-ibodiment \). wherein A represents 6—N wherein the asterisk indicates the bond that is linked to the pyridine group of Formula (I). vii) Another embodiment of the invention relates to pyridin-3-yl derivatives according to embodiment i), wherein A represents N N viii) Another embodiment of the invention relates to pyridin-3-yl derivatives according to any one of the embodiments i) to vii), wherein R'' represents Ci_4-alkyt or chloro. ix) Another embodiment of the invention relates to pyridin-3-yl derivatives according to any one of the embodiments i) to vii), wherein R"* represents Ci-^-alkyl. x) Another embodiment of the invention relates to pyridin-3-yl derivatives according to any one of the embodiments i) to vi), wherein R^ represents methyl or ethyl. xi) Another embodiment of the invention relates to pyridin-3-yl derivatives according to any one of the embodiments i) to vi), wherein R'' represents methyl. xii) Another embodiment of the invention relates to pyridin-3-yl derivatives according to any one of the embodiments i) to xi), wherein R^ represents Ci.s-alkyi. xiii) Another embodiment of the invention relates to pyridin-3-yl derivatives according to any one of the embodiments i) to xi), wherein R^ represents C^-A-alkyl. xfv) Another embodiment of the invention relates to pyridin-3-yl derivatives according to any one of the embodiments i) to xi), wherein R^ represents ethyl, n-propyl, /so-propyl, or iso-butyl. xv'^ Another embodiment of the invention relates ID pyndtri-o-yi aerjv3trves according to any or^ of the embodiments i) to xi). wherein R^ -^oresants '-zrxry' 3' 'sc-buiy'^. xvi) Another embodiment of the invention relates to pyridin-3-yi derivatives according to any one of the embodiments i) to xi), w/herein R^ represents Cij-afkoxy. xvii) Another embodiment of the invention relates to pyridin-3-yl derivatives according to any one of the embodiments i) to xvi). wherein at least one of R', R"* and R^ represents a group other than hydrogen, xviii) Another embodiment of the invention relates to pyridin-3-yl derivatives according to any one of the embodiments i) to xvi), vi'herein R' represents methyl or methoxy (especially methoxy), and R* and R^ represent hydrogen. xix) Another embodiment of the invention relates to pyridin-3-yl derivatives according to any one of the embodiments i) to xvi), wherein R' represents hydrogen. xx) Another embodiment of the invention relates to pyridin-3-yl derivatives according to any one of the embodiments i) to xvi), wherein R^ represents hydrogen; and R^ represents CM-alkyl, or d^-alkoxy; and R^ represents Ci^-alkyl, or halogen. xxi) Another embodiment of the invention relates to pyridin-3-yl derivatives according to any one of the embodiments i) to xvi), vi/herein R^ represents hydrogen, R* represents C1-3-alkyl, or methoxy (especially methyl, ethyl, or methoxy), and R^ represents methyl, ethyl, or halogen (especially chloro). xxii) Another embodiment of the invention relates to pyridin-3-yl derivatives according to any one of the embodiments i) to xvi), wherein R^ represents hydrogen, and K* and R* represent a methyl group. xxiii) Another embodiment of the invention relates to pyridin-3-yl derivatives according to any one of the embodiments i) to xvi), wherein R' represents iiydrogen, R^ represents a methyl group, and R^ represents an ethyl group. xxj-y'i Another embodiment of the invention T&^BS TO pyridir-3-y^ dertvativss 3ccx)rding to any one of the embodiments i) to xvi). 'f^^-^r R^ '^L'^^^^-^ -yarDgsn. R* reoresents a methoxy group, and R^ represents chloro. xxv) Another embodiment of the invention relates to pyridin-3-yl derivatives according to any one of the embodiments i) to xvi), wherein R^ represents hydrogen, R* represents a methyl group, and R^ represents chloro. xxvi) Another embodiment of the invention relates to pyndin-3-yl derivatives according to any one of the embodiments i) to xxv), wherein R^ represents 2,3-dihydroxypropyl, di-(hydroxy-CM-alkyl)-Ci^-alkyl, -CH2-(CH2)k-NHSO^R'^ -(CH2)nCH(OH)-CH2-NHS02R", -CHHCH2)rNHC0R^, -(CHj),CH(0H)-CH2-NHC0R^, -CH2-(CH^)n-C0NR^'R^^ -CO-NHR^\ -{CH2)nCH(OH)-CH2-NR^^R^^ hydroxy. hydroxy-C^.s-alkoxy, di-(hydroxy-C,^-alkyi)-C,^-alkoxy, 2,3-dihydroxy-propoxy, 2-hydroxy-3-methoxy-propoxy, -OCH2-{CH2)m-NR^'R^^, -OCH3-CH(OH)-CH2-NR^^R^^ -0CH2-(CH2)^-NHS02R", -OCH2-CH(OH}-CH2-NHSOaR", -OCH2-(CH2)rn-NHCOR^, or -OCHs-CHfOH^CH^-NHCOR". xxvii) Another embodiment of the invention relates to pyridin-3-yI derivatives according to any one of the embodiments i) to xxv), vi/herein R* represents 2,3-dihydroxypropyl, -CH2- (CH2)k-NR=^R^^ -CH2-(CH2)^-NHCOR^, -(CH2)nCH(OH)-CH2-NHCOR^, -CH2-{CH2)n- CONR^^R", -CO-NHR^', -{CH2)nCH(OH)-CH2-NR^^R^, hydroxy-Cz.s-alkoxy, di-{hydroxy-Ci- 4-akyl)-Ci-,-alkoxy, 2,3-dihydroxy-propoxy, 2-hydroxy-3-methoxy-propoxy, -OCH2-(CH2)m- NR51R52 -0CH^-CH(0H)-CH2-NR^'R^^ -OCH2-(CH2)„-NHCOR^, or -0CHz-CH(0H)-CH2- NHCOR^ {especially R^ represents 2,3-dihydroxypropyl, -CH2-{CH2)k-NR^'R", -CH2- (CH2),-NHC0R^, -(CH2)nCH{OH)-GH2-NHCOR", -CH2-{CH^),-C0NR^^R^^ -(CH2)nCH(OH)-CH2-NR^^R^, hydroxy-Ca-s-aikoxy, di-(hydroxy-C,^-alkyl)-Cn-alkoxy, 2,3-dihydroxy-propoxy, 2-hydroxy-3-methoxy-propoxy, -OCHj-fCHjlm-NR^^R", -OCH2-CH(OH)-CH2-NR^'R", -OCH2-(CH2)m-NHCOR^, or -OCH2-CH(OH)-CH2-NHCOR"). xxviii) Another embodiment of the invention relates to pyridin-3-yl derivatives according to any one of the embodiments i) to xxv), vi^herein R^ represents hydroxy-C2_5-alkoxy, di- (hydroxy-Ci^-alkyl)-Ci^-alkoxy, 2,3-dihydroxy-propoxy, -OCH2-(CH2)^-NR^^R^^ -OCH2-CH(OH)-CH2-NR^^R^^ -OCH2-(CH2)r,-NHCOR", or -OCH2-CH(OH)-CH2-NHCOR^. xxix) Another embodiment of the invention relates to pyridin-3-yl derivatives according to any one of the embodiments i) to xxv), wherein R* represents 3-hydroxy-2-hydroxymethyl- propoxy. 2.3-dihydrDxy-propoxy. or -OCh~Cn(OHrCHz-NhCOR^ (especially R^ represents 2,3-dihydroxy-propoxy or -OOHr-'C-—C—-D---t-NHCOR^ A+>erein R^ represents hydroxymethy)). xxx) Another embodiment of the invention relates to pyridin-S-y! derivatives according to any one of the embodiments i) to xxv), vt/herein R* represents -OCH2-CH(OH)-CH2-NHCOR^, wherein R" represents hydroxymethyl. xxxf) Another embodiment of the invention relates to pyridin-3-yl derivatives according to any one of the embodiments i) to xxv), wherein R* represents 2,3-dihydroxy-propoxy. xxxii) Another embodiment of the invention relates to pyridin-3-yl derivatives according to embodiment i), wherein A represents N N , or (especially A represents -N. , or N N ) wherein the asterisks indicate the bond that is linked to the pyridine group of Formula {I); R'' represents methyl, ethyl, or chloro (especially methyl, or ethyl); R^ represents n-propyl, isobutyl, or isopropoxy (especially n-propy) or isobutyl); R^ represents hydrogen, methyl, or methoxy (especially hydrogen or methoxy); R* represents hydrogen, methyl, ethyl or methoxy; R^ represents hydroxy-Cs-s-alkoxy, di-(hydroxy-Ci^-alkyl)-Ci^-alkoxy, 2,3-dihydroxy-propoxy, -OCH2-CH(OH)-CH?-NR^'R^^ or -0CH2-CH(0H)-CHj-NHC0R^ (especially R* represents 2,3-dihydroxy-propoxy, or -OCH2-CH(OH)-CH2-NHCOR^); R" represents hydroxymethyl, methylaminomethyt, or 2-methylamino-ethyl; and R* represents hydrogen, methyl, ethyl or chloro; wherein for the present embodiment the meanings of one or rr.ors of the Su-bstituents or groups may be replaced by the meanirigj^s; orvsr TD^ 3a*c s-ji^s-i^ent's) or arouo'sl in any one of embodiments v) to vii), x), xi), xv), xvii) to xix), xxii) to xxv), and xxix) to xxxi). xxxiii) Another embodiment of the invention relates to pyridin-3-yl derivatives according to embodiment i), wherein A represents . or {especially A represents -N. , or N N ), wherein the asterisl3-{2-Ethyl^-[5-(6-isobutyl-5-methyl-pyridin-3-ylH1,2,4]oxadiazoU3-yl]-6-methyl- phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide; (R)-3-{4-[5-(5,6-Diisobutyl-pyridin-3-yl)-[1,2,4loxadiazol-3-yll-2.6-dimethyl-phenoxy}- propane-1,2-diol; (S)-3-{4-[5-(5,6-Diisobuty(-pyridin-3-yl)-[1,2,4]oxadrazo(-3-y(]-2,6-d(methy(-phenoxy}- propane-1.2-diol; N^fRV3-{445-(5,5-Diethyt-pyridin-3'yl)-[1.2.4]GX3diazoi-3^/i]-2-einyi-6-rietby^?^^ h ydrcx-y-prapyl )-2-hyd roxy-acetam ide; N-((S)-3-{4-[5-(5,6-Diethyl-pyridin-3-ylHl,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide; 2-Hydroxy-N-((R)-2-hydroxy-3-{4-[5-(6-isobutyl-5-methyl-pyridin-3-ylHr2,4)oxadiazol-3-yl]-3-m6thyl-phenoxy}-propyi)-acetamide; 2-Hydroxy-N-((S)-2-hydroxy-3-{4-[5-(6-isobutyl-5-methy!-pyridin-3-yl}-[1,2,4]oxadJazol-3-yl]-3-methyl-phenoxy}-propyO-acetamide; N-({R}-3-{2-Chloro-4-[5-(6-isobutyl-5-methyl-pyridin-3-yl)-[1,2,4joxadiazol-3-yl]-6-methyl- phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide; N-((S)-3-{2-Chloro-4-[5-(6-isobutyl-5-methyl-pyridin-3-ylH1,2,4]oxadiazol~3-yl]-6-methyl- phenoxy}-2-hy d roxy-p ro py I )-2-h yd roxy-aceta m ide; N-((R)-3-{2-Chloro-4-[5-(6-isobuty!-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-6-methoxy- phenoxy}-2-hydroxy-propy I )-2-h yd roxy-aceta m ide; N-((S)-3-{2-Chloro-4-[5-(6-isobutyl-5-methyl-pyridin-3-yl)-(1,2,4]oxadiazol-3-yl]-6-methoxy- phenoxy}-2-hyd roxy-p ropy I )-2-h yd roxy-acetamide; N-((R)-3-{2-Ethyl-4-[5-(6-isobutyl-5-methyl-pyridin-3-ylH1,2.4]oxadiazo!-3-y[]-6-methyl- phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide; N-{(S)-3-{2-Ethyl-4-[3-(6-isobutyl-5-methyl-pyridin-3-ylH1,2,4]oxadiazol-5-yl]-6-methyl- phenoxy}-2-hyd roxy-p ropyl)-2-hyd roxy-acetamide; N-((S)-3-[2-Ethyi-4-[5-(6-isobutyl-pyridin-3-ylH1.2.4]oxadiazol-3-yl]-6-methyl-phenoxy}-2- hydroxy-p ropy l)-2-hyd roxy-acetamide; (S)-3-{2-Etliy!-4-[5-(5-ethyl-6-isobutyl-pyridin-3-ylH1-2.4]oxadiazo!-3-y!]^-methyl-phenoxy)^ propane-1,2-diol; N-({R)-3-{2-Ethyl-4-[5-(5-ethyl-6-isobutyl-pyridin-3-ylH1,2,4}oxadiazol-3-yl]-6-methyl- phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide; N-((S)-3-{2-Ethyl-4-[5-(5-ethyl-6-isobutyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl- phenoxy}-2-hydroxy-propyl)-2-hyd roxy-acetamide; (R)-3-{2-Ethyl-4-[5-(6-isopropoxy-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl- phenoxy}-propane-1,2-diol; (S)-3-{2-Ethyl-4-[5-{6-isopropoxy-5-methyl-pyridin-3-ylH1,2,41oxadiazol-3-yi]-6-methyl-phenoxy}-propane-1,2-diol; N-((R)-3-{2-Etliyl-4-[5-{6-isopropoxy-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yi]-6-methyl-phenoxy}-2-hyd roxy-propy I )-2-hyd roxy-a cetam id e; N-((S)-3-{2-Ethyl-4-[5-{6-isopropoxy-5-methyl-pyridin-3-yl)-I1,2,4]oxadiazol-3-yl]-6-methyI-phenoxy}-2-liyd roxy-propy I )-2-hyd roxy-acetam ide; 3M;2-bthyi^5-(6-isopropoxy-5-methyliDyridin-S-y;H1_2,4iDxafflazo:-3-yil-6-meinyJ-phenyt}-N-/2-r-i yd ro xy-etnyI^)-proptonamide; (R)-3-{2-Ethyl-4-[3-{6-isopropoxy-5-methyl-pyridfn-3-ylH''.2,4]axadiazol-5-yl]-6-methy|-phenoxy}-propane-1,2-diol; (S)-3-{2-Ethyl-4-[3-(6-isopropoxy-5-methy(-pyridin-3-y/)-[1,2,4jaxadJazGK5-ylI-6-methyi-phenoxy}-propane-1,2-diol; and 3-{2-Efhyl-4-[5-(6-isopropoxy-5-methyl-pyridin-3-yl)-[1,2.4]oxadiazol-3-yl]-6-methyi-phenyl}-propionic acid. xxxvi) A further aspect of the invention relates to novel pyridin-3-yl derivatives of Formula (II) 4 CH2-{CH2)n-COOH Formula (II) wherein A, R', R^, and n are as defined in claim 1; R^ represents hydrogen; R** represents C^-alkyl, or Ci-4-alkoxy; and R^ represents Ci-,-alkyl, or halogen. The compounds of Fomiula (I) and their pharmaceutically acx^ptable salts can be used as medicaments, e.g. in the form of pharmaceutical compositions for enteral or parental administration. The production of (he pharmaceutical compositions can be effected in a manner which will be familiar to any person skilled in the art (see for example Mark Gibson, Editor, Pharmaceutical Preformulation and Fonnulation, IHS Health Group, Englewood, CO, USA, 2001; Remington, The Science and Practice of Ptiannacy, 20th Edition, Philadelphia College of Pharmacy and Science) by bringing the described compounds of Formula (I) or their pharmaceutically acceptable salts, optionally in combination with other therapeutically valuable substances, into a galenical administration form together with suitable, non-toxic, inert, pharmaceutically acceptable solid or liquid carrier materials and, if desired, usual pharmaceutical adjuvants. The phamiacautical compositions comprising a comDOLinc of FormLiia i'U ars useful for the prevention and'or treatment of diseases or disorosfs assaz^.^:^ ATT- an acovatad Immune system. Such diseases or disorders are selected from the group consisting of rejection of transplanted organs, tissue or ceils; graft-versus-host diseases brought about by transplantation; autoimmune syndromes including rheumatoid arthritis; systemic lupus erythematosus; antiphospholipid syndrome; Hashimoto's thyroiditis; lymphocytic thyroiditis; multiple sclerosis; myasthenia gravis; type I diabetes; uveitis; episcleritis; scleritis; Kawasaki's disease, uveo-retinitis; posterior uveitis; uveitis associated with Behcet's disease; uveomeningitis syndronne; allergic encephalomyelitis; chronic allograft vasculopathy; post-infectious autoimmune diseases including rheumatic fever and post¬infectious glomerulonephritis; inflammatory and hyperproliferative skin diseases; psoriasis; psoriatic arthrifis; atopic dermatitis; myopathy; myositis; osteomyelitis; contact dermalilis; eczematous dermatitis; seborrhoeic dermatitis; lichen planus; pemphigus; bullous pemphigoid; epidermolysis bullosa; urticaria; angioedema; vasculitis; erythema; cutaneous eosinophilia; acne; scleroderma; alopecia areata; keratoconjunctivitis; vernal conjunctivitis; keratitis; herpetic keratitis; dystrophia epithelialis corneae; corneal leukoma; ocular pemphigus; Mooren's ulcer; ulcerative keratitis; scleritis; Graves' ophthalmopathy; Vogt-Koyanagi-Harada syndrome; sarcoidosis; pollen allergies; reversible obstructive ainway disease; bronchial asthma; allergic asthma; intrinsic asthma; extrinsic asthma; dust asthma; chronic or inveterate asthma; late asthma and airway hyper-responsiveness; bronchiolitis; bronchitis; endometriosis; orchitis; gastric ulcers; ischemic bowel diseases; inflammatory bowel diseases; necrotizing enterocolitis; intestinal lesions associated with thermal bums; coeliac disease; proctitis; eosinophilic gastroenteritis; mastocytosis; Crohn's disease; ulcerative colitis; vascular damage caused by ischemic diseases and thrombosis; atherosclerosis; fatty heart; myocarditis; cardiac infarction; aortitis syndrome; cachexia due to viral disease; vascular thrombosis; migraine; rhinitis; eczema; interstitial nephritis; IgA-induced nephropathy; Goodpasture's syndrome; hemolytic-uremic syndrome; diabetic nephropathy; glomerulosclerosis; glomerulonephritis; tubulointerstitial nephritis; interstitial cystitis; multiple myositis; Guillain-Barre syndrome; Meniere's disease; polyneuritis; multiple neuritis; myelitis; mononeuritis; radiculopathy; hyperthyroidism; Basedow's disease; thyrotoxicosis; pure red cell aplasia; aplastic anemia; hypoplastic anemia; idiopathic thrombocytopenic purpura; autoimmune hemolytic anemia; autoimmune thrombocytopenia; agranulocytosis; pernicious anemia; megaloblastic anemia; anerythroplasia; osteoporosis; fibroid lung; idiopathic interstitial pneumonia; dermatomyositis; leukodemia vulgaris; ichthyosis vulgaris: photoallergic sensrtivrty: cutaneous T -cei; rymphoma: poryartsritis nodosa: Huntington's chorea: Sydenhan-.'s chorsa- r-ryoca-Dcss- -^/.ocardms: scieroderma: Wegener's granuloma; Sjogren's syndrome; adiposis; eosinophilic fascitis; lesions of gingiva, perfodontium, alveolar bone, substantia ossea dentis; male pattern alopecia or alopecia senilis; muscular dystrophy; pyoderma; Sezar/s syndrome; hypophysitis; chronic adrenal inst/fficiency; Addison's disease; ischemia-reperfusion injury of organs which occurs upon preservation; endotoxin shock; pseudomembranous colitis; colitis caused by drug or radiation; ischemic acute renal insufficiency; chronic renal insufficiency; lung cancer; malignancy of lymphoid origin; acute or chronic lymphocytic leukemias; lymphoma; pulmonary emphysema; cataracta; siderosis; retinitis pigmentosa; senile macular degeneration; vitreal scarring; corneal alkali bum; dermatitis erythema; ballous dermatitis; cement dermatitis; gingivitis; periodontitis; sepsis; pancreatitis; peripheral artery disease; carcinogenesis; solid cancer tumors; metastasis of carcinoma; hypobaropathy; autoimmune hepatitis; primary biliary cirrhosis; sclerosing cholangitis; partial liver resection; acute iiver necrosis; cirrhosis; alcoholic cirrhosis; hepatic failure; fulminant hepatic failure; late-onset hepatic failure; and "acute-on-chronic" liver failure. Preferred diseases or disorders to be treated and/or prevented w/ith the compounds of Formula (!) are selected from the group consisting of rejection of transplanted organs such as kidney, liver, heart, lung, pancreas, cornea, and skin; graft-versus-host diseases brought about by stem cell transplantation; autoimmune syndromes including rheumatoid arthritis, muttipte sclerosis, inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, psoriasis, psoriatic arthritis, thyroiditis such as Hashimoto's thyroiditis, uveo-retinitis; atopic diseases such as rhinitis, conjunctivitis, demiattis; asthma; type I diabetes; post¬infectious autoimmune diseases including rheumatic fever and post-infectious glomerulonephritis; solid cancers and tumor metastasis. Particularly preferred diseases or disorders to be treated and/or prevented with the compounds of Formula (I) are selected from the group consisting of rejection of transplanted organs selected from kidney, liver, heart and lung; graft-versus-host diseases brought about by stem cell transplantation; autoimmune syndromes selected from rheumatoid arthritis, multiple sclerosis, psoriasis, psoriatic arthritis, Crohn's disease, and Hashimoto's thyroiditis; and atopic dermatitis. The present invention also relates to a method for the prevention or trsatment of 3 disease or disorder mentioned herein comprising adminisienr-g :i; = suc-eo: a pharmaceijiically active amount of a compound of Formula (I)- Furthennore, compounds of the Formula (!) are also useful, in combination with one or several immunomodulating agents, for the prevention and/or treatment of the diseases and disorders mentioned herein. According to a preferred embodiment of the invention, said agents are selected from the group consisting of immunosuppressants, corticosteroids, NSAID's, cytotoxic drugs, adhesion molecule inhibitors, cytokines, cytokine inhibitors, cytokine receptor antagonists and recombinant cytokine receptors. The present invention also relates to the use of a compound of Formula (I) for the preparation of a pharmaceutical composition, optionally for use in combination with one or several immunomodulating agents, for the prevention or treatment of the diseases and disorders mentioned herein. The compounds of Formula (I) can be manufactured by the methods given below, by the methods given in the Examples or by analogous methods. Optimum reaction conditions may vary with the particular reactants or solvents used, but such conditions can be determined by a person skilled in the art by routine optimisation procedures. Compounds of the Formula (I) of the present invention can be prepared according to the general sequence of reactions outlined below. Only a few of the synthetic possibilities leading to compounds of Formula (1) are described. Structure 1 Structure 2 In case A represents -CO-CH=CH-, the compounds of Formula (I) may be prepared by reacting a compound of Structure 1 with a compound of Structure 2 in the presence of a base or an acid. The functional groups present in the residues R^ to R** may require temporary protection or may even be introducsd Ln aadiDor.B- steps thai foiiow the condensation reaction. Compounds of Formuia ;. wr^Bir. A reoresenis -CC-CH^-CH;-may be prepared by reacting a compound of Formula (j) wherein A represents -CO-CH=CH- with hydrogen in the presence of a catalyst such as Pd/C, Pt'C, PtO;. etc. in a solvent such as EtOH, MeOH, THF. etc. or mixtures thereof. N—O Structure 3 Structure 4 Compounds of Structure 1 may be prepared by reacting a compound of Structure 3 with a methyl Grignard reagent or by treating a compound of Structure 4 with 2 eq. of methyllithium in a solvent such as ether, THF. etc. at temperatures between -20 and 50°C. The Weinreb amide compound of Structure 3 is prepared by treating a compound of Structure 4 with N, 0-di methyl hydroxy lam ine hydrochloride in the presence of coupling reagent such as EDC, DCC, etc. (M. Mentzel, H. M. R. Hoffmann, N-Methoxy N-melhyl amides (Weinreb amides) in modern organic synthesis, Journal fuer Praktische Chemie/Chemiker-Zeitung 339 (1997). 517-524; J. Singh, N. Satyamurthi, I. S. Aidhen, The growing synthetic utility of Weinreb's amide, Journal fuer Praktische Chemie (Weinheim, Germany) 342 (2000) 340-347; V. K. Khiestkin, D. G. Mazhukin, Recent advances in the application of N,0-dialkylhydroxylamines in organic chemistry. Current Organic Chemistry 7 (2003), 967-993). Structure 5 Compounds of Formula (I) wherein A represents -C0-NH-CH2- may be prepared by coupling a compound of Structure 5 with a compound with Structure 4 by using a coupling reagent such as EDC, DCC, TBTU, PyBOP, etc. or by coupling a compound of Structure 5 with the corresponding acid chloride or bromide of a compound of Structure 4. Compounds of Formula (I) which represent a 5-pyTldin-3-y:-["; .Z4jGx3d;azoie derivative, are prepare^d by reacting a 'Compound of Stnjcturs 5 \r a so^am sucr as dicxane THF. DME. xylene, toluene, benzene, pyridine, DMF, DCM, acetic acid, TFA, etc, at rt or elevated temperatures in the presence or absence of auxiliaries such as acids (e.g. TFA, acetic acid, HCI, etc.), bases (e.g. NaH, NaOAc, NajCOa, K2CO3, NEta, etc.), tetraalkylammonium salts, or water removing agents (e.g. oxalyl chloride, a carboxylic acid anhydride, POCI3, PCI5, P4O10, molecular sieves, Burgess reagent, etc.) (Lit: e.g. A. R. Gangloff, J, Litvak, E. J. Shelton, D. Sperandio, V. R. Wang, K. D. Rice, Tetrahedron Lett. 42 (2001), 1441-1443; T. Suzuki, K. Iwaoka, N. Imanishi, Y. Nagakura, K. Miyta, H. Nakahara, M, Ohfa, T. Mase, Chem. Pharm. Bull. 47 (1999), 120-122; R. F. Pouiain. A. L. Tartar, B. P. Deprez, Tetrahedron Lett. 42 (2001), 1495-1498; R. M. Srivastava, F. J. 8. Oliveira, D. S. Machado, R. M. Souto-Maior, Synthetic Commun. 29 (1999). 1437-1450; E. O. John, J. M. Shreeve, Inorganic Chemistry 27 (1988), 3100-3104; B. Kaboudrn, K. Navaee, Heterocycles 60 (2003), 2287-2292). Structure 6 N^ .0 Compounds of Structure 6 may be prepared by reacting a compound of Structure 4 with a compound of Structure 7 in a solvent such as DMF, THF, DCM, etc. in the presence or absence of one ore more coupling agents such as TBTU, DCC, EDC, HBTU, HOBt, CDI, etc. and in the presence or absence of a base such as NEta, DiPEA, NaH, K2CO3. etc. (Lit: e.g. A. Hamze, J.-F. Hernandez, P. Fulcrand, J. Martinez, J. Org. Chem. 68 (2003) 7316-7321; and the literature cited above). HO—NH Structure 7 Compounds of Formula (I) which represent a 3-pyndir=-3-yH1^,4}cxad;s2ate cienvativs are prepared in an analogous fashion (Lit. e.g. C. T, Brain. ^. W. =^si^.. "-". _3Qng. P. _. Oakley. Tetrahedron Lett. 40 (1999) 3275-3278) by reacting a compound of Structure 8 wiih a compound of Structure 9 and subsequent cyciisation of the corresponding hydroxyamidine ester intermediate. Structure 8 Structure 9 Compounds of Structure 7 and 8 may be prepared by reacting a compound of Structure 10 and 11, respectively, with hydroxylamine or one of its salts in a solvent such as MeOH, EtOH, pyridine, etc. in the presence or absence of a base such as Na2C03, K2C03, NEts, KOtBu, etc. {Lit: e.g. T, Suzuki, K. Ivi/aoka, N. Imanishi, Y. Nagakura, K. Miyta, H, Nakahara, M. Ohta, T. Mase, Chem. Pharm. Bull. 47 (1999), 120-122; J. Cui. D. Crich, D. Wink, M. Lam, A. L. Rheingold, D. A. Case, W. T. Fu, Y. Zhou, M. Rao, A. J. Olson, M. E. Johnson, Bioorg. Med. Chem. 11 (2003), 3379-3392; R. Miller, F. Lang, Z. J. Song, D. Zewge, WO 2004/035538 (Merck & Co., Inc., USA); B. Kaboudin, K. Navaee, Heterocycles 60 (2003). 2287-2292). Structure 10 StnjctureH Depending on the nature of the functionalities present in the residues R^ to R* in Structures 2, 5, 6, 7, 9, and 10, these functionalities may require temporary protection. Appropriate protecting groups are known to a person skilled in the art and include e.g. a benzyl or a trialkylsilyl group to protect an alcohol, a ketal to protect a diol, etc. These protecting groups may t>e employed according to standard rr^etrtodoJogy ;s.g. ;. W. GrBSne. P. G. M, Wuts. P-otsctive Groups in Organic Synthesis, 3~ EdftiD'-;. ;v^> \e* York. i99r P J. Kocienski, Protecting Groups, Thieme Stuttgart, 1994). AStematively. the desired residues R^ to R^, in particular R^, may also be introduced in later steps that follow ths coupling of the pyridine compounds of Structure 1, 4, 8 or 11 with the phenyl derivatives of Stucture 2, 5, 7, 9 or 10 by using a suitable precursor of a compound of Structure 2, 5, 7, 9 and 10-The phenyl compounds of Structure 2, 5, 7, 9 and 10 or their precursors are either commercially available or are prepared according to procedures known to a person skilled in the art. HN—NH Structure 13 O Structure 12 Compounds of Formula (I) which represent a 2-pyridin-3-yi-[1,3,4]oxadiazole or a 2-pyridin-3-yl-[1,3,4]thiadiazole derivative are prepared similarly by reacting a compound of Structure 4 with hydrazine (by using a coupling reagent such as TBTU, DCC, EDC, HBTU, PyPOB, HOBf, CD), etc.) to form a compound of Structure 12 which is then coupled with a compound of Structure 9 to give a compound of Structure 13. A compound of Stnjcture 13 can also be prepared by following the reverse reaction order i.e. by first coupling a compound of Stmcture 9 with hydrazine followed by reacting the corresponding hydrazide intermediate with a compound of Structure 4. Dehydration of a compound of Stnjcture 13 to form the desired 2-pyridin-3-yl-[1.3,4]oxadiazo!e derivative is affected by treating a compound of Structure 13 with a reagent such as POCI3, CCU or CBr^ in combination with PPhs. P2O5, Burgess reagent, etc. in a solvent such as toluene, MeCN, dioxane, THF, CHCI3. etc. at temperatures between 20 and 120''C in the presence or absence of microwave irradiation. {Lit. e.g. M. A, Garcia, S. Martin-Santamaria, M. Cacho, F. Moreno de la Llave, M. Julian, A, Martinez. B, De Pascual-Teresa. A. Ramos, J. Med. Chem. 48 (2005) 4068-4075, C. T. Brain, J. M. Paul, Y. Loong, P. J. Oakley, Tetrahedron Lett. 40 (1999) 3275-3278). Likewise, 2-pyridin-3-yl-[1,3,4]thiadiazole derivatives are obtained by cyclising a compound of Sturcture 13 with Lawesson's reagent optionally in combination with P2S5 in the presence or absence of a solvent such as pyridine, toluene, THF, MeCN, etc. at elevated temperatures with or without mtcrowave irTadlaiia- .;LJL e.g. A. A. Kirsanov. P- Samoson. A. J. Seed. J Org_ Chem- 66 '2^X1 ■ 7S25-~'B2B-.. Structured Compounds of Formula (I) which represent a 5-pyridin-3-yl-oxazoie or a 5-pyridin-3-yl-thiazole derivative are prepared by treating a compound of Structure 14 either with POCls, PCIs, I2 in combination with PPhs and NEtg, trifluoroacetic anhydride, Burgess reagent, etc. in a solvent such as toluene, benzene, dioxane, THF, etc. at temperatures between 20 and 120°C or with Lawesson's reagent optionally in combination with P2S5 in the presence or absence of a solvent such as pyridine, toluene, THF, MeCN, etc. at elevated temperatures with or without microwave irradiation as mentioned above (Lit. e.g. N. Sato, T. Shibata, M. Jitsuoka, T. Ohno, T. Takahashi, T. Hirohashi, T. Kanno, H. Iwaasa, A. Kanatani, T. Fukami, Takehiro Bioorg. & Med. Chem. Lett. 14 (2004) 1761-1764). The compounds of Structure 14 are prepared by reacting a compound of Structure 15 with a compound of Structure 9. The aminoketon of Structure 15 can be prepared from a compound of Structure 1 by procedures given in the literature (e.g. J. L. LaMattina, J. Heterocyclic Chem. 20 (1983) 533-538; M. Pesson, M. Antoine, P. Girard, J. L. Benichon. S. Chabassier, P. De Lajudie. S. Parte, F. Roquet, G. Montay, Eur. J. Med. Chem. 15 (1980) 263-268). Compounds of Formula (I) which represent a 2-pyridin-3-yl-oxa2ole or a 2-pyridin-3-yl-thiazole derivative are prepared in an analogues fashion from a compound of Structure 16 and a compound of Structure 4. HoN Structure 15 Structure 16 MematTi'eJy, the txjnds between the pyridine DT trre phenytnrrg an-d th* cenira; 5-membered heteroaromatic ring can also be foiTnec ~-v soDf-zn-z zaiszrj.^ catatvsec cress coupling reactions. Methods that effect the transformation of a compound of Structure 4 into a compound of Structure 11, or the opposite, are known to a person skilled in the art. Compounds of the Structure 4 may be prepared by reacting a 5,6-dichloronicotinic acid ester with an alkyl Grignard reagent in the presence of Fe(acac)3 in a solvent such as THF, dioxane, DMF, NMP, etc., or combinations thereof, at temperatures ranging from -78 to 25°C (Furstner conditions. Lit. e.g. A. Fiirstner, A. Leitner, M. Mendez, H. Krause J. Am. Chem. Soc. 124 (2002) 13856-13863; A. Furstner, A. Leitner Angew. Chem. 114 (2002) 632-635). The reaction conditions can be chosen such that either the 5-cliloro-6-alkyi-nicotintc acid ester or the 5,6-dialkyl-nicotinic acid ester is obtained as the main product. The two chlorine atoms in a 5,6-dichloronicotinic acid ester may also be substituted either sequentially or in one step by two alk-1-enyl groups, which may be the same or different, by treating 5,6-dichloronicotinic acid ester with the appropriate alkenyl boron derivative under Suzuki coupling conditions known to a person skilled in the art. The obtained 5,6-di-alkenyl-nicotinic acid ester is hydrogenated to the corresponding 5,6-dialkyl-nicotinic acid ester. In addition, a procedure in which the Furstner and the Suzuki conditions are employed sequentially can be envisaged. The 5,6-dichloronicotinic acid ester may also be treated with an alcohol or an aicoholate at elevated temperatures to furnish the corresponding 5-chloro-6-alkoxy-nicotinic acid esters. Finally, cleavage of the ester functionality delivers the compounds of Structure 4. Alternatively, compounds of Structure 4, wherein R' represents a methyl group, can be prepared from a compound of Structure 17 via formation of the corresponding 6-chloro-5-methyl-nicotinic acid esters using methods well known in the art, followed by derivatisation using Furstner or Suzuki conditions as described above and subsequent cleavage of the ester function. The compound of Structure 17 can be prepared from known 6-chloro-3-formyl-5-methyl-pyridine (Lit. e.g. EP-0702003) by oxidation of the formyl group to the carboxylic acid using oxidation reagents well known in the art such as aq. H2O2 in formic acid, KMn04, etc. in the presence or absence of a solvent such as toluene, THF, MeCN, acetone, etc. at temperatures between 0 and 120''C. Compounds of Structure 11, wherein R'' represents a methyl group, can alternatively be prepared as described above from compounds of Structure 4. wherein R'' represenls a netnyi gmup: D-- according tc riferature methods -Lit; e.g. J.B.Paine 111, J. Heterocyclic Oie^.. 1987, 35'-S55 . Structure 17 Whenever the compounds of formula (I) are obtained in the form of mixtures of enantiomers, the enantiomers can be separated using methods known lo one skilled in the art: e.g. by formation and separation of diastereomeric salts or by HPLC over a chirat stationary phase such as a Regis Whelk-01(R,R) (10 jim) column, a Daicel ChiralCel OD-H (5-10 Jim) column, or a Daicel ChiralPak lA (10 |im) or AD-H (5 um) column. Typical conditions of chiral HPLC are an isocratic mixture of eluent A (EtOH, in presence or absence of an amine such as NEts, diethylamine) and eluent B (hexane), at a flow rate of 0.8 to ISOmUmin. Experimental part II Chemistry The following examples illustrate the invention but do not at all limit the soape thereof. Af( temperatures are stated in "C. Compounds are charBcCerized by ^H-NMR (300 MHz) or ^^C-NMR (75 MHz) (Varian Oxford; chemical shifts are given in ppm relative to the solvent used; multiplicities: s = singlet, d = doublet, t = triplet; p = pentuplet, hex = hexet, hept = heptet, m = multiptet, br = broad, coupling constants are given in Hz); by LC-MS (Finnigan Navigator with HP 1100 Binary Pump and DAD, column: 4.6x50 mm, Zorbax SB-AQ, 5 j^m, 120 A, gradient: 5-95% MeCN in water, 1 min, with 0.04% TEA, flow: 4.5 mL/min), tR is given in min, (retention times marked with " or as LC-MS* refer to LG run under basic conditions, i.e. eluting with a gradient of MeCN in water containing 13 mM of ammonium hydroxide, other wise identical conditions); by TLC {TLC-plates from Merck, Silica get 60 BTve HP'^ ioolumr,: X-terra F254}: or by melting point. Compounds are purified by prepar RP18, 50x19 mm. 5 .Lim. gradient: 10-95% MeCN ;- WSTBT 3oriiHL-irc ;.5 --of formic add) or by MPLC (Labomatic MD-80-100 pump, Linear UVIS-201 detector coiumn: 350x18 mm, Labogel-RP-18-5s-10G, gradient: 10% MeOH in water to 100% MeOH). Racemates can be separated into their enantiomers by preparative HPLC {column: ChiralPaK AD 20x250 mm. 5 [im, 15% Eton in liexane). Abbreviations (as used lierein): aq. atm BSA Burgess reagent CC aqueous atmosphere bovine serum albumin methoxycarbonylsulfamoy! triethytammonium hydroxide column chromatography GDI carbonyl diimidazole DCC dicyclohexyl carbodiimide DCM dichioromethane DEAD diethyl-dtazodicarboxylate DIPEA HiJning's base, diethylisopropylamine DME 1,2-dimethoxyethane DMF dimethylformamide DMSO dimethylsulfoxide dppf 1,1'-bis{diphenylphosphino)ferrocene EA ethyl acetate EDO N-{3-dimethylaminopropyl)-N'-ethyl-carbocliimide ether diethyl ether EtOH ethanol Fe{acac)3 iron(lll) acetylacetone-complex h hour(s) HBTU 0-(benzotria2ol-1-yl)-N,N,N',N"-tetramethyluronium hexafluorophosphate HOBt 1 -hydroxy-benzotriazole HPLC high performance liquid chromatography HV high vacuum conditions Lawesson's reagent 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide LC-MS liquid chromatography - mass spectrometry MeCN acetonitrile MeOH methgno) min minute(s) MPLC medium pressure liquid chromatography NaOAc sodium acetate NEts triethylamine NMO N-methyl-morpholine-N-oxide NMP 1 -methyl-2-pyrrolidone OAc acetate org. organic Ph phenyl PPha triphenylphosphine PyBOP benzotriazol-1-yl-oxy-tris-pyrrolidino-phosphonium- hexafluoro-phosphate prep. preparative rac racemjc rt room temperature sat. saturated SIP sphingosine 1-phosphate TBME tert.-butyl methyl ether TBTU 2-(1H-benzotria2ole-1-yl)-1.2,3,3-tetramethyluronium tetrafluoroborate tert. tertiary TFA trifluoroacetic acid THF tetrahydrofuran TLC thin layer chromatography tR retention time Synthesis of Intermediates Nicotinic acid 1 5,6-DichIoronicotinic acid (1.95 g, 10 mmoi) is added to = sc^Jtbr -: KOtBu fZ25 z 2-"^ mmol) in isopropanol (20 mL). The mixture is heated a: 3C=C ^' ■; n. The mJxEjre is diluted with water (60 mL) and acidified with 1M aq. HCi. The aq. solution is extracted with ether (5 x 50 mL) and the combined org. extracts are dried (Na2S04). filtered and evaporated to provide 5-chIoro-6-isopropoxy-nicotinicacid; 'H NMR (d^-DMSO) S^.38 (d, J = 6.2 Hz, 7 H), 5.44 (hept, J = 6.2 Hz, 1 H), 8,18 (d, J = 2,1 Hz, 1 H), 8.65 (d, J = 2.1 Hz, 1 H) Nicotinic acid 2 a) A suspension of 5,6-dichloronicotinic acid (5.25 g, 27,3 mmol) in toluene (200 mL) is heated to SO^C and then slowly treated with N,N-dimethylfonnamide di-terl. butyiacetal (20.0 g, 98.0 mmol). The mixture becomes slightly yellow and clear. Heating and stirhng is continued for 3 h before the solution is cooled to rt, diluted with ether and washed with sat, aq. Na2C03-solution. The org. phase is dried over MgS04, filtered and the solvent is evaporated. The residue is purified by MPLC (Si02) to give 5,6-dichloronicotinic acid tert.- butyl ester (5.13 g). 'H NMR (CDCI3): 6 1.62 (s, 9 H), 8.30 (d, J = 2.0 Hz, 1 H), 8.83 (d. J = 2.0 Hz, 1 H). b) To a solution of 5,6-dichloronicotinic acid tert.-butyt ester (3.37 g, 13.6 mmol). Fe(acac)3 (719 mg, 2.04 mmol) and NMP (1.95 mL, 20 mmol) in THF (300 mL). a solution of methyl magnesium chloride in THF (3M, 5.4 mL, 16.3 mmol) is slowly added at -78''C. The brown solution turns turbid and black. Stimng is continued for 1 h at -75''C before it is warmed to CC. The reaction is incomplete and the mixture is cooled again at -7D°C. A further batch of methylmagnesium bromide In THF (3M, 5.4 mL, 16.3 mmol) is slowly added at -70''C. The dark green mixture is slowly warmed to -20''C and carefully quenched with 0.7 N aq. HCI (150 mL). The mixture is extracted with ether (5 x 60 mL). The combined org. extracts are dried over Na3S04, filtered and evaporated to give crude 5-chloro-6-methyl-nicotinic acid tert.-butyl ester as a yellow oil (4.66 g); LC-MS; tp = 1.03 min, [M+lf = 228.22, c) 5-Chloro-6-methyl-nicotinic acid tert.-butyl ester (3.09 g, 13.5 mmol), Fe(acac)3 (719 mg, 2.04 mmol) and NMP (1.95 mL, 20 mmol) are dissolved in THF (3M, 500 mL) and cooled at -Td'C. A soJution of isobutylmagnesium bromide in THF (ZM. 13.6 —.mci) ;= si-owiy acfcjed 3t -75X. T.he D-Dwn solution turns turbid and yefJo* Strrng s :x>"r:_.ac :'3r ' ? s: -~5=C before it is slowly warmed to rt. The reaction is incomplete, further Fs(acac); (719 mg, 2.04 mmol) is added and the mixture is cooled again at -JO^C. Further methylmagnesium bromide in THF (2M, 13.6 mmol) is slowly added at -/CC. The dark green mixture is slowly warmed to rt and stirred for 15 h. The mixture is carefully quenched with 0.7 N aq. HCI (150 mL). The mixture is extracted with EA (6 x 60 mL). The combined org. extracts are dried over Na2S04, filtered and evaporated. The residue is purified by reversed phase MPLC to give 6-metlnyl-5-isobutyl-nicotinic acid tert.-butyl ester as black oil (0.50 g); LC-MS: tR = 0.84 min, [M+ir = 250.14, d) A solution of 6-methyl-5-isobutyl-nicotinic acid tert.-butyl ester (0,50 g, 2 mmol) is dissolved in dioxane (20 mL) and 4 N HCI in dJoxane (30 mL) is added. The mixture is stirred for 3 h. The solvent is evaporated to give 6-methyl-5-isobutyl-nicotinic acid hydrochloride (0,52 g); LC-MS: tR = 0,54 min; [M+ir =194,29; 'H NMR (d^-DMSO) 5 0,91 (d, J = 6,5 Hz, 6 H), 1,91 (hept J = 6.5 Hz), 2,68 (d, J = 7,3 Hz, 2 H). 2.73 (s, 3 H), 8,47 (d, J=1,8H2, 1 H), 8,90 (d, J =2,0 Hz. 1 H). Nicotinic acid 3 a) To a solution of 5,6-dichloronicotinic acid tert.-butyl ester {5.00 g, 20.0 mmol), and 2,4,6-trivinylcyclotriboroxane pyridine complex (9.700 mg, 40 mmol) in dioxane (30 mL), a solution of 2 M aq. KzCOa (6 mL) followed by Pd(PPh3)4 (620 mg, 0.38 mmol) and PPha (620 mg, 3.8 mmol) is added. The mixture is stirred at 100°C for 2 h, cooled to rt and diluted with ether (200 mL). The mixture is extracted with 1M aq. NaOH (2 x 50 mL) and brine (50 mL). The org. phase is dried (Na2S04), filtered and evaporated. The residue is purified by FC (Si02, EA-heptane) to give 5-chloro-6-vinyl-nicotinic acid tert.-butyl ester (4.0 g) as a yellow oil; LC-MS: IR = 1.05 min, [M+l+CHaCNf = 281.36. b) A mixture of 5-chloro-6-vinyl-nicotinic acid tert.-butyl ester (2.0 g), CsjCOs (3.4 g), tri(tert.-butyl)phosphine (0,04 eq,), tris(dibenzylidenacetone)dipalladium (0.02 eq,), and 2,4,6-trivinylcyclotriboroxane pyridine complex (2.0 g) in dioxane (30 mL) is degassed and heated at 100°C for 15 h. The mixture is cooled to rt, and diluted with ether (200 mL). The mixture is extracted with 1M aq. NaOH (2 x 5C mL) and brine [5C mL.. Tne org. phase is dried (Na2S0^'i- filtered and evaporated. The rssiaue s Djrtnec z\ -C S-O-, E-,-rrec-3">S: to give 5,6-divinyl-nicotinic acid tert.-butyl ester (0.89 g) as an oil. LC-MS: IR = 1.01 min, [M+lf = 232.04. ■c) To a solution of 5,6-divinyl-nicotinic acid tert-butyl ester (890 mg, 3.8 mrtiol) in THF (20 mL) containing some MeOH, Pd/C (100 mg, 10% Pd) is added and the mixture is stin-ed under 1 atm of Hj at rt for 3 h. The catalyst is filtered off and the filtrate is evaporated. The remaining residue is purified by FC (SiOa, EA-heptane) to give 5.6-diethyl-nicotinic acid tert-butyl ester (860 mg) as an oil; LC-MS: tp = 0.79 min. [M+lf = 236.14. d) A solution of 5,6-diethyl-nicotinic acid tert-butyl ester (860 mg, 3.65 mmol) in 6 N aq. HCI (15 mL) is stirred at 65°C for 3 h before the solvent is evaporated. The residue is dried under HV to give 5,6-diethyl-nicotinic acid hydrochloride (923 mg) as an oil; LC-MS; IR = 0.50 min, [M+ir= 180.05. Nicotinic acid 4 6-Ethyl-5-isobutyl-nicotinic acid is prepared in analogy to Nicotinic acid 3 from 5-chloro-6-vinyl-nicotinic acid tert.-butyl ester and 2,4,6-tri-(2-methyl-propenyl)-cycloboroxane pyridine complex, prepared in analogy to a procedure given by F. Kerins, D. F. O'Shea J. Org. Chem. 67 (2002) 4968^971); LC-MS: tp = 0.64 min, [M+lf =207.98. Nicotinic acid 5 a) A solution of 5,6-dichloronicotinic acid (5.0 g, 26 mmol) in dry EtOH (300 mL) and chlorotrimethylsiiane (33 mL, 10 eq.) is stirred at rt for 16 h. The solvent is evaporated, the residue dissolved in ether (200 mL) and washed w^ith a solution of saL aq. Na2C03 (75 mL) and brine (50 mL)- The org, phase is dried over NazSOi. TiitEr&d and ev^p-Drsted tc- give 5.&-dichlorori'COtinic add ethyi sster (5.8 g) as a sofic" ^Z-K'S: "_= = Z.B€ ~:n. [K'-r-j" = 219.93. b) To a solution of 5,6-dichloronicotinic acid ethyl est&r (0.8 g, 3.6 mmol), and 2,4,6-tri-(2-methyl-propenyj)-cyc!oboroxane pyridine complex (1.78 g, 5.49 mmol) in DME (20 mL), a solution of 2 M aq. K2C03 (5 mL) followed by Pd(PPh3)4 (50 mg. 0.068 mmol) and PPha (110 mg, 0.68 mmol) is added. The mixture is stirred at 100''C for 2 days before it is cooled to rt and diluted with ether (100 mL). The phases are separated and the aq. phase re-extracted with ether (50 mL). The combined org. extracts are washed wjtii 1M aq. NaOH (2 x 40 mL) and brine (40 mL), dried (Na2S04), filtered and evaporated. The crude product is purified by FC (Si02, EA-heptane) to give 5,6-di(2-methyl-propenyl)-nicotinic acid ethyi ester (52 mg) as a colourless oil; LC-MS;tR =1.11 min, [M+1]* = 260.24. c) 5,6-di(2-methyl-propenyl)-nicotinjc acid ethyl ester (52 mg, 0.3 mmol) is dissolved in TiHF (10 mL), Pd/C (20 mg, 10% Pd) is added and the mixture is stirred under 1 atm H2 at rt for 15 h. The catalyst is filtered off and the filtrate is evaporated to give 5,6-diisobutyl-nicotinic acid ethyl ester (52 mg) as an oil; LC-MS: ts = 1.12 min, [M+1]* = 264-19. d) A solution of 5.6-diisobutyI-nicotinic acid ethyl ester (52 mg, 0-2 mmol) in 6 N aq. HCl (2 mL) is stirred at 65°C for 15 h before it is cooled to rt and extracted with ether (2x10 mL). The aq. phase is evaporated and the residue is dried under HV to give 5,6-diisobutyl-nicotinic acid hydrochloride (012 g) as a colouriess solkl; LC-MS: IR = 0.73 min; [M+1]* = 236.40. Nicotinic acid 6 a) Phosphoroxychloride (183 mL, 2 mol) is heated at 90°C and a mixture of commercially available 2-methyl-2-butennitrile (73 g, 0.9 mol) and DMF (154 mL, 2 mol) is added slowly while keeping the temperature at 100 to llCC. The mixture is stirred at 110X for 15 h, cooled to rt and diluted with DCM (500 mL). The mixture is cooled at 0°C and carefully quenched with water (500 mL). The phases are separated and the aq. phase extracted with DCM (total of 800 mL). The combined org. extracts are dried (Na2S04), filtered and evaporated. The residue is crystallised from cydohexsne to provide S-^nroro-S-forrnyvS-methyl-pyridL-^ ^;2S.3 g) as slightfy yellow crystals- LC-MS -^ = Z.^z- ~r. TK'.-'T = 156.14. b)A solution of 6-chloro-3-formyl-5-methyl-pyridine (10 g, S4 mmol) in formic acid (200 mL) is cooled at OX and an aq. 50% wt solution of H2O2 in water (9.6 mL, 360 mmol) is added at this temperature. The mixture is stirred at OX for 15 h, carefully diluted with water {200 mL) and extracted with DCM (8 x 100 mL). The combined org. extracts are washed with 1M aq. HCI (100 mL) (check for remaining peroxide), dried (MgS04), filtered and evaporated. The residue is dried to give 6-ch!oro-5-methyl-nicotinic acid (9.56 g); LC-MS: tp = 0.72 min, [M+ir = 172.0. c) A solution of 6-ch[oro-5-methyl-nicotinic acid (13,85 g, 80.75 mmoi) in dry EtOH (200 mL) containing some drops of concentrated H2SO4 is stirred at reflux for 2 days. The solution is cooled to rt, the solvent evaporated, the residue dissolved in EA (2O0 mL) and washed with a solution of sat. aq. NasCOs (2 x 80 mL), 1M aq. KHSO4 (2 x 80 mL) and brine (50 mL). The org. phase is dried over MgS04, filtered and evaporated to give 6-chloro-5-methyl-nicotinic acid ethyl ester (12.65 g) as a solid; LC-MS: IR = 0.92 min; [M+lf = 200.10; 'H NMR(CDCl3)S1.43{L J = 7.0 Hz, 3 H), 2.46 (s, 3 H), 4.43 (q, J = 7.3 Hz, 2 H), 8.16(m, 1 H), 8.84 (d, J = 2.0 Hz, 1 H). d) To a solution of 6-chloro-5-methyl-nicotinic acid ethyl ester (4.98 g, 24.9 mmol), 2,4,6-tri-(2-methyl-propenyl)-cycloboroxane pyridine complex (5.74 g, 17.7 mmol, prepared in analogy to a procedure given by F. Kerins, D. F. O'Shea J. Org. Chem. 67 (2002) 4968-4971), and PPha (1.15 g, 4.4 mmol) in DME (60 mL), a solution of 2 M aq. K2CO3 (20 mL) is added. The mixture is degassed and flushed with N2 before Pd(PPh3)4 (460 mg, 0.4 mmol) is added. The mixture is stin-ed at 90°C for 20 h before it is cooled to rt, diluted with EA (150 mL) and washed with sat. aq. NaHCOa (2 x 50 mL). The org. extract is dried over MgS04, filtered and evaporated. The crude product is purified by PC (Si02, heptane-EA) to give 5-methyl-6-(2-methyl-propenyl)-nicotinic acid ethyl ester (3.98 g) as an orange oil; LC-MS: tR = 0.72 min, [M+lf = 220.15. e) 5-Methyl-6-(2-methyl-propenyl)-nicotinic acid ethyl ester (3.98 g, 18.2 mmol) is dissolved in THF (100 mL) and MeOH (100 mL), Pd/C (500 mg. 10% Pd) is added and the mixture is stirred under 1 atm H2 at rt for 15 h. The catalyst is filtered off and the filtrate is evaporated to give 6-isobutyl-5-methyl-nicotinic acid ethyl ester (3.76 g) as a colouriess oil; LC-MS: tR = 0.75min;[M+ir = 222.15;'HNMR(CDCi3)5 0.97(d, J=6.8Hz, 6H), 1.42 (t, J =7.3 Hz, 3 H), 2.20 (hept, J = 6.8 Hz, 1H). 2.38 (s, 3 H), 2.75 :d. J= T.C Hz. 2 H . 4.41 iq. J = ~ 3 Kz. 2H). 8.03 ('d. J = 1.8 Hz. 1 H). 9.00 (d. J = 2.GHz. l H . f) A solution of 6-isobutyl-5-methyl-nicotiniGacid ethyl ester (3.75 g, 15,95 mmol) in 12,5% aq. HCI (50 mL) is stirred at 65X for 24 h before the solvent is evaporated. The residue is dried under HV to give 6-isobutyl-5-methyl-nicotinic acid hydrochloride (3.55 g) as a white powder; LC-MS: t^ = 0.57 min, [M+lf = 194.25. Nicotinic acid 7 5-Methyl-6-propyl-nicotinic acid (1.85 g as hydrochloride) is prepared in analogy to Nicotinic acid 6 from 6-chloro-5-methyl-nicotinic acid ethyl ester (2.0 g) and commercially available frans-1-propen-1-yl broronic acid (1.3 g); ^H NMR (d^-DMSO) 5 0.96 (t, J = 7.3 Hz, 3 H), 1.72 (m, 2 H), 3.05 (t, J = 7.5 Hz. 2 H). 8.66 (m, 1 H), 8.86 (d, J = 1.5 Hz, 1 H). Nicotinic acid 8 S-lsobutyl-nicodnic acid is prepared in analogy to Nicotinic add 2 from commercially available 6-chloronicotinic acid ethyl ester and isobutylmagnesium chloride; LC-MS: tp = 0.52min,[M+1f= 180.30. Nicotinic acid 9 OH a) To a solution of 5,6-dichloronicotinic acid ethly ester (2.40 g, 10.9 mmol) and 2,4,6-tris-(2-methyl-propenyl)-cyclotriboroxane pyridine complex (2.02 g, 6.22 mmol, prepared in analogy to a procedure given by F. Kerins, D. F. O'Shea J. Org. Chem. 67 (2002) 4968-4971) in dioxane (40 mL) and 2 M aq. K2CO3 solution (10 mL), PPh3(114 mg, 0.436 mmol) is added. The mixture is degassed and put under N2 before Pd(PPh3)4 (160 mg, 0.218 mmol) is added. The mixture is stirred at 100X for 1.5 h before another portion of 2,4,6- tris-(2-methyUDrDpenyl)-cvclotribDroxane pyridtne comptex i'.OI 3. 3.'' mmoi; is sddec. Stirring is cor-Jnued at 100'C for 3 h before the mbdire 5 cooiec -J: -, :ii!L-&d wrtr. BC-^: washed with IN aq. NaOH solution followed by water, dried over MgSOi. filtered and concentrated. The crude product is purified by CC on silica gel eluting wtti heptane-EA 9.1 to give 5-chloro-6-(2-methyl-propenyl)-nicofinic acid ethyl ester (2.4 g) as an oil; LC-MS: tR = 1.05 min, [M+lf = 240.02. To a solution of this material in dioxane (40 mL), 2,4,6-trivinylcyclotriboroxane pyridine complex (1.84 g, 7.63 mmol), CS2CO3 (4.62 g. 14.2 mmol) followed by tri-fert-butylphosphine (88 mg, 0.436 mmol) is added. The mixture is degassed and put under Na before Pd2(dba}3 (200 mg, 0.218 mmol) is added. The mixture is stirred at 100°C for 16 h before another portion of 2,4,6-trivinylcydotriboroxane pyridine complex (1.84 g, 7.63 mmol) and Pd2(dba)3 (200 mg, 0.218 mmol) is added. Stirring is continued at 100°C for 24 h before the mixture is diluted with EA, washed with 1 N aq. NaOH solution, dried over MgS04, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 10:1 to give a first portion of 6-(2-methyl-propenyl)-5-vinyl-nicotinic acid ethyl ester. In addition, unreacted 5-chloro'6-(2-methyl-propenyl)-nicotinic acid ethyl ester is isolated. This material is again treated with 2,4,6-trivinylcyGlotriboroxane pyridine complex as described before. Work-up, purification and combining the two portions give 6-(2-methyl-propenyl)-5-vinyl-nicotinic acid ethyl ester (1.37 g) as an oil; LC-MS: t^ = 0.87 min, [M+ir = 232,13. b) To solution of 6-(2-methyl-propenyl)-5-vinyl-nicotinic acid ethyl ester (1.37 g, 6.74 mmol) in THF (20 nrL), Pd/C (100 mg, 10% Pd) followed by EtOH (20 mL) is added. The mixture is stirred under 1 atm of H2 at rt for 24 h. The catalyst is removed by filtration and the filtrate is concentrated. The crude product is purified by CO on silica ge! eluting with heptane;EA 4:1 to give 5-ethyl-6-isobutyl-nicotinic acid ethyl ester (970 mg) as a colourless oil, LC-MS: tR = 0.79 min, [M+ir = 236.20; ^H NMR (CDCU); .50.97 (d, J = 6.8 Hz, 6 H), 1.27 (t, 7= 7.5 Hz, 3 H), 1.42 (t, J = 7.0 Hz, 3 H), 2.17-2.28 (m, 1 H), 2.69-2.78 (m, 4 H), 4.42 (q, J = 7.0 Hz, 2 H), 8.07 (s, 1 H), 9.00(s, 1 H). c) A solution of 5-ethyl-6-isobutyl-nicotinic acid ethyl ester (970 mg, 4.12 mmol) in 25% aq. HCI is stirred at 95°C for 8 h. The solvent is evaporated and the residue is dried under high vacuum to give 5-ethyl-6-isobufyl-nicotinic acid hydrochloride (1.15 g, presumably as hydrate) as a colourless resin, LC-MS: tp = 0.62 min, [M+lj* = 208.35. Nicotinic acid 10 = OH 6-(3-Methyl-butyl)-nicotinic acid is prepared by reacting o-chioro-nicotinic acid tert-butly ester with 3-methyl-butylmagnesium bromide under Furstner conditions as described for Nicotinic acid 2; LC-MS: tR = 0.58min, [M+1]^= 194.30. Nicotinic acid 11 o- N- / OH a) To a solution of potassium tert. butylate (1,26 g, 11.3 mmol) in isopropanol {30 mL), 2,5-dibromo-3-picoline (2.89 g, 11.3 mmol) is added. The mixture is stirred at 80°C for 15 h before another portion of potassium tert.-butylate (2.53 g, 27.5 mmol) is added. Stirring is continued at 80°C for 24 h before the mixture is diluted with sat. aq. NaHCOa-solution. The mixture is extracted with ether, the org. extract is dried over MgS04, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 9:1 to give 5-bramo-2-isopropGxy'3-methyl-pyridine (1,24 g) as a colourless oil; LC-MS: IR = 1.06 min; [M+lf = 230.00; ^H NMR (CDCb): (J1,35 (d, J= 6.3 Hz, 6 H), 2.16 {s, 3 H), 5.27 (hepf, J = 6,3 Hz, 1H), 7,48 (d, J =1,5 Hz, 1 H), 8.02 (d, J = 2.0 Hz, 1 H). b) A solution of 5-bromo-2Hsopropoxy-3-methyl-pyridine (1,24 g, 5.39 mmol) and 2,4,6-trivinylcyclotriboroxane pyridine complex (1.27 g, 5.26 mmoi) in DME (12 mL) and 2 M aq. K2CO3 (5 mL) is degassed and put under argon before Pd(PPh3)4 (112 mg, 0,097 mmol) is added. The mixture is stirred at 80°C for 15 h t>efore it is cooled to rt. diluted with ether (50 mL), washed with sat. aq. NaHCOs solution (2x30 mL). dried over MgS04, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 9:1 to give 2-isopropoxy-3-methyl-5-vinyl-pyridine (703 mg) as pale yellow oil; LC-MS: IR = 1.01 min;[M+ir=178.11, c) To a solution of 2-isopropoxy-3-methyl-5-vinyt-pyridine (703 mg, 3.97 mmol) in acetone (80 mL), KMn04 (1.60 g, 10,1 mmol) is added and the mixture is stirred at rt for 18 h. The dark brown suspension is filtered and the clear, colourless filtrate is evaporated to dryness to give 6-tsopropoxy-5-methyl-nicotinic acid (1.06 g, as potassium salt) as an off-white solid: LC-MS: U = 0.86 min: [M-lf = 196.09; 'H NMR (D3O;: S^.3^ ,c. .■=5,3 Hz. 5 H; 2.14(3, 3 HI. 5.^5 (hept J = 7.0 Hz. IH). 7.91 (s. 1 H;. 5.:^ =. - -(- N-Hydroxy-e-isobutyl-S-methyl-nicotinamidine a) A solution of 6-isobuty]-5-methyl-nicotinic acid ethyl ester (2.86 g, 12.9 mmoij in 7 N NH3 in MeOH (80 mL) is stirred af 60°C for 20 h before the solvent is removed in vacuo. The residue is dried to give 6-isobutyl-5-methy!-nicotinamide (1.89 g) as a yellow oil; LC-MS: tp = 0.66 min, [M+1]^ = 193.29; 'H NMR (DB-DMSO): 50.91 (d, J = 6.5 Hz, 6 H), 2.08-2.20 (m, 1 H), 2.32 (s, 3 H), 2.65 (d, J = 7,3 Hz, 2 H), 7.43 (s, 1 H), 7.95 (s, 1 H). 8.01 (m, 1 H). 8.78 (s. 1 H). b) To a solution of 6-isobutyl-5-methyl-nicotinamide (1.89 g, 9.85 mmo!) in DCM (40 mL) and pyridine (2.83 g, 39.4 mmol), TFA anhydride (5.17 g, 24.6 mmol) is added portionwise at CC. The mixture is stirred at rt for 24 h, diluted with DCM and washed with water, 4% aq. citric acid solution followed by sat. aq. NaHCOa solution. The org. extract is dried over MgS04, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 9:1 to give 6-isobutyl-5-methyl-nicotinonrtrile (1.35 g) as a white solid; LC-MS: \R = 0.89 min, [M+lf = 175.11. c) To a solution of potassium tert-butylate (3.04 g, 27.1 mmol) in MeOH (60 mL), hydroxylamine hydrochloride (1.62 g, 23.2 mmol) is added at 0°C. To this suspension, 6-(sobu£yI-5-methyl-n(COt)non(trile (1.35 g, 7.75 mn)o\) is added. The mixture is refluxed for3 h, cooled to rt. filtered and the filtrate is evaporated to dryness. The residue is suspended in a small amount of water and then extracted with EA. The org. extract is concentrated and dried under high vacuum to give N-hydroxy-6-isobutyl-5-methyl-nicotinamidine (1.53 g) as a pale yellow oil; LC-MS: tR = 0.68 min, [M+1]* = 208.22; 'H NMR (De-DMSO): ^-5-methyl-benzaldehyde; LC-MS: tR = 0.69 min, [M+lf = 241.10, 4-Ally1oxy-N-hydroxy-3,5-dimethyl-benzamidine HN HO^ 40 The title cximpound is prepared by aiiylating commerdaliy avafiati^ie 4-rTvctrcxy-3,5-dirT>ettTyr-benzonitrile with allyibromide in the presence of NaOH i- :soc-7zcsnz- =: -. ""-:■= nririie :s then transformed to the hydroxyamidine according to literature procedures (e.g. E. Meyer. A. C. Joussef, H. Gallardo, Synthesis 2003, 899-905); ^H NMR (CD3OD): 5 7.27 (s. 2 H), 6.10 (m, 1 H), 5.42 (m, 1 H), 5.26 (m. 1 H), 4.31 {dt, J= 5.6, 1.5 Hz. 2 H). 2.29 (s, 6 H). 4-Altyloxy-3-ethyl-N-hydroxy-5-methyl-benzamidine HN H0-. 0 The title compound is prepared by allylating 3-ethyl-4-hydroxy-5-methyl-benzaldehyde which is prepared from 2-ethyl-6-methyl-phenol following literature procedures (see 3-ethyl-4.N-dihydroxy-5-methyl-benzamidine). The aldehyde is then transformed into the corresponding hydroxyamidine according to literature procedures {see 3-ethyl-4,N-dihydroxy-5-methyl-benzamidine); LC-MS: tp = 0.72 min; [M+lf = 235.09; ^H NMR(CD30D): 5 7.31 (s, 1 H), 7.29 {s, 1 H). 6.10 (m, 1 H), 5.43 (dd, J = 17.0, 1.5 Hz, 1 H), 5.27 (dd, J = 10.3, 1,2 Hz, 1 H), 4.81 (s br, 3H), 4.31 (d, J = 5.6 Hz, 2 H). 2.67 (q, J = 7.6 Hz, 2 H), 2.30 {s, 3 H), 1.23 (t, J = 7.6 Hz, 4 H). 4-Allyloxy-3-chloro-N-hydroxy-5-melhoxy-benzamidine HN o^ HO. O CI The title compound is prepared by allylating commercially available 3-chloro-4-hydroxy-5-methoxybenzaldehyde (see 4-Allyloxy-3-ethyl-N-hydroxy-5-methyl-benzamidine). The aldehyde is then transformed into the corresponding hydroxyamidine according to literature procedures (see 3-ethyl-4,N-dihydroxy-5-methyl-benzamidine); LC-MS: tp = 0.69 min; [M+1]* = 257.26, 4,N-Dihydroxy-3,5-dimethyl-benzamidine The title compound is prepared from commercially available 4-hydroxy-3,5-dimethyl-benzonitrile according to literature procedures (e.g. E. Meyer, A. C. Joussef, H. Gallardo, Synthesis 2003, 899-905); 'H NMR (CD3OD): 5 7.20 (s, 2H), 2.20 (s, 6H). 3-Ethyt-4,N-dihydroxy-5-methyl-benzamidine HN The title compound is prepared from commercially available 2-ethyl-6-methyl-phenol following literature procedures (G. Trapani. A. Latrofa, M. Franco, C. Altomare, E. Sanna, M. Usala, G. Biggio, G. Liso, J. Med. Cham. 41 (1998) 1846-1854; A. K. Chakraborti, G. Kaur, Tetrahedron 55 (1999) 13265-13268; E. Meyer, A. C. Joussef, H. Gallardo, Synthesis 2003, 899-905); LC-MS: tR = 0.55 min; 'H NMR (d^-DMSO): 5 9.25 (s br, 1H), 7.21 (s, 2H), 5.56 (s, 2H), 2.55 (q, J = 7.6 Hz. 2H), 2.15 (s. 3H), 1.10 (t, J = 7.6 Hz, 3H). 3,5-D iethy 1-4, N-dihyd roxy-benza m idi ne HN The title compound is prepared from commercially available 2,6-diethylaniline following literature procedures (G. G. Ecke, J, P. Napolitano, A. H. Filbey, A. J. Kolka, J. Org. Chem. 22 (1957) 639-642; and literature cited for 3-ethyl-4,N-dihydroxy-5-methyl-benzamidine); LC-MS: tp = 60 min; [M+lT = 209.46. 3-Ch lo ro-4, N -d i hyd roxy-5-meth oxy-benza m id i ne OH HN^' "^'■■- ; CI The title compound is prepared from commercially available 3-chloro-4-hydroxy-5-methoxy-benzaldehyde in analogy to the literature cited for 3-ethyl-4,N-dihydroxy-5-methyl-benzamidine; LC-MS: tR = 0.49 min; [M+l]* = 216.96; ^H NMR (Dg-DMSO); SZ.84 (s, 3 H}, 5-79 (s, 2 H), 7.22 (d, J = 1.5 Hz, 1 H), 7.27 (d, J = 1.8 Hz, 1 H), 9.52 (s. 1 H), 9.58 (s br, 1 H), [4-(N-Hydroxycarbamimidoyl)-phenyE]-acetic acid HN a) To a solution of methyl (4-cyanophenyl)acetate (4.00 g, 27.8 mmol) in MeOH (20 mL), hydroxylamine hydrochloride (3,17 g, 45.7 mmol) and NaHCOa (3.84 g, 45.7 mmol) is added. The suspension is stirred at 60''C for 18 h before it is filtered and the filtrate is concentrated. The residue is dissolved in DCM, washed with water followed by brine, dried over MgS04, filtered, concentrated and dried to give methyl [4-(N-hydroxycarbamimidoyl)-phenylj-acetate (3-67 g) as a colouriess oil; LC-MS: tp = 0.50 min, [M+l]* = 209.05. b) A solution of methyl [4-(N-hydroxycarbamimidoyl)-phenyf]-acetate (3.67 g, 17.6 mmol) in 25% aq. HCI (15 mL) is stirred at 65°C for 4 h. The solvent is removed in vacuo and the residue is dried under high vacuum to give [4-(N-hydroxycart)amimidoyl)-phenyl]-acetic acid (3.80 g, presumably as hydrochloride) as a yellow solid; LC-MS: tR = 0.34 min, [M+lf = 195.05. {4_I5.(6.|sobutyl-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-phenyi}-aceticacid COOH The title compound is prepared starting fnsm NJcobntc Bcki 6 and f4-fN-hydroxycarb3mimidoy!Vphenyl]-acetic acid in analogv ic Examcfe '.:. _C-*.^S. -^ = 0.96 min,[IVI+ir = 352.39. 3-[2-Ethyl-4-{N-hydroxycarbamimidoyl)-6-methyl-phenyl]-propionic acid tert-butyl ester NH HO. a) To a solution of 3-ethyi-4-hydroxy-5-methyl-ben2oic acid (80.3 g, 0.446 mol) is DMF (500 mL), KHCO3 (53.5 g. 0.535 mol) followed by benzylbromide (114.3 g, 0.668 moi) is added. The mixture is stirred at 50°C for 18 h before it is cooled to rt, diluted with water (250 mL). and extracted with TBME (2x250 mL). The org. extracts are washed with water, and then concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 19:1 to 9:1 to give 3-ethyl-4-hydroxy-5-methyl-benzoic acid benzyl ester (108.5 g) as a beige solid; 'H NMR (CDCIg): S1.28 (t, J = 7.5 Hz. 3 H), 2.30 {s, 3 H), 2.68 (q, J = 7.8 Hz, 2 H), 5.24 (s, 1 H), 5.37 (s, 2 H), 7.33-7.45 (m, 3 H). 7.45-7.50 (m, 2 H), 7.77 {s, 1 H), 7.79 (s, 1 H). b) To a solution of 3-ethyM-hydroxy-5-methyl-benzoic acid benzyl ester (97.5 g, 0.361 mol) and pyridine (57.1 g, 0.721 mol) in DCM (1000 mL), a solution of trifluoromethanesulfonic anhydride (122.1 g, 0.433 mol) in DCM (100 mL) is added dropwise at 0°C. Alter complete addition, the mixture is stirred at r1 for 2 h before it is washed with 2 N aq. HCI (500 mL) followed by water (500 mL). The org. extract is concentrated and dried to give 3-ethyi-5-methyM-trifluoromethanesulfonyloxy-benzoic acid (140.5 g) as an orange oil; 'H NMR S 1.30 (t, J = 7.5 Hz, 3 H), 2.46 (s, 3 H), 2.83 (q, J = 7.5 Hz. 2 H). 5.39 (s. 2 H), 7.35-7.50 (m. 5H), 7.87(s, 1 H), 7.91 (S, 1 H). c) To a solution of 3-ethyl-5-methyl-4-trifluoromethanesulfonyloxy-benzoic acid (10.0 g, 25 mmol), tert.-butyl acrylate (6.37 g, 50 mmol), NEtj (5.03 g, 50 mmol), and DPPP (0.82 g, 2 mmol) in DMF (100 mL), Pd(0Ac)2 (0.45 g, 2 mmol) is added under a Nj-atmosphere. The mixture is stirred at 115°C for 3 h before is cooled to rt, filtered over a celite pad. The pad is washed with TBME (250 mL) and waer (500 mL) is added to the filtrate. The layers are separated and the org. layer is washed twice with water (2x500 mL), dried over MgS04 and evaporated to dryr^ess. To the crude product is added EtOH (--X mL;, A irkx sLisper^sior forms. The solid materia! is collected, washed with ics-ccHC ErOi- - "C- m_ — zr^ i-2-:er:-butoxycarbony]-vinyl)-3-ethyl-5-methyl-benzoic acid benzyl ester (3.S g) as an off-white solid. d) To a solution of 4-(2-tert-butoxycarbonyl-vinyl)-3-ethyl-5-methyl-benzoic acid benzyl ester (10.0 g, 26 mmol) in THF 100 mL), Pd/C (0.5 g, 20% Pd) is added under nitrogen. The mixture is stirred at rt for 48 h under 1 bar of H;. The catalyst is filtered off over a celite pad and the fiJtrafe is concentrated to dryness to give 4-(2-ten-butoxycarbonyi-ethyiy3- ethyl-5-methyl-benzoic acid (7.64 g) as a white solid; 'H NMR S 1.29 (t, J = 7.5 Hz, 3 H). 1.49 (s, 9 H), 2.36-2.41 (m, 2 H), 2.74 (q, J = 7.5 Hz. 2 H), 2.99-3.05 (m, 2 H), 7.77 (s, 1 H), 7.80 (s, 1 H). e) To a solution of 4-(2-tert-butoxycarbonyl-ethyl)-3-ethyl-5-methyl-benzoic acid (36.0 g, 123 mmol) in isopropanol (400 mL), HOBT (18.3 g. 135 mmol) followed by EDC HCI (27.1 g, 142 mmol) is added. The mixture is stirred at rt for 1 h before aq. ammonia (69 mL of 25% solution) is added. Stirring is continued for 1 h before the mixture is diluted with DCM (500 mL) and washed with half sat, aq, NaHCOs solution (3x400 mL), followed by water (400 mL). The org, extract is dried over MgS04, filtered and concentrated. The crude product is trituated with TBME 8250 mL), The solid material is collected, washed with additional TBME (50 mL) and dried under high vacuum to give 3-(4-carbamoyl-2-ethyl-6- methyl-phenyl)-prcpionic acid tert-butyl ester (31.91 g) as a white solid. f) To a solution of 3-(4-carbamoyl-2-ethyl-6-methyl-phenyl)-^jroptonic acid tert-butyl ester (30.0 g, 103 mmol) and NEta (31.3 g. 309 mmol) in DCM (300 mL), trifluoroacetic anhydride (23.8 g, 113 mmol) is added slowly. The exothermic reaction is kept below 5°C with cooling. After complete addition, the mixture is stirred at rt for 1 h. The mixture is washed twice with water (2x300 mL) and the org. extract is evaporated to dryness to give 3-(4-cyano-2-ethyl-6-methyl-phenyl)-propionic acid tert-butyl ester (28.4 g) as a pale yellow oil; ^H NMR S 1.25 (t, J = 7.5 Hz, 3 H), 1.48 (s, 9 H). 2.32-2.37 (m, 2 H), 2.38 (s, 3 H), 2.70 (q, J= 7.5 Hz, 2 H), 2,95-3.02 (m, 2 H), 7.30 (s, 1 H), 7.34 (s, 1 H). g) A solution of 3-(4-cyano-2-ethyl-6-methyl-phenyl)-propionic acid tert-butyl ester (37.0 g, 135 mmol), hydroxylamine hydrochloride (14.1 g, 203 mmol) and NEta (27.4 g, 271 mmol) in MeOH (400 mL) is heated to reflux for 7 h before it is cooled to rt. The solvent is evaporated and the residue is taken up in isopropylacetate (500 mL) and washed twice with water (500 mL:-. The org. extract is dried over MgSO^, frttefsc. evsporatBd anc dried tc gr/e 3-f2-ethyl^t^;N-^yd^cxyca^t^amirT^idoyl)-6-^^ethyf-pha^vfi-^^^c^f^nK: aaz -^-:-Djr.'; esie' (40.8 g) as a pale yellow solid; ^H NMR S1.26 (t, J = 7.5 Hz, 3 H). 1.49 (s, 9 H). 2.33-2.41 (m, 5 H), 2.66-2.74 (m, 2 H), 2.93-3.01 (m, 2 H), 4.85 (s, 1 H), 7.2S (s, 2 H). 3-[2-Ethyt-4-(N-hydroxycarbamfmidoyl)-6-methyl-phenyl]-propionic acid NH HO. O a) 3-(4-Cyano-2-ethyl-6-methy(-phenyl)-propionic acid ethyl ester is prepared in analogy to 3-(4-cyano-2-ethyl-6-methyl-phenyl)-propionic acid tert-butyl ester; ''H NMR (CDCI3): S 1.21-131 (m, 6 H). 2.37 (s, 3 H). 2.41-2.47 (m. 2 H), 2.69 (q, J = 7.5 Hz, 2 H), 2.99-3.05 (m, 2 H), 4.18 (q, J = 7.0 Hz, 2 H), 7.30 (s, 1 H), 7.33 (s, 1 H). b) A solution of 3-(4-cyano-2-ethyl-6-methyl-phenyl)-prop!onic acid ethyl ester (55.0 g, 224 mmol) in THF (220 mL) and 1 N aq. NaOH solution (220 mL) is stirred at r1 for 2 before it is diluted with water (200 mL) and extracted with DCM (2x200 mL). The aqeous phase is added to 32 % aq. HCI solution (50 mL) at 15-30°C. A precipitate forms. The solid material is collected, washed with water and dried under high vacuum to give 3-(4-cyano-2-ethyl-6-methyl-phenyO-propionic acid (40.87 g) as pate brown crystals; 'H NMR (Ds-DMSO): 51.17 (t, J = 7.5 Hz, 3 H), 2.30-2.39 (m. 5 H). 2.67 (q, J = 7.3 Hz, 2 H), 2.87-2.94 (m, 2 H), 7.47 (s, 2H), 12.30 (s, 1 H). c) To a solution of 3-(4-cyano-2-ethyl-6-methyl-phenyl)-propionic acid (10.0 g, 46.0 mmol) in EtOH (80 mL), NEta (13.97 g, 138.1 mmol) followed by hydroxylamine hydrochloride (6.40 g. 92.1 mmol) is added. The mixure is refluxed for 7 h before it is cooled to rt. The solvent is removed in vacuo. The residue is dissolven in 2 N aq. HCI and the pH is adjusted to 5 by adding 32% aq. NaOH solution. The precipitate that fonns is collected, washed with water and dried under high vacum at 40''C for 18 h to give 3-[2-ethyM-(N-hydroxycarbamimidoyl)-6-methyl-phenyl]-propionic acid (11.7 g) as a beige crystalline powder; LC-MS: IR = 0.60 min, [M+l]* = 251.09. 3-{2-Ethyl-4-E5-{6-isopropoxy-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazal-3-yl]-6-methyl-phenyl}-propionic acid .= N-'x The title compound is prepared from Nicotinic acid 11 and 3-[2-ethyl-4-(N-hydroxycarbamimidoyl)-6-methyl-phenyl]-propionic acid in analogy to Example 13; LC-MS: tR = 1.15 min,[M+ir = 410.10. 3-Ethyl-4-hydroxy-5-methyl-benzoic acid O a) To an ice-cold solution of H2S0^ (150 mL) in water (250 mL) 2-ethyl-6-methylaniline (15.0 g, 111 mmol) is added. The solution is treated with Ice (150 g) before a solution of NaN02 (10.7 g, 155 mmol} in water (150 mL) and ice (50 g) is added dropwise. The mixture is stirred at 0°C for 1 h. 50% aq. H2SO4 (200 mL) is added and stirring is continued at rt for 18 h. The mixture is extracted with DCM, the org. extracts are dried over MgSOd and evaporated. The crude product is purified by CC on silica gel eluting with heptane:EA 9:1 to give 2-ethyl-6-methyl-phenol (8.6 g) as a crimson oil; LC-MS: tR = 0.89 min; ^H NMR (CDCis): 6 7.03-6.95 (m, 2H), 6.80 (t, J =7.6 Hz. 1H), 4.60 (s, 1H), 2.64 (q, J = 7.6 Hz, 2H), 2.25 (s, 3H), 1.24 (t, J = 7.6 Hz, 3H). b) A solution of 2-ethyl-6-methyl-phenol (8.40 g, 61.7 mmol) and hexamethylene tetraamlne (12.97 g, 92.5 mmol) in acetic acid (60 mL) and water (14 mL) is heated to 115°C. The water is distilled off at 117°C and collected with a Dean-Stark apparatus. Then the water separator is replaced by a reflux condensor and the mixture is refluxed for 3 h. The mixture is cooled to rt, diluted with water (100 mL) and extracted with EA. The org. extract is washed with sat. aq. NaHCOs, dried over MgSO^ and evaporated. The remaining solid is dissolved in EA and treated with heptane to initialize crystallisation. The solid material is collected and dried to give 3-ethyl-4-hydroxy-5-methyl-benzaldehyde (3.13 g) as a colourless crystalline powder, ^H NMR (CDCI3): 5 9.83 (s, IN), 7.58-7.53 (m, 2H), 5,30 (s br, 1H), 2.69 (q, J = 7.6 Hz, 2H). 2.32 (s, 3H), 1,28 (t, J = 7.6 Hz, 3H). c) To a solution of 3-ethy!-4-hydrQxy-5-methyl-benzaldehyda C7S.S g, C.45 -noi'. In DMSC-'585 -nL). a solution of NaHiPO. dihydrate (17.3 g, 0.144 rroi ,.' A-HS: '^Z -_ != a-Doec over a period of 13 min. The mixture is stirred at rt an a solution of NaCIO^ i,65,i7 g, 0.577 mol) in water (160 mL) is added while the mixture is cooled with an ice-bath. The mixture is stirred for 1 h before a second portion of NaC(02 (43.44 g, 0.480 mol) in water (100 mL) is added while the temperature is kept between 25 and 40°C with an ice-bath. Th yellow suspension is stirred at rt for 24 h before it is acidified with 32% aq. HCI to pH 2-3. The mixture is extracted with TBME (250 mL), the org. extract is washed with water, and the washings are extracted back with TBME. The solvent of the combined org. extracts is evaporated to give crude 3-ethyl-4-hydroxy-5-methyl-benzoic acid (80.3 g) as a yellow solid. 4-A[lyloxy-3,5-dimethyl-benzoic acid hydrazide O To a solution of 4-aflyJoxy-3,5-dimethyl-benzoic acid (Lit.: see US 3,262,946) (5.26 g, 25.5 mmol) in CHCI3 (75 mL) is added thionylchloride (7.5 mL) and the mixture is heated at reflux for 2 h. The mixture is evaporated and the residue, dissolved in DCM (50 mL), added to a cooled (CC) solution of 1M hydrazine in THF (75 mL) in DCM (250 mL). The mixture Is slowly warmed to rt during 15 h, diluted with ether (150 mL) and washed with 1M aq. HCI {5 x 50 mL). The aq. extracts are washed with ether (50 mL) and the org. phases are discarded. The aq. extracts are basified with 33% aq. KOH and extracted with DCM (5 x 50 mL). The org. extracts are dried (NazS04). filtered and evaporated to give the tifle compound (5.39 g) as a white solid; LC-MS: ts = 0.71 min; [M+lf = 221.20. Methanes u If on ic acid 2,2-dimethyl-(1,3]dioxan-5-yl methyl ester O The tftie compound is prepared following the procedures gr^er- in 3. Xn. K Ssphens G Kirschenheuter, A. ~. Greslin. X. Cheng. J. Senneio. M. Csnar-ec M. ^ Zcre-- A. Cher. S.-A. Kim, H. S. Kim, N. Bischofeerger, G. Cook, K. A. Jacobson, u- fAed. Cnem. 45 ^2002; 5694-5709. Synthesis of Examples Example 1 OH a) A solution of 5-chloro-6-isopropoxy-nicotinic acid (202.9 mg, 0.94 mmol), TBTU (332 mg, 1.04 mmol), Hunig's base (607 mg, 4.70 mmol), and 4-atlyloxy-N-hydroxy-3,5-dimethyt- benzamidine (230 mg, 1.04 mmol) in DCM (7 mL) is stirred at rt for 24 h. The mixture is diluted with ether (150 mL), washed with 1 N aq. HCI (2 x 20 mL), 1 N aq. KHSO4 solution (20 mL) and brine (20 ml), dried over NazS04, filtered and concentrated. The crude product is purified by MPLC on silica gel eluting with a gradient of EA in heptane to give 5- chloro-6-isopropoxy-nicotinJC acid (4-allyloxy-N-hydroxy-3,5-dimethyl-ben2amidine) ester (258 mg) as a white powder; LC-MS:tR = 1.12 min,[M+ir = 418.07. b) A solution of 5-chlorc-6-isopropoxy-nicotinic acid (4-allyloxy-N-hydroxy-3,5-dimethyl-benzamidine) ester (200 mg, 0.48 mmol) in dioxane {6 mL) is stirred at 90°C for 2 days. The solvent is evaporated to give crude 3-[3-(4-allyloxy-3,5-dimethyl-phenyl)-[1,2,4]oxadiazol-5-yl]-5-chloro-6-isopropoxy-pyridine (279 mg); LC-MS: tp = 1.27 min. c) To a solution of 3-[3-(4-9!lyloxy-3,5-dimethyl-phenyl)-[1,2,4]oxadiazol-5-yt]-5-chloro-6-isopropoxy-pyridine (191 mg, 0.48 mmol) in acetone (10 mL) and water (1 mL), NMO (97 mg, 0.72 mmol) followed by OSO4 (12 mg, 0.048 mmol) are added. The mixture is stirred at 45''C for 16 h before it is diluted with 1 N aq. KHS04-solution and extracted with ether (3x50 mL). The combined org. extracts are dried over Na2S04, filtered and concentrated. A sample (15 mg) of the crude product (299 mg) is purified by chromatography on prep. TLC plates with heptane:EA 1:2 to give (RS)-3-{4-[5-(5-chloro-6-isopropoxy-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethyl-phenoxy}-propane-1.2-diol (10.6 mg); LC-MS: tR = 1.06 min, [M+ir = 434.06. Example 2 HO To a solution of crude (RS)-3-{4-[5-(5-chloro-6-isopropoxy-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-2.6-dimethy)-phenoxy}-propane-1,2-diol (265 mg, 0.61 mmo}} in THF (5 mL), Hunig's base (158 mg, 1.22 mmol) followed by methanesulfonylchioride (77 mg, 0.67 mmol) are added at OX. The mixture is stirred at rt for 16 h before 7 M NH3 in MeOH (2 mL) is added. The mixture is stirred at 65''C for 16 h before the solvent is removed in vacuo to give crude (RS)-1-amino-3-{4-[5-(5-chloro-6-isopropoxy-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethyi-phenoxy}-propan-2-ol; LC-MS: \R = 0.92 min, [M+I+CH3CN]* = 474.44. Exampte 3 OH ^ To a solution of (RS)-1-amino-3-{4-[5-(5-chloro-6-isopropoxy-pyr1din-3-yi)-[1,2,4]oxadiazol-3-yl]-2,6-dimethyl-pheTKixy}-propan-2-ol (313 mg. 0.6 mmo!) in DCM (10 mL). glycolic add (95 mg, 1.25 mmol) and Hunig's base (233 mg, 1.8 mmol) are added. The mixture is cooled to 0°C and TBTU (236 mg, 0.74 mmol) is added. The mixture Is stirred at 0°C for 1 h. then at rt for 16 h before it is diluted with EA (250 mL), washed with 1 N aq. NaOH solution (3x25 mL), 1 N aq. KHSO4 (25 mL) and brine (25 mL), dried over Na2S04. filtered and concentrated. The crude product is purified by prep. HPLC to give N-((RS)-3-{4-[5-(5-chloro-6-isopropoxy-pyridin-3-yl)-[1,2,4]oxadia2ol-3-yl]-2,6-dimethyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide (42 mg) as a white powder; LC-MS: tp = 1.06 min; [M+1]* = 491.48; ^H NMR (CD30D) 6 1.45 (d, J = 6.3 Hz, 6 H). 2.38 (s. 6 H), 3.47 (dd. J = 13.6. 7.3 Hz, 1 H), 3.66 (dd, J = 13,6, 4.5 Hz, 1 H), 3.87 (m, 2 H), 4.04 (s, 2 H), 4.14 (m, 1 H), 5.52 (m, 1 H), 7.78 (s, 2 H), 8.43 (s, 1 H), 8,85 (s, 1 H) Example 4 N- 0~ ■N = N' (RS)-3-{4-[5-(6-lsobutyl-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazoi-3-yl]-2,6-dimethyt-phenoxy}-propane-1,2-drol is prepared in analogy to Example 1; LC-MS: tn = 0.92 min, [M+1]^ = 412.21. Example 5 OH 2-Hydroxy-N-((RS)-2-hydroxy-3-{4-[5-(6HSObutyl-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-ylJ-2,6-dimethyl-phenoxy}-propyl)-acetamide is prepared in analogy to Example 2 and 3; LC-MS: tR = 0.89 min, [M+lf = 469.57. Example 6 CRS)-3-{2-Ethyl-4-[5-(6-lsobutyl-5-methyl-pyridin'3-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-propane-1,2-dlal is prepared in analogy to Example 1; LC-MS: t^ = 0.95 min, [M+1]* = 426.14. Example 7 ff?S)-1-Amfno-3-{2-ethyi-4-[5-(6-isobutyl-5-methyl-pyridiri-3-y:H'.2.4]cxaSaz3^3-j;'>o-m9thyi-phenoxy]-propa.n-2-oi is prepared in analogy to Exa^iDie 2: _3-M5- "^ = Z 52 rr:ir; [M+ir = 425.17. Example 8 N-((RS)-3-{2-Ethyl-4-[5-(6-isobutyl-5-methyl-pyridin-3-yl}-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-2-hydroxy-propyi)-2-hydroxy-acetamide is prepared in analogy to Example 3; LC-MS: tp = 0,91 min,[M+ir= 483.21. Example 9 (RS)-3-{2-Ethyl-4-[5-(5-isobutyl-6-methyl-pyridin-3-yl)-[1,2,4Joxadiazol-3-yl]-6-methyl-phenoxy}-propane-1,2-diol is prepared in analogy to Example 1; LC-MS; t^ = 0.96 min, [M+1]* = 426.12. Example 10 (/?S)-3-{2,6-Dimethyl-4-[5-{5-methyl-6-propyl-pyridin-3-yl)-[1,2.4]oxadiazol-3-yn-phenoxy}-propane-1,2-diol is prepared in analogy to Example 1; LC-MS: XR = 0.87 min, [M+1]' 398.54. Example 11 N- O- N N' '0' HO 'Oh (/?S)-3-{2-Ethyl-6-methyW-[5-(5-methyl-6-propyl-pyridin-3-yl)-[1,2.4]oxadia2ol-3-y|]-phenoxy}-propane-1.2-diol is prepared in analogy to Example 1; LC-MS; IR = 0.91 min, [M+ir = 412.56, Example 12 (;?S)-3-{4-[5-(5.6-Diisobutyl-pyndin-3-yiH1,2,4]oxadiazo)-3-yl]-2,6-Ter:Cx-^^^ -s preparea in analogy to Example 14 using bromoethanol as rse afr/THuTc sciert. _:;-WS. u = 1.01 min;[M+ir = 382.17; ^HNMR(CDCl3) 6 1.22-1.45 (m. 9 H). 2.42 (S. 3 H). 2.72-2.87 (m, 4 H), 2.96 (q, J = 7.5 Hz, 2 H), 4.00 (m, 5 H), 7.89 (s. 1 H). 7.90 (s. 1 H}, 6.24 (s. 1 H>, 9.21 (8, 1 H). Example 17 a) To a solution of 4-[5-(5,6-diethyl-pyridin-3'yl)-[1.2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenol (150 mg, 0.445 mmol) in isopropanol (10 mL) and 3 N aq. NaOH (3 mL), epichlorhydrine (164 mg, 1.78 mmoi) is added. The mixture is stirred at rt for 20 h. The mixture is diluted with EA and washed with sat. aq. NaHCOa solution. The org. extract is dried over MgS04, filtered and evaporated. The crude product is purified by chromatography on prep. TLC plates with EA-heptane to give (RS)-2,3-diethyl-5-[3-(3-ethyl-5-methyl-4-oxiranylmBthoxy-phenytH1,2,4]oxadiazol-5-yl]-pyridine (92 mg) as an oil. b) (RS)-2,3-Diethyl-5-[3-(3-ethyl-5-methyl-4-oxiranylmethoxy-phenyl)-(1,2,4]oxadiazol-5-yl]-pyridine (92 mg) is dissolved in 7N NH3 in MeOH (20 mL) and heated in a screw cap bottle at 60°C for 15 h. The mixture is evaporated to give crude (RS)-1-amino-3-{4-[5-(5,6-diethyl-pyridin-3-yl)-[1,2,4]oxacfezol-3-yl]-2-ethyl-6-methyl-phenoxy}-propan-2-ol (99 mg); LC-MS: IR = 0.80 min, [M+l]^ ^ 411.09, Example 18 To a solution of (/?S)-1-amino-3-{4-[5-(5,6-diethyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propan-2-ol (99 mg, 0.24 mmol), glycolic acid (18.5 mg, 0.244 mmol) and Hunig's base (78 mg, 0.61 mmol) in DCM (5 mL) is added PyBOP (126.7 mg, 0.24 mmol) and the mixture is stirred at rt for 30 min. The mixture is diluted with EA, washed with sat. aq. NaHCOg solution, dried over MgSO.^, filtered and concentrated- The crude product is purified by chromatography on prep. TLC plates eluting with DCMrMeOH 55 10:1 to gh/e N-((RS)-3-;;4-[5-(5.6-diethy!-pyridin-3-yl)-[1,2,4Joxadiazo^3r->'';]-2-p-lenoxy>-2-.nydroxy-prapy:'-2-hydroxy-3cetamide (90 ,Tig'' as ar- z-^'r ^C->J'-S [M+l]^ =469.25. Example 19 2-Ethyl-4-I5-(6-ethyl-5-isobutyl-pyridin-3-yl)-[1,2,4]oxadiazo5-3-y3]-6-mettiyl-phenoi prepared in analogy to Example 13; LC-MS: tp = 1,09 min, [M+lf = 366.19- fS Example 20 '^O'^ Y OH 8H (S)-3-{2-Ethyl-4-[5-(6-ethy!-5-isobutyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-propane-1,2-diol is prepared in analogy to Example 14; LC-MS: tp = 1.00 min, [M+l]"" = 440.20. Example 21 (S)-2-{2-Ethyl-4-[5-(6-ethyl-5-isobutyl-pyridin-3-ylH1,2,4]oxadiazol-3-yf]-6-methyl-phenoxy}- ethanol is prepared in analogy to Example 16; LC-MS: IR = 1.08 min, [M+lf = 410.15. Example 22 -,=thvi iRSV1-Amino-342-ethyi-4-[5-f6-ethy!-5HSObutyl-pyridtn-3-yiH1.Z4:cxaaiazD>-5-yr:-6- etnyi-pn2nox\'hpropa^'--:-Dt 1= prepared in analogy to Examoie '''■ ^C-M3: -_= = : S5 ~,.-[M+lf =439.17, Example 23 N-((RS)-3-{2-Ethyl-4-[5-(6-ethy|-5-isobutyi-pyridin-3-y!H1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-2-hydrDxy-propyl)-2-hydroxy-acetamide is prepared in analogy to Example II LC-MS: tR = 0.95 min, [M+lf s: 497.17. Example 24 4-[5-(6-lsobutyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yll-2,6-dimethyi-phenol is prepared in analogy to Example 13; LC-MS: tp = 1.04 min, [M+lf = 324.36. Example 25 (RS)-1-Amino-3-{4-[5-{6HSobutyl-pyridin-3-yl)-[1,2,4]oxadiazof-3-yI]-2,6-dimelhyl-phenoxy}-propan-2-ol is prepared in analogy to Example 17; LC-MS: tp = 0.8 min. Example 26 OH 2-Hydroxy-N-{(/?S)-2-hydroxy-3-f445-(6-isobutyl^pyridin-3-yiH1.2.4}cxac:iazDi-^ri-2.a-~irnetny!-ph=noxy}-propy-:-3cetarnide is prepared in analogy tc Exa'-^c^e 'S .Z-^/S -^ = 0.89 min,[M+1]^ = 455.48- Example 27 CI OH (RS)-3-{2-Chloro-4-[5-(6-isobutyl-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-6-methoxy-phenoxy}-propane-1,2-diol is prepared in analogy to Example 1; LC-MS: tp = 0.94 min, [M+ir = 448.21. Example 28 N—; a) To a solution of 6-isobutyl-5-methyl-nicotinic acid hydrochloride (50 mg, 0.22 mmol), DIPEA (0.12 mL, 0.7 mmol) and TBTU (97 mg, 0.30 mmol) in DCM (5 mL) is added at 0°C 4-allyloxy-3,5-dimethyl-benzoic acid hydrazide (50.6 mg, 0.23 mmol) and the mixture is stirred at O^C for 4 h. The mixture is diluted with EA (15 mL) and washed with 1M aq. NaH2P04 (5 mL), 1M aq. NaOH (5 mL) and water (5 mL). The org. phase is dried (MgSO^). filtered and evaporated to provide 6-isobutyl-5-methyl-nicotinic add N"-(4-allyloxy-3,5-dimethyl-benzoyl)-hydrazide (85 mg); LC-MS: tR = 0.81 min, [M+l]* = 396.20. b) A solution of 6-isobutyl-5-methyl-nicotinic acid N'-(4-allyloxy-3,5-dimethyl-benzoyl)-hydrazide (89 mg, 0.224 mmol) and Burgess reagent (162 mg, 0.68 mmol) in THF (4 mL) is heated in a microwave oven at HO^C for 6 min. The mixture is diluted with EA (15 mL) and washed with 1M aq. NaH2p04 (5 mL), 1M aq. NaOH (5 mL) and water (5 mL). The org. phase is dried (MgS04), filtered and evaporated to provide crude 5-[5-(4-allyloxy-3,5-dimethyl-phenyl)-[1,3,4]oxadiazol-2-yl]-2-isobuty!-3-methyl-pyridine (80 mg); LC-MS: XR = 1.07 min, IM+ir = 378.3. 58 ci (RSV3^4-[5-{6-lsobutyl-5-methy!-pyridin-3-ylHi,3,4jcx3ciiazD!-2-j-^>Ze-3i~^tn/:.- onencxy>-DroDane-1,2-db' is prepared from 5-[5-'4-2)r,'K:rv-3.5-irTe-—^.---^n-/i_ [1,3,4]oxadiazoi-2-yl]-2-isobuty!-3-methyl-pyridine in analogy to Example 1: LC-MS: IR = 0.83 min; [M+lf = 412.23: 'H NMR (Ds-DMSO) 5 0,94 (d, J = 6.5 Hz. 6 H). 2-1S (hept. J = 6.5 HZ, 1 H), 2,36 (s, 6 H), 2.42 (s, 3 H), 2.73 (d, J = 7.3 Hz, 2 H), 3.50 (t. J = 5.5 Hz, 2 H), 3.76 {m, 1 H), 3.84 {m, 1 H), 3.89 (m, 1 H), 4.65 (t, J = 5.5 Hz, 1 H), 4.97 {d, J = 5.0 Hz, 1 H), 7.84 (s, 2 H), 8,24 (d, J =1.0 Hz, 1 H), 9,05 (d, J = 1.5 Hz, 1 H}. Example 29 Starting from nicotinic acid 2, {RS)-3-{4-[5-(5-isobutyl-6-methyl-pyridin-3-yi)-[1.2,4]oxadiazot-3-yl]-2,6-dimethyl-phenDxy}-propane-1,2-diol is prepared in analogy to Example 1; LC-MS: t^ = 0.93 min; [M+lf = 412.18. Examples 30 to 34 rac The following examples are prepared in analogy to Example 1 starting from nicotinic acid 6. Example Ra Rb Re LC-MS tRrminl [M+Hl* 30 H H H 0.83 384.50 31 CH3 H H 0.86 398.48 32 H OCH3 H 0.75 414.20 33 H Br H 0.93 462.20 34 H CH3 CI 0.95 432.26 Example 34 'H NMRi"CL>'3b): d"1.01 :- J=5.S Hz, 5 H;,2,13-2,31 (m. 1 H; 2.^5 s 3-' ^^t s :■-2.80 {d. J= 7,3 Hz, 2 H), 3,82-3,96 fm, 2 H), 4,06-4.13 {m, 2 H), 4,15^,23 (m, 1 H}, 7,95 (d, J = 0.8 Hz, 1 H), 8,09 (d, J =1,5 Hz, 1 H), 8.21 {s, 1 H), 9,19(s. 1 H). Examples 35 to 39 rac The following examples are prepared from previous examples in analogy to Example 2. Example Ra Rb Re LC-MS tRrminl FM+Hf 35 CH3 H H 0.78 397.07 36 H OCH3 H 0.68 413.17 37 H CH3 CI 0.82 431.49 38 H OCH3 Ci 0.81 447.15 39 H CH3 CH3 Examples 40 to 43 rac The following examples are prepared from previous examples in analogy to Example 3. Example Ra Rb Re LC-MS tRTminl [M+HJ* 40 CH3 H H 0.84 455.45 41 H OCH3 H 0.73 471.22 42 H CH3 CI 0.90 489.20 43 H OCH3 CI 0.90 505.16 Example 40 "H NMR^CDCU): .^1.01 :2. j^6.5Hz. 6 H).2.17-2.30(m '.r...2.A^ = 2-:.Z5= s 3H 2.80(d, J= 7.3 Hz, 2 H), 3.13-3,19 (m, 1 H), 3.47-3.56 (m, 1 H), 3.72-3.S0 im, i H), 3.99-4.08 (m, 2 H). 4.17-4.24 (m. 3 H). 6.85-6.90 (m, 2 H), 7.08 (t br. .J = 5.5 Hz, 1 H). 8.06 (d, J = 8.3 Hz, 1 H). 8.21 (s. 1 H), 9.20 {s, 1 H) Example 44 (/?S)-1-{2-Chloro-4-[5-(6-isobutyl-5-methyl-pyrid(n-3-yl)-[1,2,4]oxadiazo[-3-ylj-6-methoxy-phenoxy}-3-(2-hydroxy-ethylamino)-propan-2-ol is prepared from Example 27 in analogy to Example 2 by reacting the methansulfonylated intermediate with ethanolamine, LC-MS: IR = 0.82min, (M+lf = 491.06; 'H NMR (CDCI3): oxy-azetid"iny!)-2-acetyl, l-(2- carboxy-pyrrolidinyI}-2-acetyi, 1 -(3-carboxy-pyrTolidinyJ)-2-acety). 1 -(3-carboxy-azetidinyl)- 3-propionyl, 1 -(2-carboxy-pyrrolidinyl)-3-propjonyl, 1 -(3-carboxy-pyrrolidinyl>-3-propiony}, -(CH2)nCH(OH)-CH2-NR^^R", hydroxy, hydroxy-Cs-s-alkoxy, di-{hydroxy-C,^-a[ky])-Ci^- alkoxy, 2,3-dihydroxy-propoxy, 2-hydroxy-3-methoxy-propoxy, -OCH2-(CH2)rr,-NR^''R^^, 2- [(azetidine-3-carboxylic acid)-1-yl]-ethoxy, 2-[{azetidine-3-carboxylic acid Ci_5-a)kylester)-l- yl]-ethoxy, 2-[(pyrroiidine-3-carboxylic acid)-1-yl]-ethoxy, 2-[(pyrrolidine-3-carboxylic acid C,.5-alkylester)-1-y[]-ethoxy, -OCH2-CH(OH)-CH2-NR^'R^^, 3-[(azetidine-3-carboxylic acid)- 1-yl]-2-hydroxypropoxy, 3-[{a2etidine-3-carboxyiic acid C,_5-alkylester)-1-yl]-2- hydroxypropoxy, 2-hydroxy-3-[(pyrrolidine-3-carboxylic acid)-1-yl]-propaxy, 2-hydroxy-3-[(pyrroiidine-3-carboxylic acid Ci-5-aikylester)-1-yl]-propoxy, 2-hydroxy-3-[(pyrrolidine-2-carboxylic acid)-1-yl]-propoxy, 2-hydroxy-3-[(pyrrolidine-2-carboxylic acid Ci.5-alkylester)-1-yl]-propoxy. -OCH2-(CH2)^-NHS02R", -OCH2-CH(OH}-CH2-NHS02R^^ -OCH2-(CH2)r.-NHCOR", -OCH2-CH(OH)-CH2-NHCOR^; R^^ represents hydrogen, Ci.3-alkyl, 2-hydroxyethyl, 2'hydroxy-1-hydroxymethyl-ethyl, 2,3-di hydroxy propyl, carboxymethyl. 1-(Ci.5-alkylcarboxy)methyl, 2-carboxy ethyl, or 2-(Ci.5-alky!carboxy)ethyt; R" represents hydrogen, methyl, or ethyl; R" represents Ci.3-alkyl, methylamino, ethylamino, ordimethylamino; R" represents hydroxymethyl, hydroxyethyl, aminomethyl, methylanninomethyl, dimethylaminomethyl, aminoethyl, 2-methylamino-ethyl, or 2-dimethyla mi no-ethyl; k represents the integer 1, 2, or 3; m represents the integer 1 or 2; n represents 0, 1, or 2; and R® represents hydrogen, Cn-alkyl or halogen; and a salt of such a compound. 6- A compound according to any one of claims 1 re 4. wh&sir R'' represents C-_--alkyj; and a sait of such a compound. 7, A compound according to any one of claims 1 to 6, wherein R^ represents C-_5-alkyl: and a salt of such a compound. 8. A compound according to any one of claims 1 to 6, wherein R^ represents n-propyl, or /so-butyl; and a salt of such a compound- 9- A compound according to any one of claims 1 to 6, wherein R^ represents Ci-4-alkoxy; and a salt of such a compound. 10. A compound according to any one of claims 1 to 9, wherein R^ represents hydrogen; and a salt of such a compound. 11. A compound according to any one of claims 1 to 9, wherein R^ represents hydrogen; and R"* represents C,^-alkyl, or C,_^-alkoxy; and R* represents Cj-4-alkyl, or halogen; and a salt of such a compound. 12. A compound according to any one of claims 1 to 9, wherein R^ represents hydrogen, R** represents Ci-3-alkyl, or methoxy, and R^ represents methyl, ethyl, or halogen; and a salt of such a compound. 13. A compound according to any one of claims 1 to 12, wherein R* represents 2,3-dihydroxypropyl, di-(hydroxy-Ci^-alkyl)-C,^-alkyl, -CH2-(CH2)k-NHS02R^^ -(CH2)nCH(0H)-CHs-NHSOaR^l -CH^-iCH^X-NHCOR^, -{CH2)„CH{OH)-CH2-NHCOR^, -CH2-{CH2V CONR^^R". -C0-NHR^\ -{CH2)nCH(OH)-CH2-NR^'R^, hydroxy. hydroxy-C^s-alkoxy, di-(hydroxy-CM-alkyl)-Ci.4-a(koxy, 2,3-dihydroxy-pfDpoxy, 2-hydroxy-3-methoxy-propoxy, -OCH2-{CH2)r.-NR^^R", -0CH2-CH(0H)-CH2-NR=^R", -OCHS-CCHJ^NHSOSR", -OCHJ-CH(0H)-CH2-NHS02R", -OCH2-(CH2)m-NHCOR^, or -0CH2-CH(OH)-CHrNHC0R^; and a salt of such a compound. 14. A compound according to any one of claims 1 to 12, wherein R^ represents 2,3-dihydroxypropyl, -CHz-(CH2)k-NR^^R^^ -CH2-(CH2)K-NHCOR^, -(CH2)nCH(OH)-CH2-NHCOR^, -CH^-(CH2)n-C0NR^'R^^ -CO-NHR^\ -(CH2)aCH(OH)-CH2-NR^'R", hydroxy-C?-s-alkoxy, di-{hydroxy-Ci-,-alkyl)-Ci^-alkoxy, 2,3-dihydroxy-propoxy, 2-hydroxy-3-methoxy- propoxy. -OCH2-{CH2)n,-NR^'R-l -OCH2-CH(OH)-CHz*MR^"R^. OCSHCH^K-N'^COR", or -OCH^H{OH)-CH;-NHCOR^; and a saft of sucn = CC-I^DOUPC. 15. A compound according to any one of claims 1 to 12, wherein R^ represents hydroxy-C2,5-alkoxy, di-(hydroxy-C,^-alkyl)-Ci-4-alkoxy, 2,3-dihydroxy-propoxy, -OCH2-{CH2)m-NR^^R^^ -OCH2-CH(OH)-CH2-NR^'R", -OCH2-(CH2U-NHCOR", or -OCH2-CH(OH)-CH2' NHCOR"; and a salt of such a compound. 16. A compound according to any one of claims 1 to 12, wherein R^ represents 3-hydroxy-2-hydroxymethyl-propoxy, 2,3-dihydroxy-propoxy. or -OCH2-CH{OH)-CH2-NHCOR^; and a salt of such a compound, 17. A compound according to claim 1 selected from the group consisting of: 3-{4-[5-(5-Chloro-6-isopropoxy-pyridin-3-yl}-[1,2,4]oxadiazol-3-yl]-2,6-dimethyl-phenoxy}-propane-1,2-diol; N-(3-{4-[5-{5-Chloro-6-isopropoxy-pyridin-3-yiH1.2.4]oxadiazol-3-yl]-2,6-dimethyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide; 3-{4-[5-(6-lsobutyl-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethyl"phenoxy}-propane-1,2-diol; 2-Hydroxy-N-(2-hydroxy-3-{4-[5-(6-isobutyl-5-methyl-pyndin-3-yl)-[1,2,4]oxadiaZOl-3-yl]-2,6-dimethyl-phenoxy}-propyl)-acetamide; N-{3-{2-Ethy)-4-[5-(6-isobutyl-5-methyl-pyrJdin-3-ylH1>2.4]oxadiazol-3-yl]-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide; 3-{4-[5-(5,6-Diisobutyl-pyridin-3-ylH''.2,4]oxadiazol-3-yt]-2,6-dimethyl-phenoxy}-propane- 1,2-diol; N-(3-{4-[5-{5,6-Diethyl-pyridin-3-yi)-[1,2,4]oxadiazol-3-ylJ-2-ethyl-6-methyl-phenoxy}-2-hyd roxy-propy! )-2-hydroxy-aceta m ide; 2-Hydroxy-N-(2-hydroxy-3-{4-[5-(6-isobutyl-5-methyl-pyridin-3-ylH1,2,4]oxadiazol-3-yl]-3- methyl-phenoxy}-propyl)-acetamide; N-(3-{2-Chloro-4-i5-{6-isobutyl-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl- phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide; N-{3-{2-Chloro-4-[5-{6-isobutyl-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-6-methoxy-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide; N-{(R)-3-{2-Ethyl-4-[5-(6-isobutyl-5-methyl-pyridin-3-ylH1,2,4]oxadiazol-3-yl]-6-methyl- phenoxy}-2-h yd roxy-p ropyi)-2-hyd roxy-acetam ide; 77 N-((S)-3-{2-Ethyl^-E3-(6-isobutyl-5-niethyl'pyrid"rri-3-yiH'i2.4}GX3diazo;-5-yi]-5-rrrethyt- phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide: N-((S)-3-{2-Ethyl^-[5-(6-isobutyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yi]-6-methy(-phenoxy}-2- hydroxy-propyI)-2-hydroxy-acetamide; (S)-3-{2-Ethy(-4-[5-(5-ethyl-6-isobutyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}- propane-1,2-diol; N-(3-{2-Ethyl-4-[5-(5-ethyl-6-isobutyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}- 2-hydroxy-propyl)-2-hydroxy-acetamide; (R}-3-{2-EthyM-[5-(6'isopropoxy-5-methyl-pyridin-3-ylH1.2,4]oxadiazol-3-y[]-6-methyl- phenoxy}-propane-1,2-drol; (S)-3-{2-Ethy)-4-[5-(6-isopropoxy-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-y!]-6-methyl- phenoxy}-propane-1,2-diol; N-{(R)-3-{2-Ethyl-4-[5-(6-isopropoxy-5-methyi-pyridin-3-y))-[1,2,4]oxadiazol-3-y!]-6-methyl- phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide; N-({S)-3-[2-Ethyl-4-[5-(6-isopropoxy-5-methyl-pyrid)n-3-yl)-[1,2,4]oxadiazot-3-yl]-6-methyl- phenoxy}-2-hydroxy-propyO-2-hydroxy-acetamide; 3-{2-Ethyl-4-[5-(6-isopropoxy-5-methyl-pyridin-3-yi)-[1,2,4]oxadiazol-3-yJj-6-methyl-phenyl}- N-(2-hydroxy-ethyl)-propionamlde; (R)-3-{2-EthyM-[3-(6-isopropoxy-5-methyl-pyndin-3-yl)'[1,2,4]oxadiazol-5-yl]-6-methyl- phenoxy}-propane-1,2-diol; (S)-3-{2-Ethyl-4-[3-(6-isopropoxy-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-6-methyl- phenoxy}-propane-1,2-diol; and 3-{2-Ethyl-4-{5-(6-isopropoxy-5-methyl-pyridin-3-yl)-[1.2,4]oxadiazoI-3-yl]-6-methyl-phenyl}- propionic acid; and a salt of such a compound. 18, A compound of Formula (II) CH2-(CH2)n-COOH Formula (II) wherein A, R\ R^, and n are as defined in claim 1; R' represents hydrogen; R'* represents Ci^-alkyl, or Ci^-alkoxy; and R^ represents Ci^-alkyl. or halogen. 19. A pharmaceutical composition comprising a compoijr>d accorair>c :c any one o^ ciaims 1 to 17, or a pharmaceuticaiiy acceptable salt thereof, and a pharmaceuticaily acceptabie carrier. 20. A compound according to any one of claims 1 to 17, or a pharmaceuticaily acceptabie sait thereof, or a pharmaceutical composition according to claim 19, for use as a medicament. 21. Use of a compound according to any one of claims 1 to 17, or a pharmaceuticaily acceptable salt thereof, for the preparation of a pharmaceutical composition for the prevention or treatment of diseases or disorders associated with an activated immune system. 22. The use according to claim 21 for the prevention or treatment of diseases or disorders selected from the group consisting of rejection of transplanted organs such as kidney, liver, heart, lung, pancreas, cornea, and skin; graft-versus-host diseases brought about by stem cell transplantation; autoimmune syndromes including rheumatoid arthritis, multiple sclerosis, inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, psoriasis, psoriatic arthritis, thyroiditis such as Hashimoto's thyroiditis, uveo-retinitis; atopic diseases such as rhinitis, conjunctivitis, dermatitis; asthma; type I diabetes; post-infectious autoimmune diseases including rheumatic fever and post-infectious glomerulonephritis; solid cancers and tumor metastasis. 23. Use of a compound according to any one of claims 1 to 17, or a pharmaceuticaiiy acceptable salt thereof, for the preparation of a pharmaceutical composition for use in combination with one or several agents selected from the group consisting of immunosuppressants, corticosteroids, NSAID's, cytotoxic drugs, adhesion molecule inhibitors, cytokines, cytokine inhibitors, cytokine receptor antagonists and recombinant cytokine receptors, for the prevention or treatment of diseases or disorders associated with