| 摘要 |
Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided including compounds which modulate subtype 1 of the S1P receptor, having the following structural formula:wherein a dashed line signifies that a single bond or a double bond can be present, provided that there are two double bonds and three single bonds in the ring comprising A, Aand A; A, Aand Aeach independently is C or S or N; provided that one of A, Aand Ais S; Ris di-substituted phenyl where the phenyl substituents are each independently selected from the group consisting of halo, nitro, cyano, perfluromethyl, fluorinated methyl and C-alkoxy; provided that phenyl is para-substituted with C-alkoxy; Riswherein a wavy line indicates a point of attachment; X is NR'R" or -OR'"; R' is H, C-alkyl, n-hydroxy C-alkyl, -SO-Ror -CO-R; R" is H, -SO-R, C-alkyl optionally substituted with 1 or more R, or a ring moiety optionally substituted with R, wherein such ring moiety is piperidinyl, cyclohexyl, morpholinyl, thiazolyl, pyrazolyl, pyrrolidinyl, imidazolyl or phenyl; R'" is H, C-alkyl or -CO-R; or R' and R" taken together with the nitrogen atom to which they are bound form a 4-, 5- or 6-membered saturated heterocyclic ring containing 0 or 1 additional heteroatom, where such additional heteroatom is O or N, wherein such heterocycle is optionally singly or multiply substituted with substituents independently selected from the group consisting of -OH, oxo, -NH, n-hydroxy- C-alkyl, -COOH, -(CH)-COOH, -(CH)-COOR, -N(RR) and -(CH)-CO-N(RR); each Ris independently C-alkyl or H; each Ris independently H, halo, OH, oxo, =NH, NH, -COOH, F, -NHR, -N(RR), -SO-R, -SO-N(RR), -N(R)-SO-R, -COOR, -OCO-R, -CO-N(RR), -N(R)-COR, C-alkyl, C-alkoxy and a ring moiety optionally substituted with R, wherein such ring moiety is piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, pyrazolyl, imidazolyl, benzimidazolyl, azetidinyl, cyclobutinyl or phenyl; each Ris independently R, C-alkyl, C-cycloalkyl or C-alkyl optionally substituted with 1 or more R; each Ris independently halo, OH, -NH, -NHR, -N(RR), -COOH, -COOR, - NHCO-R; each Ris independently C-alkyl or H, or two Rtaken together with the nitrogen atom to which they are bound form a 4-, 5- or 6-membered saturated heterocyclic ring containing 0 or 1 additional heteroatom, where such additional heteroatom is O or N, wherein such heterocycle is optionally substituted with -OH, -NH, -N(RR), n-hydroxy C-alkyl, -(CH)-COOH, -(CH)-COOR; each m is independently 0, 1, 2 or 3. Provided is the use for the treatment or prevention of diseases, malconditions and disorders, i.e. multiple sclerosis, for which modulation of the sphingosine 1 phosphate receptor is medically indicated. |
