Selective heterocyclic sphingosine 1 phosphate receptor modulators

A compound of Formula (I) or a pharmaceutically acceptable salt, ester, prodrug, homolog, tautomer, stereoisomer, or hydrate, or solvate thereof:

• 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 A1, A2, and A3;
• A1, A2, and A3 each independently is CH or S or N;
• provided that one of A1, A2, and A3 is S;
• R1 is di-substituted phenyl or di-substituted pyridinyl where the phenyl and pyridinyl substituents are each independently selected from the group consisting of halo, nitro, cyano, perfluromethyl, fluorinated methyl, and C1-4-alkoxy;
• provided that if R1 is di-substituted phenyl, such phenyl is para-substituted with C1-4-alkoxy;
• R2 is
• wherein a wavy line indicates a point of attachment;
• X is —NR′R″ or —OR′″;
• R′ is H, C1-4 alkyl, n-hydroxy C1-4 alkyl, —SO2—R3, or —CO—R3;
• R″ is H, —SO2—R5 , C1-4 alkyl optionally substituted with 1 or more R4, or a ring moiety optionally substituted with R6 wherein such ring moiety is piperidinyl, cyclohexyl, morpholinyl, thiazolyl, pyrazolyl, pyrrolidinyl, imidazolyl, or phenyl;
• R′″ is H, C1-4 alkyl, or —CO—R3
• 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 heteroatoms 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, —NH2, n-hydroxy-C1-4 alkyl, —COOH, —(CH2)m—COOH, —(CH2)m—COOR3, —N(R3R3), and —(CH2)m—CO—N(R7R7);
• each R3 is independently C1-4 alkyl or H;
• each R4 is independently H, halo, OH, oxo, ═NH, NH2, —COOH, F, —NHR3, —N(R7R7), —SO2—R3, —SO2—N(R7R7), —N(R3)—SO2—R3, —COOR3, —OCO—R3, —CO—N(R7R7), —N(R3)—COR3, C1-3 alkyl, C1-3 alkoxy, and a ring moiety optionally substituted with R6 wherein such ring moiety is piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, pyrazolyl, imidazolyl, benzimidazolyl, azetidinyl, cyclobutinyl, or phenyl;
• each R5 is independently R4, C1-4 alkyl, C3-6 cycloalkyl, or C1-4 alkyl optionally substituted with 1 or more R4;
• each R6 is independently halo, OH, —NH2, —NHR3, —N(R3R3), —COOH, —COOR3, —NHCO—R3, each R7 is independently C1-4 alkyl or H, or two R7 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 heteroatoms where such additional heteroatom is O or N wherein such heterocycle is optionally substituted with —OH, —NH2, —N(R3R3), n-hydroxy C1-4 alkyl, —(CH2)m—COOH, or —(CH2)m—COOR3;
• each m is independently 0, 1, 2, or 3.