| 主权项 |
1. A method of treating a disorder associated with sphingosine-1-phosphate 1 (S1P1) receptor modulation, the method comprising administering to a mammal in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I: wherein: R1 is hydrogen, halogen or C1-6 alkyl; R2 is CR3 or N; R3 is hydrogen, halogen, O(C1-6 alkyl), S(C1-6 alkyl), cyano, aldehyde, heterocycle, C1-6 alkyl or hydroxyl; R4 is CR5 or N; R5 is hydrogen, halogen, hydroxyl or non-substituted C1-6 alkyl; R6 is CR7 or N; R7 is —NHR12, —S(O)2R14, —C(O)NHR16, —OR17, hydrogen, halogen, phosphonic acid, boronic acid, —CH2—OH, —CH2—S(O)2CH3, —(CH2)a—NH—(CH2)b—Oc—P(O)(OH)2, —(CH2)d—C(NH2)(CH2OH)(CH2—O—P(O)(OH)2), —(CH2)e—C(NH2)(CH3)(CH2—O—P(O)(OH)2) or —(CH2)fNH—(CH2)g—SO3H; a is 1 or 2; b is 2 or 3; c is 0 or 1; d is 0 or 1; e is 0 or 1; f is 0 or 1; g is 2 or 3; R8 is CR9 or N; R9 is hydrogen, halogen, non-substituted C1-6 alkyl or hydroxyl; R10 is CR11 or N; R11 is hydrogen, halogen or C1-6 alkyl; R12 is hydrogen, C1-6 alkyl, —C(O)R13, —S(O)2(C1-3 alkyl) or heterocycle; R13 is amino or C1-6 alkyl; R14 is C1-4 alkyl, NHR15 or hydroxyl; R15 is hydrogen or C1-6 alkyl; R16 is hydrogen or C1-6 alkyl; R17 is hydrogen, C1-6 alkyl or —S(O)2(C1-3 alkyl); R18 is C2-4 alkyl or —OC2-4 alkyl; R19 is hydrogen, halogen or C1-6 alkyl; R20 is hydrogen, halogen or C1-6 alkyl; and R21 is —C1-4 alkyl; wherein each said alkyl is optionally substituted with halogen, hydroxyl, cycloalkyl, amino, non-aromatic heterocycle, carboxylic acid, phosphonic acid, sulphonic acid or phosphoric acid, unless otherwise specified;or an enantiomer, diastereoisomer, hydrate, solvate, crystal form, isomer or tautomer thereof;or a pharmaceutically acceptable salt of any of the foregoing, wherein the disorder is selected from the group consisting of inflammatory bowel disease and ulcerative colitis. |
