SINGINGIN-1-PHOSPHATE (S1P) RECEPTOR MODULATORS AND THEIR APPLICATION FOR TREATING MUSCULAR TISSUE INFLAMMATION

摘要

1. The use of an S1P receptor modulator of formula Ia:! ! where A is —C (O) OR5, —OP (O) (OR5) 2, —P (O) (OR5) 2, —S (O) 2OR5, —P (O) (R5) OR5 or 1H-tetrazole -5-yl, R5 is H or C1-C6 alkyl,! W is a bond, C1-C3 alkylene or C2-C3 alkenylene,! Y is C6-C10 aryl or C2-C9 heteroaryl, for example C3-C9 heteroaryl, optionally containing 1 to 3 substituents selected from halogen, —OH, —NO2, C1-C6 alkyl, C1-C6 alkoxy groups, halogen-substituted C1-C6 alkyl and halogen -C6 alkoxy group,! Z choose from:! ; ; ; ; ; ! ; ; ; ; ; ! ; ; ; ; ; ! ; ; ; ; ! ; ; ; ; ! and; ! where the left and right asterisks indicate the bond through which the substituent Z is attached to the residue -C (R3) (R4) - and to the residue A of the formula Ia, respectively, R6 is selected from hydrogen and C1-C6 alkyl, and J1 and J2 are independently methylene or a heteroatom selected from S, O and NR5, where R5 is selected from hydrogen and C1-C6 alkyl, and also any alkylene Z may contain one to three substituents selected from a halogen, hydroxy group, C1-C6 alkyl, or R6 is attached to a carbon atom in the composition of residue Y with the formation of a 5-7 membered cycle, for example, a heterocyclic group, specified in patent application WO 04/103306 A, for example, azetidine,! R1 is C6-C10 aryl or C2-C9 heteroaryl, for example C3-C9 heteroaryl, optionally substituted with C1-C6 alkyl, C6-C10 aryl, C6-C10 aryl (C1-C4) alkyl, C3-C9 heteroaryl, C3-C9 heteroaryl (C1-C4) C3-C8 cycloalkyl, C3-C8 cycloalkyl (C1-C4) alkyl, C3-C8 heterocycloalkyl or C3-C8 heterocycloalkyl (C1-C4) alkyl, where any aryl, heteroaryl, cycloalkyl or heterocycloalkyl in the composition of R1 may contain from 1 to 5 from halogen, C1-C6 alkyl, C1-C6 alkoxy groups and halogen-substituted C1-C6 alkyl or C1-C6 alkoxy groups, and any alk