| abstract |
The invention provides compounds of the general formula LFA-1 / ICAM for use as anti-inflammatory agents, wherein L and K are oxygen or sulfur; Z is nitrogen or = C (R 4b) -; Optionally substituted aryl or heteroaryl; G is a bonding group attached to T or M or absent; J, M and T represent 3-6 membered saturated or partially unsaturated non-aromatic ring-defining groups; R2 is hydrogen, optionally substituted alkyl, -OR12, -NR12R13, -C (= O) R12, -CO2R12, -C (= O) NR12R13, -NR12C (= O) R13, -NR12C (= O) OR13, -S (O) pR13a, -NR12SO2R13a, -SO2NR12R13, cycloalkyl, heterocyclo, aryl or heteroaryl; R4a, R4b and R4c are hydrogen, halogen, optionally substituted alkyl, alkenyl, nitro, cyano, -SR14, -OR14 , -NR 14 R 15, -NR 14 C (= O) R 15, -CO 2 R 14, -C (= O) R 14, -C (= O) NR 14 R 15, aryl, heterocyclo, cycloalkyl or heteroaryl; R3 and R6 are hydrogen, optionally substituted alkyl, alkenyl, hydroxy, alkoxy, aminoalkyl, alkylthio, formyl, acyl, amido, alkoxycarbonyl, sulfonyl, sulfonamido, cycloalkyl , heterocyclo, aryl or heteroaryl; R5, R7 and R8 (i) are hydrogen, halogen, optionally substituted alkyl, alkenyl, nitro, cyano, hydroxy, alkoxy, aminoalkyl, alkylthio, formyl, acyl, carboxy, , amido, alkoxycarbonyl, sulfonyl, sulfonamidyl, cycloalkyl, heterocyclo, aryl or heteroaryl; or (ii) R 7 and R 8 may form a cycloalkane or heterocyclic ring; or (iii) one of R 5 or R 8 may be a chemical bond; R12, R13, R14 and R15 (i) hydrogen, optionally substituted alkyl, cycloalkyl, aryl, heteroaryl or heterocyclo; or (ii) R12 and R13 together and / or R14 and R15 together form a heteroaromatic or heterocyclic ring; R13a is optionally substituted alkyl, cycloalkyl, aryl, heteroaryl or heterocyclo; and p is 1 or 2 -, their enantiomers, diastereomers, pharmaceutically acceptable salts, hydrates, solvates, prodrugs, and pharmaceutical compositions containing them. The invention also relates to intermediates for the preparation of compounds of formula (I). SHE |