SUBSTITUTED LACTOSE AND LACTOSAMINE DERIVATIVES AS CELL ADHESION INHIBITORS

摘要

Simple lactose or lactosamine related compounds which behave as ligands for the ELAM-1 and related receptors are described. These compounds are of formula (1) wherein each R1 is independently H or lower alkyl (1-4C); R2 is H, lower alkyl (1-4C), alkylaryl or one or more additional saccharide residues; R?3 and R4¿ are each independently H, alkyl(1-6C), aryl or R?3 and R4¿, taken together, form a five- or six-membered ring optionally containing a heteroatom selected from the group consisting of O, S, and NR1; wherein said five- or six-membered ring may further be substituted by one or more substituents selected from the group consisting of (CHOR1)mH wherein m is 1-4, OR?1, OOCR1, NR1¿2, NHCOR1, and SR1; Y is H, OR?1, OOCR1, NR1¿2, NCOR?1 or SR1¿; and X is -CHR?5(CHOR1)¿2CHR6OR1 wherein R?5 and R6¿ are each independently H, lower alkyl(1-4C) optionally substituted with one or more F, or result in a five- or six-membered ring optionally containing a heteroatom selected from the group consisting of O, S, and NR1; said five- or six-membered ring optionally substituted with one substituent selected from the group consisting of R1, CH2OR?1, OR1, OOCR1, NR1¿2, NHCOR1, SR1 and F; or X is benzoyl or naphthoyl having 1-3 hydroxyl substituents, with the proviso that if X represents a hexose substituent R?3 and R4¿, taken together, cannot provide a hexose substituent. These compounds are useful in the treatment of conditions characterized by excess inflammation.