HYDROXYALKYLAMMONIUM-PYRIMIDINES OR PURINES AND NUCLEOSIDE DERIVATIVES, USEFUL AS INHIBITORS OF INFLAMMATORY CYTOKINES

摘要

Novel hydroxyalkylammonium-pyrimidine and nucleoside derivatives (I) have been found to be useful as inhibitors of inflammatory cytokines. They can be used, inter alia, in the therapy of septic shock, cachexia, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis and AIDS. The compounds are typically prepared by reaction of an iodo substituted nucleoside with the appropriately substituted hydroxyalkylamine, wherein R is a group of formula (a) wherein R1 is one or two lower alkyl groups with the proviso that when two lower alkyl groups are present, then the nitrogen atom is quaternized; R2 is hydrogen or an alkanoyl group of 2-20 carbon atoms; n is 2-6; or R is a substituted furanyl group of formula (b) wherein n, R1 and R2 are as hereinbefore defined; and the wavy lines indicate either stereochemical configuration; R' and R'' are independently hydrogen, halogen or a lower alkyl, lower alkenyl, lower alkynyl, or aralkyl group; R''' is hydrogen, halogen, alkylthio, amino, acylamino carbamyl or azide; and the pharmaceutically acceptable salts thereof.