INHIBITORS OF THE FORMATION OF S-CD23 AND THE SECRETION OF TUMOUR NECROSIS FACTOR(TNF)

摘要

PURPOSE: To inhibit the formation of s-CD23 should have twofold action of a) enhancing negative feed back inhibition of IgE synthesis by maintaining level of i-CD(low affinity IgE receptor FceRII, Blast2, 45 kiloDaltons) on surface of B cell, and b) inhibiting the immunostimulatory cytokine activities of higher molecular weight soluble fragments ( Mr37, 33 and 29 kiloDaltons of s-CD23) CONSTITUTION: Compounds of formula (1) wherein R is hydroxy, hydrogen, alkyl, alkenyl, alkynyl or aryl; R¬1 is arylmethyl or heterocyclylmethyl; R¬2 is alkyl, alkenyl, aryl, cycloalkyl or cycloalkenyl; and R¬3 is hydrogen, alkyl, alkenyl, alkynyl of aryl; are potent and selective inhibitors of CD23 processing and TNF release, whilst exhibiting reduce collagenase inhibitory activity in comparison with the compounds already known. These compounds are useful in the treatment of disorders mediated by s-CD23.