EP0509795A2 — Carbamates of rapamycin

USPTO Abstract

The invention concerns a compound of the structure: wherein R l and R 2 are each, independently, hydrogen, -CONH(CR 3 R 4 ) n -X or CONHSO 2 -Ar; R 3 and R 4 are each independently, hydrogen, alkyl, aralkyl, cycloalkyl of 3-8 carbon atoms, halogen, or trifluoromethyl; providing that when more than one R 3 or R 4 group is present then they may be the same or different; X is hydrogen, lower alkyl, cycloalkyl, trifluoromethyl, nitro, alkoxy, carboalkoxy, aralkyl, halo, dialkylamino, thioalkyl, or Y; Y is a phenyl group which may be optionally mono-, di-, or tri- substituted; Ar is phenyl, naphthyl, pyridyl, quinolyl, isoquinolyl, quinoxalyl, thienyl, thionaphthyl, furyl, benzofuryl, benzodioxyl, benzoxazolyl, benzoisoxazolyl, or benzodioxolyl; wherein the Ar group may be optionally mono-, di-, or tri-subsrituted, and n = 0-5; with the proviso that R 1 and R 2 are not both hydrogen and when n = 0, X is lower alkyl, cycloalkyl , aralkyl, or Y; or a pharmaceutically acceptable salt thereof when X is dialkylamino, when the Ar group contains a basic nitrogen, or when the Ar group is substituted by dialklyamino, SO 3 H, -PO 3 H, or -CO 2 H, which by virtue of its immunosuppressive activity is useful in treating transplantation rejection, host vs. graft disease, autoimmune diseases and discases of inflammation; by virtue of its antitumor activity is useful in treating solid tumors; and by virtue of its antifungal activity is useful in treating fungal infections.