New immunosuppressive and antiinflammatory FR520 derivs. - for treating e.g. transplant resistance, rheumatoid arthritis, multiple sclerosis, diabetes, etc.

摘要

New polyhydroxy-19,22-O-furan-FR520 derivs. are of formula (I) where R2 = Me, Et, n-propyl or allyl; and R3 = OH or OMe. (I) are made by treating the epoxide of partial formula (II), opt. 33-OH protected, with HF. Typically (II) is dissolved in e.g. MeCN, treated with aq. HF and the mixt. stirred for about 8 hr. at room temp.. USE/ADVANTAGE - (I) have immunosuppressive, antiinflammatory and antiproliferative activities, so are useful e.g. for treating organ transplant rejection; rheumatoid arthritis, multiple sclerosis; myasthemia gravis; dermatitis; acne, etc.. They are admin. topically (at a concn. of 1-3%) or systemically at 0.15-1.5 mg/kg/day. (I) also improve activity, effect and/or sensitivity of chemotherapeutic agents, esp. to reduce the normal dose of toxic antineplastic and cytostatic agents.