POTENT IMMUNOSUPPRESSANTS, 2-ALKYL-2-AMINOPROPANE-1,3-DIOLS

Several immunosuppressants, ISP-I ,4-dihydroxy-2-(hydroxymethyl)-14-ox oeicos-6-enoic acid, myriocin = thermozymocidin] and mycestericins A-G , were isolated from culture broths of Isaria sinclairii and Mycelia s terilia, respectively. In order to investigate structure-activity rela tionships, extensive modifications of ISP-I were conducted, and it was established that the fundamental structure possessing the immunosuppr essive activity is a symmetrical 2-alkyl-2-aminopropane-1,3-diol. The tetradecyl, pentadecyl, and hexadecyl derivatives prolonged rat skin a llograft, survival in the combination of LEW donor and F344 recipient and were more effective than cyclosporin A. Among them, 2-amino-2-tetr adecylpropane-1,3-diol hydrochloride, ISP-I-55, showed the lowest toxi city. ISP-I-55 is a promising lead compound for the development of eff ective immunosuppressants for organ transplantations and for the treat ment of autoimmune diseases.