Potent immunosuppressants, 2-alkyl-2-aminopropane-1,3-diols

J Med Chem. 1996 Oct 25;39(22):4451-9. doi: 10.1021/jm960391l.


Several immunosuppressants, ISP-I [(2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2-(hydroxymethyl)-14-oxoeicos++ +-6-enoic acid, myriocin = thermozymocidin] and mycestericins A-G, were isolated from culture broths of Isaria sinclairii and Mycelia sterilia, respectively. In order to investigate structure-activity relationships, extensive modifications of ISP-I were conducted, and it was established that the fundamental structure possessing the immunosuppressive activity is a symmetrical 2-alkyl-2-aminopropane-1,3-diol. The tetradecyl, pentadecyl, and hexadecyl derivatives prolonged rat skin allograft survival in the combination of LEW donor and F344 recipient and were more effective than cyclosporin A. Among them, 2-amino-2-tetradecylpropane-1,3-diol hydrochloride, ISP-I-55, showed the lowest toxicity. ISP-I-55 is a promising lead compound for the development of effective immunosuppressants for organ transplantations and for the treatment of autoimmune diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / metabolism
  • Alkylation
  • Animals
  • Ascomycota
  • Eicosanoic Acids / chemistry
  • Fatty Acids, Monounsaturated / chemistry*
  • Fatty Acids, Unsaturated / chemistry
  • Immunosuppressive Agents / chemical synthesis*
  • Interleukin-2 / biosynthesis
  • Mice
  • Propylene Glycols / chemistry*
  • Rats
  • Serine C-Palmitoyltransferase
  • Skin / drug effects
  • Spleen / drug effects


  • Eicosanoic Acids
  • Fatty Acids, Monounsaturated
  • Fatty Acids, Unsaturated
  • Immunosuppressive Agents
  • Interleukin-2
  • Propylene Glycols
  • mycestericin B
  • mycestericin A
  • mycestericin D
  • mycestericin C
  • Acyltransferases
  • Serine C-Palmitoyltransferase
  • thermozymocidin