Potent immunosuppressive C32-O-arylethyl ether derivatives of ascomycin with reduced toxicity

Bioorg Med Chem Lett. 1999 Jul 19;9(14):2089-94. doi: 10.1016/s0960-894x(99)00336-4.

Abstract

The synthesis of C32-O-arylethyl ether derivatives of ascomycin that possess equivalent immunosuppressant activity but reduced toxicity, compared to FK-506, is described.

MeSH terms

  • Administration, Oral
  • Animals
  • Calcineurin Inhibitors
  • Drug Evaluation, Preclinical
  • Hypothermia / chemically induced
  • Immunophilins / metabolism
  • Immunosuppressive Agents / chemical synthesis*
  • Immunosuppressive Agents / metabolism
  • Immunosuppressive Agents / pharmacology*
  • Immunosuppressive Agents / toxicity
  • Inhibitory Concentration 50
  • Injections, Intravenous
  • Kidney Diseases / chemically induced
  • Macrolides / chemical synthesis*
  • Macrolides / pharmacology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship
  • T-Lymphocytes / drug effects
  • Tacrolimus / analogs & derivatives*
  • Tacrolimus / chemistry
  • Tacrolimus / pharmacology
  • Tacrolimus / toxicity
  • Tacrolimus Binding Proteins
  • Toxicity Tests

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Macrolides
  • immunomycin
  • Tacrolimus Binding Proteins
  • Immunophilins
  • Tacrolimus