Discovery and characterization of potent and selective 4-oxo-4-(5-(5-phenyl-1,2,4-oxadiazol-3-yl)indolin-1-yl)butanoic acids as S1P₁ agonists

Bioorg Med Chem Lett. 2011 Oct 1;21(19):6013-8. doi: 10.1016/j.bmcl.2011.05.110. Epub 2011 Jun 6.

Abstract

S1P(1) receptor driven lymphopenia has proven utility in the treatment of an array of autoimmune disease states. As a part of our efforts to develop potent and selective S1P(1) receptor agonists, we have identified a novel chemical series of 4-oxo-4-(5-(5-phenyl-1,2,4-oxadiazol-3-yl)indolin-1-yl)butanoic acid S1P(1) receptor agonists.

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy*
  • Butyrates / chemical synthesis*
  • Butyrates / pharmacokinetics
  • Butyrates / pharmacology*
  • Disease Models, Animal
  • Dogs
  • Dose-Response Relationship, Drug
  • Drug Discovery
  • Drug Evaluation, Preclinical
  • Haplorhini
  • High-Throughput Screening Assays
  • Humans
  • Immunosuppressive Agents / chemical synthesis*
  • Immunosuppressive Agents / pharmacokinetics
  • Immunosuppressive Agents / pharmacology*
  • Indoles / chemical synthesis*
  • Indoles / pharmacokinetics
  • Indoles / pharmacology*
  • Lymphocytes / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nerve Tissue Proteins / agonists*
  • Nerve Tissue Proteins / chemistry
  • Oxadiazoles / chemical synthesis*
  • Oxadiazoles / pharmacokinetics
  • Oxadiazoles / pharmacology*
  • RNA-Binding Proteins / agonists*
  • RNA-Binding Proteins / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Butyrates
  • GEMIN2 protein, human
  • Immunosuppressive Agents
  • Indoles
  • Nerve Tissue Proteins
  • Oxadiazoles
  • RNA-Binding Proteins