Discovery of novel and potent retinoic acid receptor alpha agonists: syntheses and evaluation of benzofuranyl-pyrrole and benzothiophenyl-pyrrole derivatives

J Med Chem. 2000 Jul 27;43(15):2929-37. doi: 10.1021/jm000098s.

Abstract

In the course of our studies on retinoic acid receptor (RAR) agonists, we have designed and synthesized a series of benzofuran and benzothiophene derivatives. Some of these compounds (1a,b,e,f,j) markedly inhibited LPS-induced B-lymphocyte proliferation and exerted RARalpha selectivity. One of them, 4-[5-(4,7-dimethylbenzofuran-2-yl)pyrrol-2-yl]benzoic acid (1b), when orally administered significantly inhibited mouse antibody production and delayed type hypersensitivity (DTH) responses from a dose of 0.1 mg/kg.

MeSH terms

  • Administration, Oral
  • Animals
  • Antibody Formation / drug effects
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects*
  • Cell Division / drug effects
  • Escherichia coli
  • Female
  • Furans / chemical synthesis*
  • Furans / chemistry
  • Furans / pharmacology
  • Hypersensitivity, Delayed / drug therapy
  • Immunosuppressive Agents / chemical synthesis*
  • Immunosuppressive Agents / chemistry
  • Immunosuppressive Agents / pharmacology
  • In Vitro Techniques
  • Lipopolysaccharides
  • Mice
  • Mice, Inbred BALB C
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Pyrroles / pharmacology
  • Receptors, Retinoic Acid / agonists*
  • Retinoic Acid Receptor alpha
  • Structure-Activity Relationship

Substances

  • Furans
  • Immunosuppressive Agents
  • Lipopolysaccharides
  • Pyrroles
  • Rara protein, mouse
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • ER 38925