Steroidal C-21 mercapto derivatives as dissociated steroids: discovery of an inhaled dissociated steroid

Bioorg Med Chem Lett. 2011 Nov 1;21(21):6343-7. doi: 10.1016/j.bmcl.2011.08.108. Epub 2011 Aug 31.

Abstract

A series of C-21 mercapto derivatives of hydrocortisone have been synthesized and evaluated in cell based transrepression and transactivation assays. The benzothiazole derivative, compound 6 not only showed a dissociated profile in vitro functional assays but also a pharmacological profile in a Brown-Norway rat therapeutic index model of asthma that dissociated side effects (thymolysis) while maintaining efficacy against pulmonary inflammation and lung function.

MeSH terms

  • Administration, Inhalation
  • Animals
  • Asthma / drug therapy
  • Cell Line
  • Drug Discovery
  • Lung / drug effects
  • Rats
  • Steroids / administration & dosage
  • Steroids / chemistry
  • Steroids / pharmacology*
  • Steroids / therapeutic use
  • Structure-Activity Relationship
  • Sulfhydryl Compounds / chemistry*

Substances

  • Steroids
  • Sulfhydryl Compounds