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.
Purakkattle Biju  1 ,  Kevin McCormick ,  Robert Aslanian ,  Michael Berlin ,  Daniel Solomon ,  Richard Chapman ,  Robbie McLeod ,  Daniel Prelusky ,  Stephen Eckel ,  George Kelly ,  Michelle Natiello ,  Aileen House ,  Xiomara Fernandez ,  Rema Bitar ,  Jonathan Phillips ,  John Anthes
Affiliations
  • 1. Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. [email protected]
PMID: 21944381 DOI: 10.1016/j.bmcl.2011.08.108
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.