Tetrahydrocarbazole amides with potent activity against human papillomaviruses

  • Bioorg Med Chem Lett. 2009 Aug 1;19(15):4110-4. doi: 10.1016/j.bmcl.2009.06.001.
Kristjan S Gudmundsson  1 ,  Sharon D Boggs ,  Paul R Sebahar ,  Leah D'Aurora Richardson ,  Andrew Spaltenstein ,  Pamela Golden ,  Phiroze B Sethna ,  Kevin W Brown ,  Kelly Moniri ,  Robert Harvey ,  Karen R Romines
Affiliations
  • 1. Department of Medicinal Chemistry, Infectious Diseases Center of Excellence for Drug Discovery, GlaxoSmithKline Research & Development, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA. [email protected]
PMID: 19556128 DOI: 10.1016/j.bmcl.2009.06.001
Abstract

Synthesis of a series of tetrahydrocarbazole amides with potent activity against human papillomaviruses is described. Synthetic approaches allowing for variation of the substitution pattern of the tetrahydrocarbazole and the amide are outlined and resulting changes in Antiviral activity and certain developability parameters are highlighted. Several compounds with in vitro Antiviral activity (W12 Antiviral assay) in the single digit nanomolar range were identified and N-[(1R)-6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl]-2-pyridinecarboxamide was selected for further evaluation.