An orally bioavailable oxime ether capsid binder with potent activity against human rhinovirus

  • J Med Chem. 2003 Jul 17;46(15):3181-4. doi: 10.1021/jm0202876.
Keith G Watson  1 ,  Renee N Brown ,  Rachel Cameron ,  David K Chalmers ,  Stephanie Hamilton ,  Betty Jin ,  Guy Y Krippner ,  Angela Luttick ,  Darryl B McConnell ,  Phillip A Reece ,  Jane Ryan ,  Pauline C Stanislawski ,  Simon P Tucker ,  Wen-Yang Wu ,  Dale L Barnard ,  Robert W Sidwell
Affiliations
  • 1. Biota Chemistry Laboratory, School of Chemistry, Monash University, PO Box 23 Victoria, Australia 3800. [email protected]
PMID: 12852746 DOI: 10.1021/jm0202876
Abstract

A series of capsid-binding compounds was screened against human rhinovirus (HRV) using a CPE based assay. The ethyl oxime ether 14 was found to have outstanding anti-HRV activity (median IC(50) 4.75 ng/mL), and unlike the equivalent ethyl ester compound 3 (Pirodavir), it has good oral bioavailability, making it a promising development candidate. Compound 14 illustrates that an oxime ether group can act as a metabolically stable bioisostere for an ester functionality.