title: An orally bioavailable oxime ether capsid binder with potent activity against human rhinovirus.
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.
authors.affiliation: Biota Chemistry Laboratory, School of Chemistry, Monash University, PO Box 23 Victoria, Australia 3800. kwatson@wehi.edu.au
authors.forename: Keith G
authors.initials: KG
authors.lastname: Watson
authors.forename: Renee N
authors.initials: RN
authors.lastname: Brown
authors.forename: Rachel
authors.initials: R
authors.lastname: Cameron
authors.forename: David K
authors.initials: DK
authors.lastname: Chalmers
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hamilton
authors.forename: Betty
authors.initials: B
authors.lastname: Jin
authors.forename: Guy Y
authors.initials: GY
authors.lastname: Krippner
authors.forename: Angela
authors.initials: A
authors.lastname: Luttick
authors.forename: Darryl B
authors.initials: DB
authors.lastname: McConnell
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Reece
authors.forename: Jane
authors.initials: J
authors.lastname: Ryan
authors.forename: Pauline C
authors.initials: PC
authors.lastname: Stanislawski
authors.forename: Simon P
authors.initials: SP
authors.lastname: Tucker
authors.forename: Wen-Yang
authors.initials: WY
authors.lastname: Wu
authors.forename: Dale L
authors.initials: DL
authors.lastname: Barnard
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sidwell
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D002213:Capsid / Q000378:metabolism*; D002460:Cell Line; D004987:Ethers; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D010091:Oximes / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D010880:Piperidines / Q000493:pharmacokinetics / Q000494:pharmacology; D011485:Protein Binding; D011724:Pyridazines / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D012229:Rhinovirus / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D004987:Ethers; D010091:Oximes; D010880:Piperidines; D011724:Pyridazines; C074589:pirodavir