title: Design and optimisation of potent gp120-CD4 inhibitors.
abstract: The synthesis and structure-activity relationship of a series of novel gp120-CD4 inhibitors are described. Pharmacokinetic studies and antiviral spectrum assessment of lead compounds led to the identification of compound 36, a potent gp120-CD4 inhibitor which exhibited antiviral potency across a spectrum of 25 clade B isolates.
authors.affiliation: Discovery Chemistry, Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich, Kent, UK. thien.tran@pfizer.com
authors.forename: Thien-Duc
authors.initials: TD
authors.lastname: Tran
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Adam
authors.forename: Frederick
authors.initials: F
authors.lastname: Calo
authors.forename: David R
authors.initials: DR
authors.lastname: Fenwick
authors.forename: Juin
authors.initials: J
authors.lastname: Fok-Seang
authors.forename: Iain
authors.initials: I
authors.lastname: Gardner
authors.forename: Duncan A
authors.initials: DA
authors.lastname: Hay
authors.forename: Manos
authors.initials: M
authors.lastname: Perros
authors.forename: Jaiessh
authors.initials: J
authors.lastname: Rawal
authors.forename: Donald S
authors.initials: DS
authors.lastname: Middleton
authors.forename: Tanya
authors.initials: T
authors.lastname: Parkinson
authors.forename: Christopher
authors.initials: C
authors.lastname: Pickford
authors.forename: Michelle
authors.initials: M
authors.lastname: Platts
authors.forename: Amy
authors.initials: A
authors.lastname: Randall
authors.forename: Peter T
authors.initials: PT
authors.lastname: Stephenson
authors.forename: Hannah
authors.initials: H
authors.lastname: Vuong
authors.forename: David H
authors.initials: DH
authors.lastname: Williams
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D015195:Drug Design; D015699:HIV Envelope Protein gp120 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023581:HIV Fusion Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D015497:HIV-1 / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D009539:Nicotinic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D023581:HIV Fusion Inhibitors; D007546:Isoquinolines; D009539:Nicotinic Acids