title: Discovery of a small molecule inhibitor through interference with the gp120-CD4 interaction.
abstract: A series of piperazine derivatives were designed and synthesised as gp120-CD4 inhibitors. SAR studies led to the discovery of potent inhibitors in a cell based anti viral assay represented by compounds 9 and 28. The rat pharmacokinetic and antiviral profiles of selected compounds are also presented.
authors.affiliation: Department of Chemistry, Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich, Kent, UK. David.H.Williams@pfizer.com
authors.forename: David H
authors.initials: DH
authors.lastname: Williams
authors.forename: Fiona
authors.initials: F
authors.lastname: Adam
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
authors.initials: D
authors.lastname: Hay
authors.forename: Rawal
authors.initials: R
authors.lastname: Jaiessh
authors.forename: Donald S
authors.initials: DS
authors.lastname: Middleton
authors.forename: Charles E
authors.initials: CE
authors.lastname: Mowbray
authors.forename: Tanya
authors.initials: T
authors.lastname: Parkinson
authors.forename: Manos
authors.initials: M
authors.lastname: Perros
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: Daniel
authors.initials: D
authors.lastname: Siddle
authors.forename: Peter T
authors.initials: PT
authors.lastname: Stephenson
authors.forename: Thien-Duc
authors.initials: TD
authors.lastname: Tran
authors.forename: Hannah
authors.initials: H
authors.lastname: Vuong
mesh_terms: D000818:Animals; D001682:Biological Availability; D015704:CD4 Antigens / Q000378:metabolism*; D045744:Cell Line, Tumor; 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; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D010879:Piperazines / 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; D010879:Piperazines