Discovery of a small molecule inhibitor through interference with the gp120-CD4 interaction.
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.
Williams
David H
DH
Department of Chemistry, Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich, Kent, UK. David.H.Williams@pfizer.com
Adam
Fiona
F
Fenwick
David R
DR
Fok-Seang
Juin
J
Gardner
Iain
I
Hay
Duncan
D
Jaiessh
Rawal
R
Middleton
Donald S
DS
Mowbray
Charles E
CE
Parkinson
Tanya
T
Perros
Manos
M
Pickford
Christopher
C
Platts
Michelle
M
Randall
Amy
A
Siddle
Daniel
D
Stephenson
Peter T
PT
Tran
Thien-Duc
TD
Vuong
Hannah
H
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
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D023581:HIV Fusion Inhibitors; D010879:Piperazines