Design and optimisation of potent gp120-CD4 inhibitors.
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.
Tran
Thien-Duc
TD
Discovery Chemistry, Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich, Kent, UK. thien.tran@pfizer.com
Adam
Fiona M
FM
Calo
Frederick
F
Fenwick
David R
DR
Fok-Seang
Juin
J
Gardner
Iain
I
Hay
Duncan A
DA
Perros
Manos
M
Rawal
Jaiessh
J
Middleton
Donald S
DS
Parkinson
Tanya
T
Pickford
Christopher
C
Platts
Michelle
M
Randall
Amy
A
Stephenson
Peter T
PT
Vuong
Hannah
H
Williams
David H
DH
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
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D023581:HIV Fusion Inhibitors; D007546:Isoquinolines; D009539:Nicotinic Acids