Synthesis and antiviral activity of P1' arylsulfonamide azacyclic urea HIV protease inhibitors.
A series of novel azacyclic urea HIV protease inhibitors bearing a benzenesulfonamide group at P1' were synthesized utilizing a parallel synthesis method. Structural studies of early analogs bound in the enzyme active site were used to design more potent inhibitors. The effects of substituting the P1' benzenesulfonyl group on antiviral activity and protein binding are described.
Huang
Peggy P
PP
Abbott Laboratories, Infectious Disease Research, Dept. R47D, Building AP52N, 200 Abbott Park Road, Abbott Park, IL 60064-6217, USA. peggy.huang@abbott.com
Randolph
John T
JT
Klein
Larry L
LL
Vasavanonda
Sudthida
S
Dekhtyar
Tatyana
T
Stoll
Vincent S
VS
Kempf
Dale J
DJ
D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D017320:HIV Protease Inhibitors; D013449:Sulfonamides; D014508:Urea