Synthesis, antiviral activity and pharmacokinetics of P1/P1' substituted 3-aminoindazole cyclic urea HIV protease inhibitors.
A series of P1/P1' substituted cyclic urea analogues were prepared in an attempt to increase the intra-cellular antiviral potency of the nonsymmetrical 3-aminoindazoles DMP 850 and DMP 851. The effect of alkyl substitution of the P1/P1' residues on cellular antiviral potency, protein binding, resistance profile and pharmacokinetics are described.
Kaltenbach
Robert F
RF
Bristol-Myers Squibb Company, Experimental Station, Wilmington, DE 19880, USA. robert.kaltenbach@bms.com
Patel
Mona
M
Waltermire
Robert E
RE
Harris
Gregory D
GD
Stone
Benjamin R P
BR
Klabe
Ronald M
RM
Garber
Sena
S
Bacheler
Lee T
LT
Cordova
Beverly C
BC
Logue
Kelly
K
Wright
Matthew R
MR
Erickson-Viitanen
Susan
S
Trainor
George L
GL
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004285:Dogs; D004351:Drug Resistance; D006678:HIV / Q000187:drug effects; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives*
C116353:DMP 850; C116354:DMP 851; D017320:HIV Protease Inhibitors; D006576:Heterocyclic Compounds, 4 or More Rings; D014508:Urea