The synthesis and evaluation of cyclic ureas as HIV protease inhibitors: modifications of the P1/P1' residues.
Two series of cyclic ureas modified at the P1/P1' residue were prepared and evaluated for HIV protease inhibition and whole cell antiviral activity. Compounds 8b, 10 (3- and 4-pyridylmethyl analogs) and 6b (4-methoxy analog) showed significant improvement in antiviral activity relative to lead compounds DMP323 and DMP 450.
Patel
M
M
Department of Chemical & Physical Sciences, DuPont Merck Pharmaceutical Company, Experimental Station, Wilmington, DE 19880-0500, USA.
Bacheler
L T
LT
Rayner
M M
MM
Cordova
B C
BC
Klabe
R M
RM
Erickson-Viitanen
S
S
Seitz
S P
SP
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D006678:HIV / Q000187:drug effects; D016333:HIV Protease / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007202:Indicators and Reagents; D007700:Kinetics; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000998:Antiviral Agents; D001381:Azepines; D017320:HIV Protease Inhibitors; D007202:Indicators and Reagents; D014508:Urea; D016333:HIV Protease; C085816:DMP 323; C099851:DMP 450