Novel lopinavir analogues incorporating heterocyclic replacements of six-member cyclic urea--synthesis and structure-activity relationships.
The HIV protease inhibitor ABT-378 (lopinavir) has a six-member cyclic urea in the P-2 position. A series of analogues in which the six-member cyclic urea is replaced by various heterocycles was synthesized and the structure-activity relationships explored.
Sham
Hing L
HL
Pharmaceutical Discovery, R4MA Building AP-10, Abbott Laboratories, Abbott Park, IL 60064-6101, USA. hing.l.sham@abbott.com
Betebenner
David A
DA
Rosenbrook
William
W
Herrin
Thomas
T
Saldivar
Ayda
A
Vasavanonda
Sudthida
S
Plattner
Jacob J
JJ
Norbeck
Daniel W
DW
D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000737:chemistry; D006801:Humans; D061466:Lopinavir; D008826:Microbial Sensitivity Tests; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014508:Urea / Q000737:chemistry
D004791:Enzyme Inhibitors; D017320:HIV Protease Inhibitors; D006571:Heterocyclic Compounds; D011744:Pyrimidinones; D061466:Lopinavir; D014508:Urea