Synthesis and antiviral activities of the major metabolites of the HIV protease inhibitor ABT-378 (Lopinavir).
The HIV protease inhibitor ABT-378 (Lopinavir) is metabolized rapidly and extensively by CYP-3A4 catalyzed oxidation. Three of the major metabolites identified were synthesized and their antiviral (HIV) activities determined.
Sham
H L
HL
Pharmaceutical Discovery, D47B, Building AP-10, Abbott Laboratories, Abbott Park, IL 60064-6101, USA. hing.l.sham@abbott.com
Betebenner
D A
DA
Herrin
T
T
Kumar
G
G
Saldivar
A
A
Vasavanonda
S
S
Molla
A
A
Kempf
D J
DJ
Plattner
J J
JJ
Norbeck
D W
DW
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006678:HIV / Q000187:drug effects; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D061466:Lopinavir; D008826:Microbial Sensitivity Tests; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A