Discovery of triazolinone non-nucleoside inhibitors of HIV reverse transcriptase.
Novel non-nucleoside inhibitors of HIV-RT that contain pyridazinone isosteres were prepared, and a series of triazolinones were found to be potent inhibitors of HIV replication. These compounds were active against several NNRTI-resistant virus strains. Pharmacokinetic studies indicated that inhibitor 7e has good bioavailability in rats. Several fragments of inhibitor 7c were prepared, and the binding of these compounds to HIV-RT was analyzed by surface plasmon resonance spectroscopy.
Sweeney
Zachary K
ZK
Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA. zachary.sweeney@roche.com
Acharya
Sahaja
S
Briggs
Andrew
A
Dunn
James P
JP
Elworthy
Todd R
TR
Fretland
Jennifer
J
Giannetti
Anthony M
AM
Heilek
Gabrielle
G
Li
Yu
Y
Kaiser
Ann C
AC
Martin
Michael
M
Saito
Y David
YD
Smith
Mark
M
Suh
Judy M
JM
Swallow
Steven
S
Wu
Jeffrey
J
Hang
Julie Q
JQ
Zhou
Amy S
AS
Klumpp
Klaus
K
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D024882:Drug Resistance, Viral / Q000187:drug effects; D015394:Molecular Structure; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
D019380:Anti-HIV Agents; D011724:Pyridazines; D018894:Reverse Transcriptase Inhibitors; D014230:Triazoles