The design and synthesis of diaryl ether second generation HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with enhanced potency versus key clinical mutations.
Using a combination of traditional Medicinal Chemistry/SAR analysis, crystallography, and molecular modeling, we have designed and synthesized a series of novel, highly potent NNRTIs that possess broad antiviral activity against a number of key clinical mutations.
Tucker
Thomas J
TJ
Department of Medicinal Chemistry, Merck Research Laboratories, WP14-3, 770 Sumneytown Pike, PO Box 4, West Point, PA 19486-0004, USA. tom_tucker@merck.com
Saggar
Sandeep
S
Sisko
John T
JT
Tynebor
Robert M
RM
Williams
Theresa M
TM
Felock
Peter J
PJ
Flynn
Jessica A
JA
Lai
Ming-Tain
MT
Liang
Yuexia
Y
McGaughey
Georgia
G
Liu
Meiquing
M
Miller
Mike
M
Moyer
Gregory
G
Munshi
Vandna
V
Perlow-Poehnelt
Rebecca
R
Prasad
Sridhar
S
Sanchez
Rosa
R
Torrent
Maricel
M
Vacca
Joseph P
JP
Wan
Bang-Lin
BL
Yan
Youwei
Y
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015195:Drug Design; D024882:Drug Resistance, Viral; D004987:Ethers / Q000737:chemistry*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D008956:Models, Chemical; D009154:Mutation; D009705:Nucleosides / Q000737:chemistry; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects* / Q000502:physiology
D019380:Anti-HIV Agents; D004987:Ethers; D009705:Nucleosides; D018894:Reverse Transcriptase Inhibitors