Synthesis and evaluation of 2-pyridinone derivatives as specific HIV-1 reverse transcriptase inhibitors. 3. Pyridyl and phenyl analogs of 3-aminopyridin-2(1H)-one.
In an ongoing effort to develop novel nonnucleoside, specific human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitors, a series of 3-[(pyridylmethyl)amino]- and 3-[(phenylmethyl)amino]-2-pyridinone derivatives was synthesized and tested for HIV-1 RT inhibitory activity. The more potent compounds have a 2'-methoxy group and 4'- and/or 5'-aliphatic substituents on the pyridyl and phenyl rings. Several of the more potent compounds were also evaluated for antiviral activity in MT-4 cell culture. From this series of compounds, 3-[N-[(5-ethyl-2-methoxy-6-methyl-3-pyridyl)methyl]amino]-5-ethyl-6- methylpyridin-2(1H)-one (6) was selected for clinical evaluation.
Wai
J S
JS
Merck Research Laboratories, West Point, Pennsylvania 19486.
Williams
T M
TM
Bamberger
D L
DL
Fisher
T E
TE
Hoffman
J M
JM
Hudcosky
R J
RJ
MacTough
S C
SC
Rooney
C S
CS
Saari
W S
WS
Thomas
C M
CM
D000631:Aminopyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D054303:HIV Reverse Transcriptase; D000882:Haplorhini; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D018894:Reverse Transcriptase Inhibitors; D013329:Structure-Activity Relationship
D000631:Aminopyridines; D000998:Antiviral Agents; D011728:Pyridones; D018894:Reverse Transcriptase Inhibitors; C079292:L 702007; D054303:HIV Reverse Transcriptase