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.