Discovery of MK-1439, an orally bioavailable non-nucleoside reverse transcriptase inhibitor potent against a wide range of resistant mutant HIV viruses

Unusual (+/–)‐electrospray ionization induced fragmentation: Structural elucidation of an in‐process synthetic intermediate of doravirine (MK‐1439) using liquid chromatography/high‐resolution tandem mass spectrometry and two‐dimensional nuclear magnetic resonance

“…Doravirine ( 1 ) (Scheme ) is a human immunodeficiency type 1 virus (HIV‐1) nonnucleoside reverse transcriptase inhibitor (NNRTI) . It is currently in phase III clinical trials as a next‐generation NNRTI with the potential to offer an improved balance of safety, tolerability, efficacy, and simplicity of administration over the current standard of care .…”

“…It is currently in phase III clinical trials as a next‐generation NNRTI with the potential to offer an improved balance of safety, tolerability, efficacy, and simplicity of administration over the current standard of care . The synthetic route to doravirine ( 1 ) is being optimized to support various stages of clinical development with a goal of defining the best commercial route . An understanding of the key impurities generated in the preparation of doravirine is critical for the development of a robust commercial synthesis.…”

“…of doravirine (1) involved the synthesis of pyridone 4 starting from the diene 3. [7] During the reaction, the concentration of intermediate 2 was found to be first increased then gradually decreased with the addition of NH 3 to give product 4.…”

Investigational reverse transcriptase inhibitors for the treatment of HIV

“…Additional advantages of this novel NNRTI include its appreciable water solubility and favorable pharmacokinetic profile [26]. In preclinical studies, conducted in rats and dogs, MK-1439 demonstrated a significantly higher systemic exposure compared to its parent lead compound.…”

Design, Synthesis and Insecticide Activity of Novel Acetylcholinesterase Inhibitors: Triazolinone and Phthalimide Heterodimers

“…17,18) 1,2,4-Triazole derivatives, especially triazolinone compounds, exhibited extraordinary activities and were used as agrochemicals, for examples: azafenidin, amicarbazone, sulfentrazone and carfentrazoneethyl. They also showed exciting biological activities such as anti-inflammatory, 19,20) anti-human immunodeficiency virus (HIV) activities, 21,22) and AChE inhibitory activities. 12,[23][24][25] Another nitrogen-containing heterocycle compounds-phthalimide derivatives, also possessed surprising anti-inflammatory, 20) anti-cancer, 26) antimalarial 23,27) and AChE inhibitory activities.…”