1613148-80-3Relevant articles and documents
Novel benzimidazole derivatives as phosphodiesterase 10A (PDE10A) inhibitors with improved metabolic stability
Chino, Ayaka,Masuda, Naoyuki,Amano, Yasushi,Honbou, Kazuya,Mihara, Takuma,Yamazaki, Mayako,Tomishima, Masaki
, p. 3515 - 3526 (2014/06/23)
In this study, we report the identification of potent benzimidazoles as PDE10A inhibitors. We first identified imidazopyridine 1 as a high-throughput screening hit compound from an in-house library. Next, optimization of the imidazopyridine moiety to improve inhibitory activity gave imidazopyridinone 10b. Following further structure-activity relationship development by reducing lipophilicity and introducing substituents, we acquired 35, which exhibited both improved metabolic stability and reduced CYP3A4 time-dependent inhibition.