5442-46-6Relevant academic research and scientific papers
Identification of a Novel Oxadiazole Inhibitor of Mammalian Target of Rapamycin
Lim, Sunwoo,Lee, Hyomin,Kim, Euijung,Hur, Wooyoung
, p. 296 - 303 (2020/02/04)
We performed a biochemical screen against mTOR using in-house small molecule library. Two novel, structurally distinct hits were identified. Among them, a novel oxadiazole scaffold compound (2) suppressed the phosphorylation of both S6K1 and Akt1 in HeLa cells. Docking study suggested that 2 is ATP-competitive and shows a pi-pi interaction with Trp2239 and hydrogen bonds with Trp2239 and Thr2245. Through derivatization, a slightly more potent analogue (2a) was identified with IC50 of 9.6 μM. Our study provides a starting point for discovery of novel potent mTOR inhibitors.
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.
Efficient methods for the synthesis of 2-hydroxyphenazine based on the Pd-catalyzed N-arylation of aryl bromides
Tietze, Mario,Iglesias, Alberto,Merisor, Elena,Conrad, Juergen,Klaiber, Iris,Beifuss, Uwe
, p. 1549 - 1552 (2007/10/03)
(Chemical Equation Presented) Substituted diphenylamines can be synthesized by Pd(0)-catalyzed N-arylation using o-nitroanilines and nitro-substituted aryl bromides for a substrate. Cyclization of the diphenylamines by various methods, including the intramolecular Pd(0)-catalyzed N-arylation, produces 2-methoxyphenazine which can easily be deprotected to give 2-hydroxyphenazine. This phenazine is required to synthesize methanophenazine, a novel redoxactive cofactor isolated from methanogenic archaea.
