384835-92-1Relevant academic research and scientific papers
Development of a Scalable Method for Manufacturing the Central Core of CD73 Inhibitor AB680
Fournier, Jeremy,Yan, Xuelei,Tran, Anh T.,Grange, Rebecca L.,Jacob, Steven D.,Kalisiak, Jaroslaw,Lawson, Kenneth V.,Connor, Eric F.,Leleti, Manmohan R.,Powers, Jay P.
, p. 157 - 162 (2021/01/09)
AB680 is a highly potent CD73 small molecule inhibitor discovered and developed by Arcus Biosciences, currently in clinical trials for the treatment of pancreatic cancer. Here, we report the development of a scalable and practical method for the manufacturing of the azaindazole central core. This synthesis features an N-oxide formation followed by an α-chlorination with POCl3 leading to the formation of 4,6-dichloro-1H-pyrazolo[3,4-b]pyridine 1 in high yield and 99.5% UV purity. This method was successfully performed on multikilogram scale to support the synthesis of AB680.
PARENTERALLY ADMINISTERED IMMUNE ENHANCING DRUGS
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Paragraph 0280, (2019/10/01)
Methods of identifying compounds that modulate the conversion of AMP to adenosine by 5'-nucleotidase, ecto, and that possess particular pharmacokinetic characteristics are described herein. Methods of such compounds, and compositions comprising same, for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, are also provided.
MODULATORS OF 5'-NUCLEOTIDASE, ECTO AND THE USE THEREOF
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Paragraph 0350, (2017/08/01)
Compounds that modulate the conversion of AMP to adenosine by 5'- nucleotidase, ecto, and compositions containing the compounds and methods for synthesizing the compounds, are described herein. The use of such compounds and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by 5'-nucleotidase, ecto is also provided.
Lead optimization of spiropyrazolopyridones: A new and potent class of dengue virus inhibitors
Zou, Bin,Chan, Wai Ling,Ding, Mei,Leong, Seh Yong,Nilar, Shahul,Seah, Peck Gee,Liu, Wei,Karuna, Ratna,Blasco, Francesca,Yip, Andy,Chao, Alex,Susila, Agatha,Dong, Hongping,Wang, Qing Yin,Xu, Hao Ying,Chan, Katherine,Wan, Kah Fei,Gu, Feng,Diagana, Thierry T.,Wagner, Trixie,Dix, Ina,Shi, Pei-Yong,Smith, Paul W.
, p. 344 - 348 (2015/03/30)
Spiropyrazolopyridone 1 was identified, as a novel dengue virus (DENV) inhibitor, from a DENV serotype 2 (DENV-2) high-throughput phenotypic screen. As a general trend within this chemical class, chiral resolution of the racemate revealed that R enantiomer was significantly more potent than the S. Cell-based lead optimization of the spiropyrazolopyridones focusing on improving the physicochemical properties is described. As a result, an optimal compound 14a, with balanced in vitro potency and pharmacokinetic profile, achieved about 1.9 log viremia reduction at 3 × 50 mg/kg (bid) or 3 × 100 mg/kg (QD) oral doses in the dengue in vivo mouse efficacy model.
