19056-40-7Relevant articles and documents
Regioselective chlorination and bromination of unprotected anilines under mild conditions using copper halides in ionic liquids
Wang, Han,Wen, Kun,Nurahmat, Nurbiya,Shao, Yan,Zhang, He,Wei, Chao,Li, Ya,Shen, Yongjia,Sun, Zhihua
, p. 744 - 748 (2012)
By using ionic liquids as solvents, the chlorination or bromination of unprotected anilines at the para-position can be achieved in high yields with copper halides under mild conditions, without the need for potentially hazardous operations such as supplementing oxygen or gaseous HCl.
Preparation method for 2,5-dibromophenol
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, (2019/02/21)
The invention discloses an industrial preparation method for 2,5-dibromophenol. The industrial preparation method for the 2,5-dibromophenol comprises the following steps: using 2-amino-5-nitrobenzenemethyl ether as an initial raw material, and synthesizing the 2,5-dibromophenol through a four-step reaction of performing diazotization bromination, reduction, secondary diazotization bromination anddemethylation. The obtained 2,5-dibromophenol is a black solid, the purity is 97.5%, a raw material conversion rate in each step reaches 100% respectively, and a total yield of the whole process reaches 34%.
Balancing potency, metabolic stability and permeability in pyrrolopyrimidine-based EGFR inhibitors
Han, Jin,Henriksen, Silje,N?rsett, Kristin G.,Sundby, Eirik,Hoff, B?rd Helge
supporting information, p. 583 - 607 (2016/09/14)
The present study describes our continuous effort to develop epidermal growth factor receptor (EGFR) inhibitors based on the 6-aryl-pyrrolo[2,3-d]pyrimidin-4-amine scaffold. The activity-ADME space has been evaluated by synthesizing 43 new structures, including four variations of the 4-amino group and 34 different substitution patterns in the 6-aryl moiety. Most of the new pyrrolopyrimidines were highly active, with twelve analogues possessing lower IC50values than the commercial drug Erlotinib in enzymatic assays. Ten EGFR inhibitors were also profiled in cell studies using the Ba/F3-EGFRL858Rreporter cells, and all revealed nanomolar activity. However, some of the privileged structures in terms of potency had ADME short-comings: compounds containing amides, sulfonamides, amine and hydroxymethyl substituents in the 6-aryl group had low permeability and high efflux, derivatives having (R)-3-amino-3-phenylpropan-1-ol at C-4 induced hERG inhibition properties, and metabolic lability was seen for compounds having (S)-2-methoxy-1-phenylethan-1-amine at C-4. Based on a trade-off between enzymatic activity, cellular potency and ADME properties, (S)-2-phenyl-2-((6-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethan-1-ol appeared as the most promising drug candidate. Cellular studies indicate this compound to have therapeutic use in EGFR driven diseases.