Novel potent and selective pyrazolylpyrimidine-based SYK inhibitors was written by Barlaam, Bernard;Boiko, Scott;Boyd, Scott;Dry, Hannah;Gingipalli, Lakshmaiah;Ikeda, Timothy;Johnson, Tony;Kawatkar, Sameer;Lorthioir, Olivier;Pike, Andy;Pollard, Hannah;Read, Jon;Su, Qibin;Wang, Haiyun;Wang, Huimin;Wang, Lianghe;Wang, Peng;Edmondson, Scott D.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2020.Quality Control of 3-Methyl-4-nitro-1H-pyrazole This article mentions the following:
Hybridization of amino-pyrimidine based SYK inhibitors (e.g. 1a) with previously reported diamine-based SYK inhibitors (e.g. TAK-659) led to the identification and optimization of a novel pyrimidine-based series of potent and selective SYK inhibitors, where the original aminomethylene group was replaced by a 3,4-diaminotetrahydropyran group. The initial compound 5 achieved excellent SYK potency. However, it suffered from poor permeability and modest kinase selectivity. Further modifications of the 3,4-diaminotetrahydropyran group were identified and the interactions of those groups with Asp512 were characterised by protein X-ray crystallog. Further optimization of this series saw mixed results where permeability and kinase selectivity were increased and oral bioavailability was achieved in the series, but at the expense of potent hERG inhibition. In the experiment, the researchers used many compounds, for example, 3-Methyl-4-nitro-1H-pyrazole (cas: 5334-39-4Quality Control of 3-Methyl-4-nitro-1H-pyrazole).
3-Methyl-4-nitro-1H-pyrazole (cas: 5334-39-4) belongs to pyrazole derivatives. Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. Pyrazoles can be selectively lithiated at different carbons and subsequently react with electrophiles depending on the substitution patterns.Quality Control of 3-Methyl-4-nitro-1H-pyrazole
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics