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. published the artcile< Novel potent and selective pyrazolylpyrimidine-based SYK inhibitors>, Recommanded Product: 1-Chloropyrrolidine-2,5-dione, the main research area is preparation pyrazolyl pyrimidine derivative structure SYK inhibitor; Diamine; Kinase selectivity; SYK.
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.
Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents (potential as). 128-09-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H4ClNO2, Recommanded Product: 1-Chloropyrrolidine-2,5-dione.
Referemce:
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Chlorides – an overview | ScienceDirect Topics