74420-15-8Relevant articles and documents
Discovery of a novel class of covalent dual inhibitors targeting the protein kinases bmx and btk
Forster, Michael,Liang, Xiaojun Julia,Schr?der, Martin,Gerstenecker, Stefan,Chaikuad, Apirat,Knapp, Stefan,Laufer, Stefan,Gehringer, Matthias
, p. 1 - 36 (2020/12/15)
The nonreceptor tyrosine TEC kinases are key regulators of the immune system and play a crucial role in the pathogenesis of diverse hematological malignancies. In contrast to the substantial efforts in inhibitor development for Bruton’s tyrosine kinase (BTK), specific inhibitors of the other TEC kinases, including the bone marrow tyrosine kinase on chromosome X (BMX), remain sparse. Here we present a novel class of dual BMX/BTK inhibitors, which were designed from irreversible inhibitors of Janus kinase (JAK) 3 targeting a cysteine located within the solvent-exposed front region of the ATP binding pocket. Structure-guided design exploiting the differences in the gatekeeper residues enabled the achievement of high selectivity over JAK3 and certain other kinases harboring a sterically demanding residue at this position. The most active compounds inhibited BMX and BTK with apparent IC50 values in the single digit nanomolar range or below showing moderate selectivity within the TEC family and potent cellular target engagement. These compounds represent an important first step towards selective chemical probes for the protein kinase BMX.
Visible-light-promoted oxidative halogenation of (hetero)arenes
Jiang, Xuefeng,Li, Yiming,Lu, Lingling
supporting information, p. 5989 - 5994 (2020/10/18)
Organic halides are critical building blocks that participate in various cross-coupling reactions. Furthermore, they widely exist as natural products and artificial molecules in drugs with important physiological activities. Although halogenation has been well studied, to the best of our knowledge, studies focussing on sensitive systems (e.g.aryl amines) have not been reported. Herein, we describe a compatible oxidative halogenation of (hetero)arenes with air as the oxidant and halide ions as halide sources under ambient conditions (visible light, air, aqueous system, room temperature, and normal pressure). Moreover, this protocol is practically feasible for gram-scale synthesis, showing potential for industrial application.
COMPOUNDS FOR USING IN IMAGING AND PARTICULARLY FOR THE DIAGNOSIS OF NEURODEGENERATIVE DISEASES
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Paragraph 1040; 1041, (2019/07/23)
The invention relates to compounds of formula (II) for using in imaging and particularly for the diagnosis of neurodegenerative diseases