C, 
XiRelevant articles and documents
All total 27 Articles be found
All total 27 Articles be found-
Howk et al.
, p. 1899,1901 (1954)
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Bloom,Breslow,Hauser
, p. 539 (1945)
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New pyrido[3,4-g]quinazoline derivatives as CLK1 and DYRK1A inhibitors: synthesis, biological evaluation and binding mode analysis
Tazarki, Helmi,Zeinyeh, Wael,Esvan, Yannick J.,Knapp, Stefan,Chatterjee, Deep,Schr?der, Martin,Joerger, Andreas C.,Khiari, Jameleddine,Josselin, Béatrice,Baratte, Blandine,Bach, Stéphane,Ruchaud, Sandrine,Anizon, Fabrice,Giraud, Francis,Moreau, Pascale
, p. 304 - 317 (2019)
Cdc2-like kinase 1 (CLK1) and dual specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) are involved in the regulation of alternative pre-mRNA splicing. Dysregulation of this process has been linked to cancer progression and neurodegenerative diseases, making CLK1 and DYRK1A important therapeutic targets. Here we describe the synthesis of new pyrido[3,4-g]quinazoline derivatives and the evaluation of the inhibitory potencies of these compounds toward CDK5, CK1, GSK3, CLK1 and DYRK1A. Introduction of aminoalkylamino groups at the 2-position resulted in several compounds with low nanomolar affinity and selective inhibition of CLK1 and/or DYRK1A. Their evaluation on several immortalized or cancerous cell lines showed varying degree of cell viability reduction. Co-crystal structures of CLK1 with two of the most potent compounds revealed two alternative binding modes of the pyrido[3,4-g]quinazoline scaffold that can be exploited for future inhibitor design.
Preparation method of N,N-diethylenediamine
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Paragraph 0006; 0031; 0034; 0035, (2018/08/04)
The invention belongs to the technical field of chemical synthesis and relates to a preparation method of N,N-diethylenediamine. The preparation method of the N,N-diethylenediamine comprises the following steps: (1) preparing 2-diethylamine-based chloroethane hydrochloride: performing heat-preserving reaction on a chlorinating agent and diethylamine ethanol in a reaction solvent, concentrating a reaction solvent after the heat-preserving reaction, adding low molecular alcohol or ester after concentrating, performing recrystallization to obtain a 2-2-diethylamine-based chloroethane hydrochloride wet product and drying to obtain a 2-diethylamine-based chloroethane hydrochloride dry product; (2) preparing the N,N-diethylenediamine: performing heat-preserving and pressure-maintaining reactionon the 2-diethylamine-based chloroethane hydrochloride and excessive liquid ammonia for more than or equal to 4 hours under the conditions that the pressure is 0 to 10 MPa and the temperature is 10 to100 DEG C, recycling the residual ammonia gas after the reaction, adding alkali into the reaction liquid, performing cooling alkali analysis, separating out the lower layer of alkaline liquid, rectifying an organic layer and collecting the fraction with the temperature of 143 to 148 DEG C, to obtain the N,N-diethylenediamine. The N,N-diethylenediamine prepared according to the method provided bythe invention has the advantages of high yield, high content, simplicity in operation, low raw material cost and the like.
