19563-04-3Relevant articles and documents
Novel Allosteric Inhibitors of Deoxyhypusine Synthase against Malignant Melanoma: Design, Synthesis, and Biological Evaluation
Li, Shuai,Li, Xin-Yang,Li, Yu-Heng,Lin, Qi-Qi,Liu, Kai-Li,Meng, Fan-Hao,Qian, Xin-Hua,Wang, De-Pu,Xue, Wen-Han
, p. 13356 - 13372 (2021/09/20)
Based on the novel allosteric site of deoxyhypusine synthase (DHPS), two series of 30 novel 5-(2-methoxyphenoxy)-2-phenylpyrimidin-4-amine derivatives as DHPS inhibitors were designed and synthesized. Among them, compound8m, with the best DHPS inhibitory potency (IC50= 0.014 μM), exhibited excellent inhibition against melanoma cells, which was superior to that of GC7. Besides, molecular docking and molecular dynamics (MD) simulations further proved that compound8mwas tightly bound to the allosteric site of DHPS. Flow cytometric analysis and enzyme-linked immunosorbent assay (ELISA) showed that compound8mcould inhibit the intracellular reactive oxygen species (ROS) level. Furthermore, by western blot analysis, compound8meffectively activated caspase 3 and decreased the expressions of GP-100, tyrosinase, eIF5A2, MMP2, and MMP9. Moreover, both Transwell analysis and wound healing analysis showed that compound8mcould inhibit the invasion and migration of melanoma cells. In thein vivostudy, the tumor xenograft model showed that compound8meffectively inhibited melanoma development with low toxicity.
Preparation technique of dabigatran methanesulfonate
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Paragraph 0069; 0070, (2016/10/10)
The invention discloses a preparation technique of dabigatran methanesulfonate. The technique comprises the following steps: 1) by using a compound I and glycine as raw materials, carrying out condensation and salification to obtain a compound II; 2) by using p-halobenzonitrile (III) as a raw material, synthesizing p-halobenzamidine (IV) under the actions of a catalyst and an aminating agent, and carrying out condensation on the p-halobenzamidine (IV) and n-hexyl chloroacetate to obtain a compound V; and 3) carrying out condensation and salification on the compound V and the compound II to obtain the dabigatran methanesulfonate. The synthesis method has the advantages of mild reaction conditions for each step and high selectivity, and is simple to operate. The dabigatran methanesulfonate has high yield and purity. The technique has the advantages of less discharge of three wastes and environment friendliness, does not need column chromatography purification, and is suitable for industrial production.
TANKYRASE INHIBITORS
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, (2014/06/24)
The present invention relates to a compound of formula I wherein X is C(R6) or N, Y is C or N, and ring A, ring B, R1 and R2 have the meanings defined herein, provided that when ring B is carbocyclic, X is C(R6); or a pharmaceutically acceptable salt or solvate thereof. The compounds are tankyrase-1 and tankyrase-2 inhibitors and are useful in the treatment of a number of conditions, including cancer.
